Feature

A growing body of evidence has shown that people who regularly take aspirin have a lower risk for colorectal cancer (CRC) and are less likely to die if they do develop the disease.

A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.

The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.

But what, exactly, is aspirin doing?

We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.

“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.

In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.

Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.

Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.

The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).

Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.

The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.

At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.

Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.

The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.

CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.

The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.

“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”

Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.

However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.

PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.

“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”

David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.

Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.

Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.

A version of this article appeared on Medscape.com .

A growing body of evidence has shown that people who regularly take aspirin have a lower risk for colorectal cancer (CRC) and are less likely to die if they do develop the disease.

A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.

The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.

But what, exactly, is aspirin doing?

We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.

“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.

In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.

Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.

Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.

The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).

Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.

The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.

At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.

Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.

The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.

CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.

The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.

“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”

Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.

However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.

PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.

“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”

David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.

Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.

Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.

A version of this article appeared on Medscape.com .

A growing body of evidence has shown that people who regularly take aspirin have a lower risk for colorectal cancer (CRC) and are less likely to die if they do develop the disease.

A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.

The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.

But what, exactly, is aspirin doing?

We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.

“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.

In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.

Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.

Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.

The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).

Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.

The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.

At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.

Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.

The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.

CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.

The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.

“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”

Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.

However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.

PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.

“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”

David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.

Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.

Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.

A version of this article appeared on Medscape.com .

Potential harms and benefits should be weighed carefully before women and their physicians decide on breast cancer screening, according to updated guidelines from the Canadian Task Force on Preventive Health Care.

The draft guidelines stem from a review of more than 165 recent randomized controlled trials, observational studies, mathematical models, and other data.

The guideline working group included four breast cancer experts (a medical oncologist, a radiation oncologist, a surgical oncologist, and a radiologist), three patient partners, six family physicians, a nurse practitioner, evidence review teams, and other experts.

To avoid potential conflicts of interest, the oncologists provided input but did not vote on the final recommendations, Guylène Thériault, MD, a family physician and chair of the task force and Breast Cancer Working Group, said in an interview. 

The guideline recommends that, after the potential benefits and harms of screening have been considered, mammography should be accessible every 2-3 years to women (ie, people assigned female at birth) between ages 40 and 74 years who are at average or moderately increased risk.

Women with a personal or extensive family history of breast cancer or genetic mutations that would increase breast cancer risk; those who have symptoms, such as a lump; those who feel they may be at high risk; and those who are transgender women should consult a healthcare provider about appropriate options, according to the updated guidelines, which do not apply to these patients.

The draft guidelines were published online on May 30 and are open for public comment until August 30.
 

‘Three Big Questions’

To develop the guidelines, the work group asked “three big questions,” said Dr. Thériault. The first was the effectiveness of breast cancer screening for women aged 40 years and over. For this question, this systematic review, unlike the 2018 guideline update, included not only randomized trials but also observational data to ensure that the work group considered all available data.

“The second question was about comparative effectiveness,” which is something the United States considered for the latest US Preventive Services Task Force (USPSTF) update, said Dr. Thériault. The USPSTF asked questions such as “What happens if we start screening patients at age 40 years? Or at age 50 years? What happens if we stop at age 74 years? Or if we use different tests such as 3D versus digital mammography?”

The Canadian Task Force relied on the evidence that the USPSTF found after grading it with its own criteria, she said. The results were similar, and so are the recommendations in this area. “For example, we don’t recommend supplementary screening for women with dense breasts because there are no studies to inform patient-oriented benefits.”

The third question was about the values and preferences of women regarding breast cancer screening, which is something the United States didn’t examine. “We had looked at that issue in 2018, and this time around, even though we expanded the type of studies, we got the same message: That there are differences between women in their 40s and those who are age 50 years and over.”

“The majority of women in their 40s think that the harms outweigh the benefits and are not interested in screening,” said Dr. Thériault. “But when I say the majority, that’s not every woman. So, we had to recognize that there is variability. And the majority, but not all, of women ages 50-74 years thinks the benefits are higher than the harms. That’s why we say in our recommendation that from ages 40 to 74, it’s a personal choice.”
 

Responding to Objections

Not surprisingly, the task force has heard objections to its draft guidelines. The first is that women aged 40-49 years are being denied mammograms, said Michelle Nadler, MD, a medical oncologist at Princess Margaret Cancer Centre in Toronto, Canada. “This [objection] has attained a lot of media coverage, which is unfortunate, because people who have not read the guidelines may believe this is true. The guidelines clearly state that an eligible, informed woman of this age group who wants a screening mammogram should receive one.”

The second commonly heard objection is that the task force is overestimating the harms of screening, such as anxiety and overdiagnosis, she said. But an outcome of “anxiety” was not factored into the guideline. Overdiagnosis was calculated on the basis of the literature, and estimates were converted to a common denominator so that they could be compared, said Dr. Nadler. The same was true of benefits.

Another objection was that screening could mean less need for chemotherapy or full axillary dissection, Dr. Nadler said. However, the task force did not find any primary studies that evaluated these outcomes.

Critics also said that the recommendations do not account for racial or ethnic variations. Although more research is likely needed in this area, “the task force states that individuals should be informed of all of their breast cancer risk factors, including race/ethnicity, and that this should be factored into decisions about screening,” said Dr. Nadler.

“I was very surprised that the task force was accused by some parties of paternalism,” added René Wittmer, MD, adjunct clinical professor of family medicine at the University of Montreal and chair of Choosing Wisely Quebec, Montreal, Canada. “In my opinion, the importance they place on shared decision-making is contrary to medical paternalism and aims to empower women to make a decision that fits with their values and preferences.”

Nevertheless, the inclusion of modeling studies and observational trials “may cause the potential benefits to be amplified, compared with what is seen in randomized controlled trials,” he said in an interview.
 

Decision Aids Help

Once the guidelines are finalized, decision aids will be available to patients and providers to help guide screening discussions, said Dr. Nadler. “Primary care providers need to be aware of an individual’s personal risk factors for breast cancer to know if they are at average, above average, or high lifetime risk of breast cancer. These guidelines do not apply to those with > 20% lifetime risk of breast cancer.”

“The standards for risk communication are in absolute numbers over a common denominator,” she noted. “This is how primary care providers discuss other important primary care topics like smoking cessation, cardiovascular disease (and decisions about statin medications), and osteoporosis risk. These same standards should apply for breast cancer screening.”

Furthermore, she said, providers “should be aware that individuals from marginalized communities may benefit from more than one conversation until they are able to make a decision about screening that is right for them.”

“There is good evidence showing that most advances we’ve seen in breast cancer outcomes (ie, reduction in breast cancer mortality) are likely due to improvements in treatment, not screening,” said Dr. Wittmer. “In fact, mortality reductions are seen even in age groups or countries where there is no routine screening. This means that women benefit from advances in treatments, whether they choose to get screened or not.”
 

‘Mammography Saves Lives’

Commenting on the updated guidelines, Janie Lee, MD, professor of radiology at the University of Washington School of Medicine and director of breast imaging at the Fred Hutchinson Cancer Center, both in Seattle, said: “For the USPSTF, benefits of life years gained were also considered, in addition to breast cancer deaths averted. To save more lives from breast cancer, guidelines may focus on screening women at older ages, when annual rates of breast cancer are higher.” By contrast, when thinking in terms of years of life saved, focusing on screening younger women, who have more years of life left, increases benefits. “Both are important outcomes that we want to improve with effective screening.”

That said, “we should follow the guidelines of our specific national organizations,” she continued. “Overall populations and healthcare systems are different between the US and Canada.”

For example, “the USPSTF specifically highlighted the potential for reducing breast cancer mortality in Black women, who are more likely to develop biologically aggressive tumors that are diagnosed at more advanced stages, when making updated recommendations earlier this year,” she said. “The Canadian guidelines did not make specific recommendations by race or ethnicity group, instead highlighting the need for more research on the impact of screening in these groups.”

In addition, “screening every year versus every other year is more routine in the US compared with Canada,” she noted. And nonmedical factors that influence health and that may influence access to medical care and timely diagnosis of breast cancer “may be different between our two countries.”

“The most important take-home message is that the scientific evidence is strong that screening mammography saves lives,” said Dr. Lee. “These new recommendations will hopefully result in more early diagnoses of breast cancer and save more lives. Screening works best when it’s used regularly, regardless of how frequently you return. Once you start screening, please urge your patients to plan to return.”

Dr. Nadler disclosed speaker honoraria and consulting fees from Novartis and Exact Sciences outside the scope of this interview and innovation funding from the NSH/UHN AMO Innovation Fund Competition for Developing and Implementing a Consensus Recommendation for Breast Cancer Screening Best Practices. Dr. Thériault is chair of the task force and chair of the working group for the draft guidelines. Dr. Wittmer is chair of Choosing Wisely Quebec. Dr. Lee reported no relevant financial relationships related to her interview.

A version of this article appeared on Medscape.com.

Potential harms and benefits should be weighed carefully before women and their physicians decide on breast cancer screening, according to updated guidelines from the Canadian Task Force on Preventive Health Care.

The draft guidelines stem from a review of more than 165 recent randomized controlled trials, observational studies, mathematical models, and other data.

The guideline working group included four breast cancer experts (a medical oncologist, a radiation oncologist, a surgical oncologist, and a radiologist), three patient partners, six family physicians, a nurse practitioner, evidence review teams, and other experts.

To avoid potential conflicts of interest, the oncologists provided input but did not vote on the final recommendations, Guylène Thériault, MD, a family physician and chair of the task force and Breast Cancer Working Group, said in an interview. 

The guideline recommends that, after the potential benefits and harms of screening have been considered, mammography should be accessible every 2-3 years to women (ie, people assigned female at birth) between ages 40 and 74 years who are at average or moderately increased risk.

Women with a personal or extensive family history of breast cancer or genetic mutations that would increase breast cancer risk; those who have symptoms, such as a lump; those who feel they may be at high risk; and those who are transgender women should consult a healthcare provider about appropriate options, according to the updated guidelines, which do not apply to these patients.

The draft guidelines were published online on May 30 and are open for public comment until August 30.
 

‘Three Big Questions’

To develop the guidelines, the work group asked “three big questions,” said Dr. Thériault. The first was the effectiveness of breast cancer screening for women aged 40 years and over. For this question, this systematic review, unlike the 2018 guideline update, included not only randomized trials but also observational data to ensure that the work group considered all available data.

“The second question was about comparative effectiveness,” which is something the United States considered for the latest US Preventive Services Task Force (USPSTF) update, said Dr. Thériault. The USPSTF asked questions such as “What happens if we start screening patients at age 40 years? Or at age 50 years? What happens if we stop at age 74 years? Or if we use different tests such as 3D versus digital mammography?”

The Canadian Task Force relied on the evidence that the USPSTF found after grading it with its own criteria, she said. The results were similar, and so are the recommendations in this area. “For example, we don’t recommend supplementary screening for women with dense breasts because there are no studies to inform patient-oriented benefits.”

The third question was about the values and preferences of women regarding breast cancer screening, which is something the United States didn’t examine. “We had looked at that issue in 2018, and this time around, even though we expanded the type of studies, we got the same message: That there are differences between women in their 40s and those who are age 50 years and over.”

“The majority of women in their 40s think that the harms outweigh the benefits and are not interested in screening,” said Dr. Thériault. “But when I say the majority, that’s not every woman. So, we had to recognize that there is variability. And the majority, but not all, of women ages 50-74 years thinks the benefits are higher than the harms. That’s why we say in our recommendation that from ages 40 to 74, it’s a personal choice.”
 

Responding to Objections

Not surprisingly, the task force has heard objections to its draft guidelines. The first is that women aged 40-49 years are being denied mammograms, said Michelle Nadler, MD, a medical oncologist at Princess Margaret Cancer Centre in Toronto, Canada. “This [objection] has attained a lot of media coverage, which is unfortunate, because people who have not read the guidelines may believe this is true. The guidelines clearly state that an eligible, informed woman of this age group who wants a screening mammogram should receive one.”

The second commonly heard objection is that the task force is overestimating the harms of screening, such as anxiety and overdiagnosis, she said. But an outcome of “anxiety” was not factored into the guideline. Overdiagnosis was calculated on the basis of the literature, and estimates were converted to a common denominator so that they could be compared, said Dr. Nadler. The same was true of benefits.

Another objection was that screening could mean less need for chemotherapy or full axillary dissection, Dr. Nadler said. However, the task force did not find any primary studies that evaluated these outcomes.

Critics also said that the recommendations do not account for racial or ethnic variations. Although more research is likely needed in this area, “the task force states that individuals should be informed of all of their breast cancer risk factors, including race/ethnicity, and that this should be factored into decisions about screening,” said Dr. Nadler.

“I was very surprised that the task force was accused by some parties of paternalism,” added René Wittmer, MD, adjunct clinical professor of family medicine at the University of Montreal and chair of Choosing Wisely Quebec, Montreal, Canada. “In my opinion, the importance they place on shared decision-making is contrary to medical paternalism and aims to empower women to make a decision that fits with their values and preferences.”

Nevertheless, the inclusion of modeling studies and observational trials “may cause the potential benefits to be amplified, compared with what is seen in randomized controlled trials,” he said in an interview.
 

Decision Aids Help

Once the guidelines are finalized, decision aids will be available to patients and providers to help guide screening discussions, said Dr. Nadler. “Primary care providers need to be aware of an individual’s personal risk factors for breast cancer to know if they are at average, above average, or high lifetime risk of breast cancer. These guidelines do not apply to those with > 20% lifetime risk of breast cancer.”

“The standards for risk communication are in absolute numbers over a common denominator,” she noted. “This is how primary care providers discuss other important primary care topics like smoking cessation, cardiovascular disease (and decisions about statin medications), and osteoporosis risk. These same standards should apply for breast cancer screening.”

Furthermore, she said, providers “should be aware that individuals from marginalized communities may benefit from more than one conversation until they are able to make a decision about screening that is right for them.”

“There is good evidence showing that most advances we’ve seen in breast cancer outcomes (ie, reduction in breast cancer mortality) are likely due to improvements in treatment, not screening,” said Dr. Wittmer. “In fact, mortality reductions are seen even in age groups or countries where there is no routine screening. This means that women benefit from advances in treatments, whether they choose to get screened or not.”
 

‘Mammography Saves Lives’

Commenting on the updated guidelines, Janie Lee, MD, professor of radiology at the University of Washington School of Medicine and director of breast imaging at the Fred Hutchinson Cancer Center, both in Seattle, said: “For the USPSTF, benefits of life years gained were also considered, in addition to breast cancer deaths averted. To save more lives from breast cancer, guidelines may focus on screening women at older ages, when annual rates of breast cancer are higher.” By contrast, when thinking in terms of years of life saved, focusing on screening younger women, who have more years of life left, increases benefits. “Both are important outcomes that we want to improve with effective screening.”

That said, “we should follow the guidelines of our specific national organizations,” she continued. “Overall populations and healthcare systems are different between the US and Canada.”

For example, “the USPSTF specifically highlighted the potential for reducing breast cancer mortality in Black women, who are more likely to develop biologically aggressive tumors that are diagnosed at more advanced stages, when making updated recommendations earlier this year,” she said. “The Canadian guidelines did not make specific recommendations by race or ethnicity group, instead highlighting the need for more research on the impact of screening in these groups.”

In addition, “screening every year versus every other year is more routine in the US compared with Canada,” she noted. And nonmedical factors that influence health and that may influence access to medical care and timely diagnosis of breast cancer “may be different between our two countries.”

“The most important take-home message is that the scientific evidence is strong that screening mammography saves lives,” said Dr. Lee. “These new recommendations will hopefully result in more early diagnoses of breast cancer and save more lives. Screening works best when it’s used regularly, regardless of how frequently you return. Once you start screening, please urge your patients to plan to return.”

Dr. Nadler disclosed speaker honoraria and consulting fees from Novartis and Exact Sciences outside the scope of this interview and innovation funding from the NSH/UHN AMO Innovation Fund Competition for Developing and Implementing a Consensus Recommendation for Breast Cancer Screening Best Practices. Dr. Thériault is chair of the task force and chair of the working group for the draft guidelines. Dr. Wittmer is chair of Choosing Wisely Quebec. Dr. Lee reported no relevant financial relationships related to her interview.

A version of this article appeared on Medscape.com.

Potential harms and benefits should be weighed carefully before women and their physicians decide on breast cancer screening, according to updated guidelines from the Canadian Task Force on Preventive Health Care.

The draft guidelines stem from a review of more than 165 recent randomized controlled trials, observational studies, mathematical models, and other data.

The guideline working group included four breast cancer experts (a medical oncologist, a radiation oncologist, a surgical oncologist, and a radiologist), three patient partners, six family physicians, a nurse practitioner, evidence review teams, and other experts.

To avoid potential conflicts of interest, the oncologists provided input but did not vote on the final recommendations, Guylène Thériault, MD, a family physician and chair of the task force and Breast Cancer Working Group, said in an interview. 

The guideline recommends that, after the potential benefits and harms of screening have been considered, mammography should be accessible every 2-3 years to women (ie, people assigned female at birth) between ages 40 and 74 years who are at average or moderately increased risk.

Women with a personal or extensive family history of breast cancer or genetic mutations that would increase breast cancer risk; those who have symptoms, such as a lump; those who feel they may be at high risk; and those who are transgender women should consult a healthcare provider about appropriate options, according to the updated guidelines, which do not apply to these patients.

The draft guidelines were published online on May 30 and are open for public comment until August 30.
 

‘Three Big Questions’

To develop the guidelines, the work group asked “three big questions,” said Dr. Thériault. The first was the effectiveness of breast cancer screening for women aged 40 years and over. For this question, this systematic review, unlike the 2018 guideline update, included not only randomized trials but also observational data to ensure that the work group considered all available data.

“The second question was about comparative effectiveness,” which is something the United States considered for the latest US Preventive Services Task Force (USPSTF) update, said Dr. Thériault. The USPSTF asked questions such as “What happens if we start screening patients at age 40 years? Or at age 50 years? What happens if we stop at age 74 years? Or if we use different tests such as 3D versus digital mammography?”

The Canadian Task Force relied on the evidence that the USPSTF found after grading it with its own criteria, she said. The results were similar, and so are the recommendations in this area. “For example, we don’t recommend supplementary screening for women with dense breasts because there are no studies to inform patient-oriented benefits.”

The third question was about the values and preferences of women regarding breast cancer screening, which is something the United States didn’t examine. “We had looked at that issue in 2018, and this time around, even though we expanded the type of studies, we got the same message: That there are differences between women in their 40s and those who are age 50 years and over.”

“The majority of women in their 40s think that the harms outweigh the benefits and are not interested in screening,” said Dr. Thériault. “But when I say the majority, that’s not every woman. So, we had to recognize that there is variability. And the majority, but not all, of women ages 50-74 years thinks the benefits are higher than the harms. That’s why we say in our recommendation that from ages 40 to 74, it’s a personal choice.”
 

Responding to Objections

Not surprisingly, the task force has heard objections to its draft guidelines. The first is that women aged 40-49 years are being denied mammograms, said Michelle Nadler, MD, a medical oncologist at Princess Margaret Cancer Centre in Toronto, Canada. “This [objection] has attained a lot of media coverage, which is unfortunate, because people who have not read the guidelines may believe this is true. The guidelines clearly state that an eligible, informed woman of this age group who wants a screening mammogram should receive one.”

The second commonly heard objection is that the task force is overestimating the harms of screening, such as anxiety and overdiagnosis, she said. But an outcome of “anxiety” was not factored into the guideline. Overdiagnosis was calculated on the basis of the literature, and estimates were converted to a common denominator so that they could be compared, said Dr. Nadler. The same was true of benefits.

Another objection was that screening could mean less need for chemotherapy or full axillary dissection, Dr. Nadler said. However, the task force did not find any primary studies that evaluated these outcomes.

Critics also said that the recommendations do not account for racial or ethnic variations. Although more research is likely needed in this area, “the task force states that individuals should be informed of all of their breast cancer risk factors, including race/ethnicity, and that this should be factored into decisions about screening,” said Dr. Nadler.

“I was very surprised that the task force was accused by some parties of paternalism,” added René Wittmer, MD, adjunct clinical professor of family medicine at the University of Montreal and chair of Choosing Wisely Quebec, Montreal, Canada. “In my opinion, the importance they place on shared decision-making is contrary to medical paternalism and aims to empower women to make a decision that fits with their values and preferences.”

Nevertheless, the inclusion of modeling studies and observational trials “may cause the potential benefits to be amplified, compared with what is seen in randomized controlled trials,” he said in an interview.
 

Decision Aids Help

Once the guidelines are finalized, decision aids will be available to patients and providers to help guide screening discussions, said Dr. Nadler. “Primary care providers need to be aware of an individual’s personal risk factors for breast cancer to know if they are at average, above average, or high lifetime risk of breast cancer. These guidelines do not apply to those with > 20% lifetime risk of breast cancer.”

“The standards for risk communication are in absolute numbers over a common denominator,” she noted. “This is how primary care providers discuss other important primary care topics like smoking cessation, cardiovascular disease (and decisions about statin medications), and osteoporosis risk. These same standards should apply for breast cancer screening.”

Furthermore, she said, providers “should be aware that individuals from marginalized communities may benefit from more than one conversation until they are able to make a decision about screening that is right for them.”

“There is good evidence showing that most advances we’ve seen in breast cancer outcomes (ie, reduction in breast cancer mortality) are likely due to improvements in treatment, not screening,” said Dr. Wittmer. “In fact, mortality reductions are seen even in age groups or countries where there is no routine screening. This means that women benefit from advances in treatments, whether they choose to get screened or not.”
 

‘Mammography Saves Lives’

Commenting on the updated guidelines, Janie Lee, MD, professor of radiology at the University of Washington School of Medicine and director of breast imaging at the Fred Hutchinson Cancer Center, both in Seattle, said: “For the USPSTF, benefits of life years gained were also considered, in addition to breast cancer deaths averted. To save more lives from breast cancer, guidelines may focus on screening women at older ages, when annual rates of breast cancer are higher.” By contrast, when thinking in terms of years of life saved, focusing on screening younger women, who have more years of life left, increases benefits. “Both are important outcomes that we want to improve with effective screening.”

That said, “we should follow the guidelines of our specific national organizations,” she continued. “Overall populations and healthcare systems are different between the US and Canada.”

For example, “the USPSTF specifically highlighted the potential for reducing breast cancer mortality in Black women, who are more likely to develop biologically aggressive tumors that are diagnosed at more advanced stages, when making updated recommendations earlier this year,” she said. “The Canadian guidelines did not make specific recommendations by race or ethnicity group, instead highlighting the need for more research on the impact of screening in these groups.”

In addition, “screening every year versus every other year is more routine in the US compared with Canada,” she noted. And nonmedical factors that influence health and that may influence access to medical care and timely diagnosis of breast cancer “may be different between our two countries.”

“The most important take-home message is that the scientific evidence is strong that screening mammography saves lives,” said Dr. Lee. “These new recommendations will hopefully result in more early diagnoses of breast cancer and save more lives. Screening works best when it’s used regularly, regardless of how frequently you return. Once you start screening, please urge your patients to plan to return.”

Dr. Nadler disclosed speaker honoraria and consulting fees from Novartis and Exact Sciences outside the scope of this interview and innovation funding from the NSH/UHN AMO Innovation Fund Competition for Developing and Implementing a Consensus Recommendation for Breast Cancer Screening Best Practices. Dr. Thériault is chair of the task force and chair of the working group for the draft guidelines. Dr. Wittmer is chair of Choosing Wisely Quebec. Dr. Lee reported no relevant financial relationships related to her interview.

A version of this article appeared on Medscape.com.

Moving for any new opportunity in medicine can feel like starting a new life, not just a new job. This is especially true for residency or fellowships, as taking a step forward in your career is exciting. But in the process, you may be leaving family and friends for an unknown city or region where you will need to find a community. And the changes could be long-term. According to the Association of American Medical Colleges’ 2023 Report on Residents, 57.1% of the individuals who completed residency training between 2013 and 2022 are still practicing in the state where they completed their residency.

The process of planning out the right timeline; securing a comfortable, convenient, and affordable place to live; and meeting people while working long hours in an unfamiliar location can be overwhelming. And in the case of many residency programs and healthcare settings, financial assistance, relocation information, and other resources are scarce.

This news organization spoke to recent residents and medical school faculty members about how to navigate a medical move and set yourself up for success.
 

1. Find Relocation Resources

First things first. Find out what your program or hospital has to offer.

Some institutions help incoming residents by providing housing options or information. The Icahn School of Medicine at Mount Sinai’s Real Estate Division, for example, provides off-campus housing resources that guide new residents and faculty toward safe, convenient places to live in New York City. It also guarantees on-campus or block-leased housing offers to all incoming residents who apply.

Michael Leitman, MD, FACS, professor of surgery and medical education and dean for Graduate Medical Education at the Icahn School of Medicine at Mount Sinai in New York City, recommends connecting with colleagues at your program for guidance on navigating a new city and a new healthcare setting. He encourages incoming residents to use the contact information they receive during the interview and orientation processes to reach out to co-residents and faculty members.

Other residency programs offer partial reimbursement or need-based financial aid to help with the expense of relocation. But this is unlikely to cover all or even most of the cost of a cross-country move.

When Morgen Owens, MD, moved from Alabama to New York City for a physical medicine and rehabilitation residency at Mount Sinai in 2021, her program offered subsidized housing options. But there was little reimbursement for relocation. She paid around $3000 for a one-way rental truck, gas, one night in a hotel, and movers to unload her belongings. She says driving herself kept the price down because full-service movers would have cost her between $4000 and $6000.

If this will strain your finances, several banks offer loans specifically for medical school graduates to cover residency and internship expenses. But be aware that these loans tend to have higher interest rates than federal student loans because they are based on credit score rather than fixed.
 

2. Reach Out and Buddy Up

Reaching out to more senior residents is essential, and some programs facilitate a buddy system for relocation advice.

Family physician Mursal Sekandari, MD, known as “Dr. Mursi,” attended a residency program at St. Luke’s University Hospital–Bethlehem Campus, in Bethlehem, Pennsylvania. The program’s official buddy system paired her with a senior resident who advised her on the area and gave tips for her apartment search.

On the other hand, when America Revere, MD, moved from Texas to Georgia for a surgery residency, she found that her program offered little relocation assistance, financial or otherwise. She leaned on her co-residents, and especially senior ones, for support while she settled in.

Dr. Revere also discovered the importance of accepting invitations to events hosted by both her fellow residents and her program itself, especially in the early stages of residency. “Accepting social invitations is really the only way to get to know people,” she said. “Sure, you’ll meet people at work and get to know their ‘work’ personalities.” But Dr. Revere’s attendings also threw parties, which she says were a great way to connect with a wider group and build a community.

To meet people both within and beyond her own residency program, Dr. Owens joined a group chat for physical medicine and rehab residents in the New York City area. She suggests looking into GroupMe or WhatsApp groups specific to your specialty.
 

3. Play the ‘Doctor Card’

Finding a place to live in an unfamiliar and competitive housing market can be one of the biggest challenges of any move. Dr. Owens’ options were limited by owning a dog, which wouldn’t be allowed in her hospital’s subsidized housing. Instead, she opted to find her own apartment in New York City. Her strategy: Playing the “doctor card.”

“I explained my situation: ‘I’m a doctor moving from out of state,’ ” Owens said. “Own that! These companies and brokers will look at you as a student and think, ‘Oh, she has no money, she has no savings, she’s got all of these loans, how is she going to pay for this apartment?’ But you have to say, ‘I’m a doctor. I’m an incoming resident who has X amount of years of job security. I’m not going to lose my job while living here.’ ”
 

4. Move Early

Dr. Revere found it important to move into her new home 2 weeks before the start of her residency program. Moving in early allowed her to settle in, get to know her area, neighbors, and co-residents, and generally prepare for her first day. It also gave her time to put furniture together — her new vanity alone took 12 hours.

Having a larger window of time before residency can also benefit those who hire movers or have their furniture shipped. When it comes to a cross-country move, it can take a few days to a few weeks for the truck to arrive — which could translate to a few nights or a few weeks without a bed.

“When residency comes, it comes fast,” Dr. Revere said. “It’s very confusing, and the last thing you need is to have half of your stuff unpacked or have no idea where you are or know nobody around you.”
 

5. Make Your New Home Your Sanctuary

During the stress of residency, your home can be a source of peace, and finding that might require trade-offs.

Dr. Sekandari’s parents urged her to live with roommates to save money on rent, but she insisted that spending more for solitude would be worth it. For her first year of residency, she barely saw her apartment. But when she did, she felt grateful to be in such a tranquil place to ease some of the stress of studying. “If you feel uncomfortable while you’re dealing with something stressful, the stress just exponentially increases,” she said. Creating an environment where you can really relax “makes a difference in how you respond to everything else around you.”

Dr. Revere agrees, urging medical professionals — and particularly residents — to invest in the most comfortable mattresses and bedding they can. Whether you are working nights, she also recommends blackout curtains to help facilitate daytime naps or better sleep in general, especially among the bright lights of bigger cities.

“You’re going to need somewhere to decompress,” she said. “That will look different for everyone. But I would definitely invest in your apartment to make it a sanctuary away from work.”
 

6. Consider a ‘Live’ Stress Reliever

When it comes to crucial stress relief during residency, “I like mine live,” Dr. Revere said in a YouTube vlog while petting her cat, Calyx.

Taking on the added responsibility of a pet during residency or any medical role may seem counterintuitive. But Revere has zero regrets about bringing Calyx along on her journey. “Cats are very easy,” she said. “I have nothing but wonderful things to say about having a cat during my difficult surgical residency.”

Dr. Owens admits that moving to New York City with her dog was difficult during her first years of residency. She worked an average of 80 hours each week and had little time for walks. She made room in her budget for dog walkers. Thankfully, her hours have eased up as she has progressed through her program, and she can now take her dog on longer walks every day. “He definitely has a better life now that I work fewer hours,” she said.

Once you’ve prepared, made the move, and found your village, it’s time for the real work to begin. “The first couple of months are certainly a challenge of adjusting to a new hospital, a new electronic medical record, a new culture, and a new geographic location,” said Dr. Leitman, who has relocated several times. “But at the end of the day ... it’s you and the patient.” By minimizing stress and getting the support you need, it can even be “a fun process,” Dr. Mursi added, “so make it an exciting chapter in your life.”

A version of this article first appeared on Medscape.com.

Moving for any new opportunity in medicine can feel like starting a new life, not just a new job. This is especially true for residency or fellowships, as taking a step forward in your career is exciting. But in the process, you may be leaving family and friends for an unknown city or region where you will need to find a community. And the changes could be long-term. According to the Association of American Medical Colleges’ 2023 Report on Residents, 57.1% of the individuals who completed residency training between 2013 and 2022 are still practicing in the state where they completed their residency.

The process of planning out the right timeline; securing a comfortable, convenient, and affordable place to live; and meeting people while working long hours in an unfamiliar location can be overwhelming. And in the case of many residency programs and healthcare settings, financial assistance, relocation information, and other resources are scarce.

This news organization spoke to recent residents and medical school faculty members about how to navigate a medical move and set yourself up for success.
 

1. Find Relocation Resources

First things first. Find out what your program or hospital has to offer.

Some institutions help incoming residents by providing housing options or information. The Icahn School of Medicine at Mount Sinai’s Real Estate Division, for example, provides off-campus housing resources that guide new residents and faculty toward safe, convenient places to live in New York City. It also guarantees on-campus or block-leased housing offers to all incoming residents who apply.

Michael Leitman, MD, FACS, professor of surgery and medical education and dean for Graduate Medical Education at the Icahn School of Medicine at Mount Sinai in New York City, recommends connecting with colleagues at your program for guidance on navigating a new city and a new healthcare setting. He encourages incoming residents to use the contact information they receive during the interview and orientation processes to reach out to co-residents and faculty members.

Other residency programs offer partial reimbursement or need-based financial aid to help with the expense of relocation. But this is unlikely to cover all or even most of the cost of a cross-country move.

When Morgen Owens, MD, moved from Alabama to New York City for a physical medicine and rehabilitation residency at Mount Sinai in 2021, her program offered subsidized housing options. But there was little reimbursement for relocation. She paid around $3000 for a one-way rental truck, gas, one night in a hotel, and movers to unload her belongings. She says driving herself kept the price down because full-service movers would have cost her between $4000 and $6000.

If this will strain your finances, several banks offer loans specifically for medical school graduates to cover residency and internship expenses. But be aware that these loans tend to have higher interest rates than federal student loans because they are based on credit score rather than fixed.
 

2. Reach Out and Buddy Up

Reaching out to more senior residents is essential, and some programs facilitate a buddy system for relocation advice.

Family physician Mursal Sekandari, MD, known as “Dr. Mursi,” attended a residency program at St. Luke’s University Hospital–Bethlehem Campus, in Bethlehem, Pennsylvania. The program’s official buddy system paired her with a senior resident who advised her on the area and gave tips for her apartment search.

On the other hand, when America Revere, MD, moved from Texas to Georgia for a surgery residency, she found that her program offered little relocation assistance, financial or otherwise. She leaned on her co-residents, and especially senior ones, for support while she settled in.

Dr. Revere also discovered the importance of accepting invitations to events hosted by both her fellow residents and her program itself, especially in the early stages of residency. “Accepting social invitations is really the only way to get to know people,” she said. “Sure, you’ll meet people at work and get to know their ‘work’ personalities.” But Dr. Revere’s attendings also threw parties, which she says were a great way to connect with a wider group and build a community.

To meet people both within and beyond her own residency program, Dr. Owens joined a group chat for physical medicine and rehab residents in the New York City area. She suggests looking into GroupMe or WhatsApp groups specific to your specialty.
 

3. Play the ‘Doctor Card’

Finding a place to live in an unfamiliar and competitive housing market can be one of the biggest challenges of any move. Dr. Owens’ options were limited by owning a dog, which wouldn’t be allowed in her hospital’s subsidized housing. Instead, she opted to find her own apartment in New York City. Her strategy: Playing the “doctor card.”

“I explained my situation: ‘I’m a doctor moving from out of state,’ ” Owens said. “Own that! These companies and brokers will look at you as a student and think, ‘Oh, she has no money, she has no savings, she’s got all of these loans, how is she going to pay for this apartment?’ But you have to say, ‘I’m a doctor. I’m an incoming resident who has X amount of years of job security. I’m not going to lose my job while living here.’ ”
 

4. Move Early

Dr. Revere found it important to move into her new home 2 weeks before the start of her residency program. Moving in early allowed her to settle in, get to know her area, neighbors, and co-residents, and generally prepare for her first day. It also gave her time to put furniture together — her new vanity alone took 12 hours.

Having a larger window of time before residency can also benefit those who hire movers or have their furniture shipped. When it comes to a cross-country move, it can take a few days to a few weeks for the truck to arrive — which could translate to a few nights or a few weeks without a bed.

“When residency comes, it comes fast,” Dr. Revere said. “It’s very confusing, and the last thing you need is to have half of your stuff unpacked or have no idea where you are or know nobody around you.”
 

5. Make Your New Home Your Sanctuary

During the stress of residency, your home can be a source of peace, and finding that might require trade-offs.

Dr. Sekandari’s parents urged her to live with roommates to save money on rent, but she insisted that spending more for solitude would be worth it. For her first year of residency, she barely saw her apartment. But when she did, she felt grateful to be in such a tranquil place to ease some of the stress of studying. “If you feel uncomfortable while you’re dealing with something stressful, the stress just exponentially increases,” she said. Creating an environment where you can really relax “makes a difference in how you respond to everything else around you.”

Dr. Revere agrees, urging medical professionals — and particularly residents — to invest in the most comfortable mattresses and bedding they can. Whether you are working nights, she also recommends blackout curtains to help facilitate daytime naps or better sleep in general, especially among the bright lights of bigger cities.

“You’re going to need somewhere to decompress,” she said. “That will look different for everyone. But I would definitely invest in your apartment to make it a sanctuary away from work.”
 

6. Consider a ‘Live’ Stress Reliever

When it comes to crucial stress relief during residency, “I like mine live,” Dr. Revere said in a YouTube vlog while petting her cat, Calyx.

Taking on the added responsibility of a pet during residency or any medical role may seem counterintuitive. But Revere has zero regrets about bringing Calyx along on her journey. “Cats are very easy,” she said. “I have nothing but wonderful things to say about having a cat during my difficult surgical residency.”

Dr. Owens admits that moving to New York City with her dog was difficult during her first years of residency. She worked an average of 80 hours each week and had little time for walks. She made room in her budget for dog walkers. Thankfully, her hours have eased up as she has progressed through her program, and she can now take her dog on longer walks every day. “He definitely has a better life now that I work fewer hours,” she said.

Once you’ve prepared, made the move, and found your village, it’s time for the real work to begin. “The first couple of months are certainly a challenge of adjusting to a new hospital, a new electronic medical record, a new culture, and a new geographic location,” said Dr. Leitman, who has relocated several times. “But at the end of the day ... it’s you and the patient.” By minimizing stress and getting the support you need, it can even be “a fun process,” Dr. Mursi added, “so make it an exciting chapter in your life.”

A version of this article first appeared on Medscape.com.

Moving for any new opportunity in medicine can feel like starting a new life, not just a new job. This is especially true for residency or fellowships, as taking a step forward in your career is exciting. But in the process, you may be leaving family and friends for an unknown city or region where you will need to find a community. And the changes could be long-term. According to the Association of American Medical Colleges’ 2023 Report on Residents, 57.1% of the individuals who completed residency training between 2013 and 2022 are still practicing in the state where they completed their residency.

The process of planning out the right timeline; securing a comfortable, convenient, and affordable place to live; and meeting people while working long hours in an unfamiliar location can be overwhelming. And in the case of many residency programs and healthcare settings, financial assistance, relocation information, and other resources are scarce.

This news organization spoke to recent residents and medical school faculty members about how to navigate a medical move and set yourself up for success.
 

1. Find Relocation Resources

First things first. Find out what your program or hospital has to offer.

Some institutions help incoming residents by providing housing options or information. The Icahn School of Medicine at Mount Sinai’s Real Estate Division, for example, provides off-campus housing resources that guide new residents and faculty toward safe, convenient places to live in New York City. It also guarantees on-campus or block-leased housing offers to all incoming residents who apply.

Michael Leitman, MD, FACS, professor of surgery and medical education and dean for Graduate Medical Education at the Icahn School of Medicine at Mount Sinai in New York City, recommends connecting with colleagues at your program for guidance on navigating a new city and a new healthcare setting. He encourages incoming residents to use the contact information they receive during the interview and orientation processes to reach out to co-residents and faculty members.

Other residency programs offer partial reimbursement or need-based financial aid to help with the expense of relocation. But this is unlikely to cover all or even most of the cost of a cross-country move.

When Morgen Owens, MD, moved from Alabama to New York City for a physical medicine and rehabilitation residency at Mount Sinai in 2021, her program offered subsidized housing options. But there was little reimbursement for relocation. She paid around $3000 for a one-way rental truck, gas, one night in a hotel, and movers to unload her belongings. She says driving herself kept the price down because full-service movers would have cost her between $4000 and $6000.

If this will strain your finances, several banks offer loans specifically for medical school graduates to cover residency and internship expenses. But be aware that these loans tend to have higher interest rates than federal student loans because they are based on credit score rather than fixed.
 

2. Reach Out and Buddy Up

Reaching out to more senior residents is essential, and some programs facilitate a buddy system for relocation advice.

Family physician Mursal Sekandari, MD, known as “Dr. Mursi,” attended a residency program at St. Luke’s University Hospital–Bethlehem Campus, in Bethlehem, Pennsylvania. The program’s official buddy system paired her with a senior resident who advised her on the area and gave tips for her apartment search.

On the other hand, when America Revere, MD, moved from Texas to Georgia for a surgery residency, she found that her program offered little relocation assistance, financial or otherwise. She leaned on her co-residents, and especially senior ones, for support while she settled in.

Dr. Revere also discovered the importance of accepting invitations to events hosted by both her fellow residents and her program itself, especially in the early stages of residency. “Accepting social invitations is really the only way to get to know people,” she said. “Sure, you’ll meet people at work and get to know their ‘work’ personalities.” But Dr. Revere’s attendings also threw parties, which she says were a great way to connect with a wider group and build a community.

To meet people both within and beyond her own residency program, Dr. Owens joined a group chat for physical medicine and rehab residents in the New York City area. She suggests looking into GroupMe or WhatsApp groups specific to your specialty.
 

3. Play the ‘Doctor Card’

Finding a place to live in an unfamiliar and competitive housing market can be one of the biggest challenges of any move. Dr. Owens’ options were limited by owning a dog, which wouldn’t be allowed in her hospital’s subsidized housing. Instead, she opted to find her own apartment in New York City. Her strategy: Playing the “doctor card.”

“I explained my situation: ‘I’m a doctor moving from out of state,’ ” Owens said. “Own that! These companies and brokers will look at you as a student and think, ‘Oh, she has no money, she has no savings, she’s got all of these loans, how is she going to pay for this apartment?’ But you have to say, ‘I’m a doctor. I’m an incoming resident who has X amount of years of job security. I’m not going to lose my job while living here.’ ”
 

4. Move Early

Dr. Revere found it important to move into her new home 2 weeks before the start of her residency program. Moving in early allowed her to settle in, get to know her area, neighbors, and co-residents, and generally prepare for her first day. It also gave her time to put furniture together — her new vanity alone took 12 hours.

Having a larger window of time before residency can also benefit those who hire movers or have their furniture shipped. When it comes to a cross-country move, it can take a few days to a few weeks for the truck to arrive — which could translate to a few nights or a few weeks without a bed.

“When residency comes, it comes fast,” Dr. Revere said. “It’s very confusing, and the last thing you need is to have half of your stuff unpacked or have no idea where you are or know nobody around you.”
 

5. Make Your New Home Your Sanctuary

During the stress of residency, your home can be a source of peace, and finding that might require trade-offs.

Dr. Sekandari’s parents urged her to live with roommates to save money on rent, but she insisted that spending more for solitude would be worth it. For her first year of residency, she barely saw her apartment. But when she did, she felt grateful to be in such a tranquil place to ease some of the stress of studying. “If you feel uncomfortable while you’re dealing with something stressful, the stress just exponentially increases,” she said. Creating an environment where you can really relax “makes a difference in how you respond to everything else around you.”

Dr. Revere agrees, urging medical professionals — and particularly residents — to invest in the most comfortable mattresses and bedding they can. Whether you are working nights, she also recommends blackout curtains to help facilitate daytime naps or better sleep in general, especially among the bright lights of bigger cities.

“You’re going to need somewhere to decompress,” she said. “That will look different for everyone. But I would definitely invest in your apartment to make it a sanctuary away from work.”
 

6. Consider a ‘Live’ Stress Reliever

When it comes to crucial stress relief during residency, “I like mine live,” Dr. Revere said in a YouTube vlog while petting her cat, Calyx.

Taking on the added responsibility of a pet during residency or any medical role may seem counterintuitive. But Revere has zero regrets about bringing Calyx along on her journey. “Cats are very easy,” she said. “I have nothing but wonderful things to say about having a cat during my difficult surgical residency.”

Dr. Owens admits that moving to New York City with her dog was difficult during her first years of residency. She worked an average of 80 hours each week and had little time for walks. She made room in her budget for dog walkers. Thankfully, her hours have eased up as she has progressed through her program, and she can now take her dog on longer walks every day. “He definitely has a better life now that I work fewer hours,” she said.

Once you’ve prepared, made the move, and found your village, it’s time for the real work to begin. “The first couple of months are certainly a challenge of adjusting to a new hospital, a new electronic medical record, a new culture, and a new geographic location,” said Dr. Leitman, who has relocated several times. “But at the end of the day ... it’s you and the patient.” By minimizing stress and getting the support you need, it can even be “a fun process,” Dr. Mursi added, “so make it an exciting chapter in your life.”

A version of this article first appeared on Medscape.com.

CHICAGO — The landscape of antibody-drug conjugates, or ADCs, continues to grow more crowded in metastatic breast cancer. Indications are expanding, new agents are emerging, combinations with other drug classes are being tested, and many patients with this disease are now receiving more than one ADC.

ADCs use antibodies to bind to the surface proteins of cancer cells to deliver a potent payload of cytotoxic chemotherapy. Three are approved for use in pretreated patients with metastatic breast cancer: sacituzumab govitecan, or SG, for patients with triple-negative disease; trastuzumab deruxtecan, or T-DXd, for patients with HER2-positive and HER2-low disease; and trastuzumab emtansine, or T-DM1, for patients with HER2-positive disease. A fourth agent, datopotamab deruxtecan, or Dato-DXd, is being assessed by the US Food and Drug Administration (FDA) for use in pretreated HR-positive, HER2-negative patients, and others, including sacituzumab tirumotecan, are being tested in clinical trials.At the annual meeting of the American Society of Clinical Oncology, T-DXd (Enhertu, AstraZeneca) showed better progression free survival than chemotherapy in people with HR-positive, HER 2-low metastatic breast cancers. These findings, from the DESTINY Breast-06 trial, were among the most talked-about at ASCO, and are likely to change clinical practice (J Clin Oncol. 2024;42[suppl 17; abstr LBA1000]).

But other ADC results presented at ASCO showed that there is still much to be worked out about the timing and sequencing of these agents, as well as their synergy with other drug classes, in metastatic breast cancer.
 

An ADC gets its first test, and falls short

Antonio Giordano, MD, PhD, of the Dana-Farber Cancer Institute in Boston, presented findings from an open-label phase 2 study of the ADC enfortumab vedotin (EV), an agent currently approved for use in advanced or metastatic urothelial cancer, at ASCO. This study included two cohorts of previously treated metastatic breast cancer patients: one with triple-negative disease (n = 42) and the other with HR-positive HER2-negative (n = 45).

Dr. Giordano and his colleagues’ study is the first to look at this ADC in breast cancer. EV’s antibody targets the cell adhesion molecule Nectin-4.

The researchers found that though EV demonstrated anti-tumor activity in both cohorts — with 19% of the triple-negative patients and 15.6% of the HR-positive/HER2-negative patients responding — the results did not meet the prespecified response thresholds for either cohort. (J Clin Oncol. 2024;42[suppl 16; abstr 1005]).

In an interview, Dr. Giordano said that studies in urothelial cancer had shown better response to EV associated with more expression of Nectin-4, but this study did not see such clear associations between expression and response. While there is no question that Nectin-4 is highly expressed in breast cancer and therefore a viable target, he said, “it may need to be looked at a little more deeply.”

It could also be the case, Dr. Giordano said, that the effect of EV’s payload may have been less robust in participants who had been previously treated with taxane chemotherapy, as nearly all patients in the two cohorts were.

“Taxanes are microtubule disruptors. And with this drug we had a payload with pretty much the same mechanism of action,” Dr. Giordano said. Ideally, he said, he would like to test the agent in a first-line setting, possibly in combination with an immunotherapy agent.

The timing of ADCs is as important as their targets and their payloads — and something that investigators are still struggling to figure out, he said.

A third of the patients in the triple-negative cohort of his study had been previously treated with SG, and a handful of individuals with T-Dxd, he noted.

“We’re in the middle of an ADC revolution,” he said. “It’s really key to figure out the best sequencing for a patient and if it’s actually worth it to do it. Very often we see patients respond best to the first ADC. But sometimes we see patients that do not respond to the first ADC and then they respond to the second one. It’s not very frequent, but it happens.”
 

Hint of Benefit from Adding Immunotherapy to SG

In a separate presentation at ASCO, Ana C. Garrido-Castro, MD, also of the Dana-Farber Cancer Institute, presented results from the SACI-IO HR+ trial, a randomized phase 2 study of SG (Trodelvy, Gilead) with and without pembrolizumab (Keytruda, Merck) in 104 patients with metastatic HR-positive/HER2-negative breast cancer who received prior endocrine therapy and up to one chemotherapy regimen for advanced disease. SACI-IO HR+ is the first randomized trial to report the efficacy of a topoisomerase I-inhibitor ADC with an immune checkpoint inhibitor for the treatment of breast cancer.

The addition of the immune checkpoint inhibitor did not result in a significant improvement in median progression-free survival in the overall population, Dr. Garrido-Castro reported. Median PFS was 8.1 vs 6.2 months with the combination of SG plus pembrolizumab or sacituzumab govitecan alone, respectively. At a median follow-up of 12.5 months, there was also no significant difference seen in median overall survival (OS): 18.5 vs 18.0 months.

About 40% of participants were found to have PD-L1-positive tumors and, among this subgroup, there was a 4.4-month increase in median PFS and 6.0-month increase in median OS with the addition of pembrolizumab to SG, although this did not reach statistical significance. (J Clin Oncol. 2024;42[suppl 17; abstr LBA1004]).

“While the study did not demonstrate a statistically significant benefit with the addition of the immune checkpoint inhibitor to the ADC, there is an interesting signal for potential synergistic activity between the two agents, particularly in those patients with PD-L1 positive tumors,” Dr. Garrido-Castro said in an interview. She noted that the sample sizes for the PD-L1 subgroup were relatively small, and overall survival data are not yet mature.

A separate phase 3 study is looking at the experimental ADC called sacituzumab tirumotecan with and without pembrolizumab compared with chemotherapy in patients with metastatic HR-positive, HER2-negative breast cancer who have received prior endocrine therapy and no prior chemotherapy for metastatic disease, she said.

Similar to SG, sacituzumab tirumotecan is a TROP2-directed ADC with a topoisomerase I-inhibitor payload. With an estimated enrollment of 1,200 patients, this trial may help shed light on whether adding the immune checkpoint inhibitor to the topoisomerase I-inhibitor TROP2-directed ADC improves outcomes in the subgroup of patients with PD-L1 positive tumors, Dr. Garrido-Castro said.
 

Unlocking the Order and Timing of ADCs

Dr. Garrido-Castro is also leading a study that will evaluate the sequential use of ADCs in metastatic breast cancer. That trial, to be called TRADE-DXd, will enroll patients with HER2-low metastatic breast cancer who have received up to one prior line of chemotherapy and no previous topoisomerase I-inhibitors. Participants will receive either T-DXd or Dato-DXd as the first ADC, and then switch to the other ADC (Dato-DXd or T-DXd, respectively) at the time of progression, thus switching the target of the ADC from HER2 to TROP2 or vice versa.

“In real-world practice now, there are patients who receive sequential ADCs, because they are candidates for both,” Dr. Garrido-Castro explained. However, more robust data are needed to refine the selection of the initial antibody drug conjugate and to determine who is more likely to benefit from a second — or maybe even third — ADC.

“One potential mechanism of resistance to antibody drug conjugates is the downregulation of the target of the antibody drug conjugate,” Dr. Garrido-Castro said. “Thus, an important question is, if you modify the target of the ADC, is it possible to overcome that mechanism of resistance?” Another possible mechanism of resistance is to the chemotherapy payload of the ADCs, she said.

Dr. Garrido-Castro’s study will collect tumor samples and blood samples for the purposes of planned correlative analyses to try to better understand the mechanisms that drive response and resistance to these agents.

Dr. Giordano commented that Dr. Garrido-Castro’s study was likely to result in a much better understanding of ADCs and how to use them strategically.

At Dana-Farber, “we collect a lot of samples of patients receiving ADCs. And we are trying to do all kinds of work on circulating tumor DNA, immunohistochemistry expression, and protein expression,” he said. “We are trying to figure out how ADCs really work, and why they stop working.”

Dr. Giordano and colleagues’ study was funded by Astellas Pharma and by Seagen, which was bought by Pfizer in 2023. Dr. Giordano disclosed receiving consulting fees from Pfizer, and several of his coauthors reported relationships with this and other companies. Two were Astellas employees.

Dr. Garrido-Castro and colleagues’ study was funded by Merck and Gilead Sciences. Dr. Garrido-Castro disclosed receiving research support from Gilead Sciences, AstraZeneca, Daiichi Sankyo, Merck, Zenith Epigenetics, Bristol-Myers Squibb, Novartis, Biovica, Foundation Medicine, 4D Path, Precede Biosciences; scientific advisory board/consulting fees from AstraZeneca, Novartis, Daiichi Sankyo; speaker honoraria from AstraZeneca, Daiichi Sankyo; and other support from Roche/Genentech, Gilead Sciences, AstraZeneca, Daiichi Sankyo, Novartis, and Merck, while her coauthors reported similar relationships.

CHICAGO — The landscape of antibody-drug conjugates, or ADCs, continues to grow more crowded in metastatic breast cancer. Indications are expanding, new agents are emerging, combinations with other drug classes are being tested, and many patients with this disease are now receiving more than one ADC.

ADCs use antibodies to bind to the surface proteins of cancer cells to deliver a potent payload of cytotoxic chemotherapy. Three are approved for use in pretreated patients with metastatic breast cancer: sacituzumab govitecan, or SG, for patients with triple-negative disease; trastuzumab deruxtecan, or T-DXd, for patients with HER2-positive and HER2-low disease; and trastuzumab emtansine, or T-DM1, for patients with HER2-positive disease. A fourth agent, datopotamab deruxtecan, or Dato-DXd, is being assessed by the US Food and Drug Administration (FDA) for use in pretreated HR-positive, HER2-negative patients, and others, including sacituzumab tirumotecan, are being tested in clinical trials.At the annual meeting of the American Society of Clinical Oncology, T-DXd (Enhertu, AstraZeneca) showed better progression free survival than chemotherapy in people with HR-positive, HER 2-low metastatic breast cancers. These findings, from the DESTINY Breast-06 trial, were among the most talked-about at ASCO, and are likely to change clinical practice (J Clin Oncol. 2024;42[suppl 17; abstr LBA1000]).

But other ADC results presented at ASCO showed that there is still much to be worked out about the timing and sequencing of these agents, as well as their synergy with other drug classes, in metastatic breast cancer.
 

An ADC gets its first test, and falls short

Antonio Giordano, MD, PhD, of the Dana-Farber Cancer Institute in Boston, presented findings from an open-label phase 2 study of the ADC enfortumab vedotin (EV), an agent currently approved for use in advanced or metastatic urothelial cancer, at ASCO. This study included two cohorts of previously treated metastatic breast cancer patients: one with triple-negative disease (n = 42) and the other with HR-positive HER2-negative (n = 45).

Dr. Giordano and his colleagues’ study is the first to look at this ADC in breast cancer. EV’s antibody targets the cell adhesion molecule Nectin-4.

The researchers found that though EV demonstrated anti-tumor activity in both cohorts — with 19% of the triple-negative patients and 15.6% of the HR-positive/HER2-negative patients responding — the results did not meet the prespecified response thresholds for either cohort. (J Clin Oncol. 2024;42[suppl 16; abstr 1005]).

In an interview, Dr. Giordano said that studies in urothelial cancer had shown better response to EV associated with more expression of Nectin-4, but this study did not see such clear associations between expression and response. While there is no question that Nectin-4 is highly expressed in breast cancer and therefore a viable target, he said, “it may need to be looked at a little more deeply.”

It could also be the case, Dr. Giordano said, that the effect of EV’s payload may have been less robust in participants who had been previously treated with taxane chemotherapy, as nearly all patients in the two cohorts were.

“Taxanes are microtubule disruptors. And with this drug we had a payload with pretty much the same mechanism of action,” Dr. Giordano said. Ideally, he said, he would like to test the agent in a first-line setting, possibly in combination with an immunotherapy agent.

The timing of ADCs is as important as their targets and their payloads — and something that investigators are still struggling to figure out, he said.

A third of the patients in the triple-negative cohort of his study had been previously treated with SG, and a handful of individuals with T-Dxd, he noted.

“We’re in the middle of an ADC revolution,” he said. “It’s really key to figure out the best sequencing for a patient and if it’s actually worth it to do it. Very often we see patients respond best to the first ADC. But sometimes we see patients that do not respond to the first ADC and then they respond to the second one. It’s not very frequent, but it happens.”
 

Hint of Benefit from Adding Immunotherapy to SG

In a separate presentation at ASCO, Ana C. Garrido-Castro, MD, also of the Dana-Farber Cancer Institute, presented results from the SACI-IO HR+ trial, a randomized phase 2 study of SG (Trodelvy, Gilead) with and without pembrolizumab (Keytruda, Merck) in 104 patients with metastatic HR-positive/HER2-negative breast cancer who received prior endocrine therapy and up to one chemotherapy regimen for advanced disease. SACI-IO HR+ is the first randomized trial to report the efficacy of a topoisomerase I-inhibitor ADC with an immune checkpoint inhibitor for the treatment of breast cancer.

The addition of the immune checkpoint inhibitor did not result in a significant improvement in median progression-free survival in the overall population, Dr. Garrido-Castro reported. Median PFS was 8.1 vs 6.2 months with the combination of SG plus pembrolizumab or sacituzumab govitecan alone, respectively. At a median follow-up of 12.5 months, there was also no significant difference seen in median overall survival (OS): 18.5 vs 18.0 months.

About 40% of participants were found to have PD-L1-positive tumors and, among this subgroup, there was a 4.4-month increase in median PFS and 6.0-month increase in median OS with the addition of pembrolizumab to SG, although this did not reach statistical significance. (J Clin Oncol. 2024;42[suppl 17; abstr LBA1004]).

“While the study did not demonstrate a statistically significant benefit with the addition of the immune checkpoint inhibitor to the ADC, there is an interesting signal for potential synergistic activity between the two agents, particularly in those patients with PD-L1 positive tumors,” Dr. Garrido-Castro said in an interview. She noted that the sample sizes for the PD-L1 subgroup were relatively small, and overall survival data are not yet mature.

A separate phase 3 study is looking at the experimental ADC called sacituzumab tirumotecan with and without pembrolizumab compared with chemotherapy in patients with metastatic HR-positive, HER2-negative breast cancer who have received prior endocrine therapy and no prior chemotherapy for metastatic disease, she said.

Similar to SG, sacituzumab tirumotecan is a TROP2-directed ADC with a topoisomerase I-inhibitor payload. With an estimated enrollment of 1,200 patients, this trial may help shed light on whether adding the immune checkpoint inhibitor to the topoisomerase I-inhibitor TROP2-directed ADC improves outcomes in the subgroup of patients with PD-L1 positive tumors, Dr. Garrido-Castro said.
 

Unlocking the Order and Timing of ADCs

Dr. Garrido-Castro is also leading a study that will evaluate the sequential use of ADCs in metastatic breast cancer. That trial, to be called TRADE-DXd, will enroll patients with HER2-low metastatic breast cancer who have received up to one prior line of chemotherapy and no previous topoisomerase I-inhibitors. Participants will receive either T-DXd or Dato-DXd as the first ADC, and then switch to the other ADC (Dato-DXd or T-DXd, respectively) at the time of progression, thus switching the target of the ADC from HER2 to TROP2 or vice versa.

“In real-world practice now, there are patients who receive sequential ADCs, because they are candidates for both,” Dr. Garrido-Castro explained. However, more robust data are needed to refine the selection of the initial antibody drug conjugate and to determine who is more likely to benefit from a second — or maybe even third — ADC.

“One potential mechanism of resistance to antibody drug conjugates is the downregulation of the target of the antibody drug conjugate,” Dr. Garrido-Castro said. “Thus, an important question is, if you modify the target of the ADC, is it possible to overcome that mechanism of resistance?” Another possible mechanism of resistance is to the chemotherapy payload of the ADCs, she said.

Dr. Garrido-Castro’s study will collect tumor samples and blood samples for the purposes of planned correlative analyses to try to better understand the mechanisms that drive response and resistance to these agents.

Dr. Giordano commented that Dr. Garrido-Castro’s study was likely to result in a much better understanding of ADCs and how to use them strategically.

At Dana-Farber, “we collect a lot of samples of patients receiving ADCs. And we are trying to do all kinds of work on circulating tumor DNA, immunohistochemistry expression, and protein expression,” he said. “We are trying to figure out how ADCs really work, and why they stop working.”

Dr. Giordano and colleagues’ study was funded by Astellas Pharma and by Seagen, which was bought by Pfizer in 2023. Dr. Giordano disclosed receiving consulting fees from Pfizer, and several of his coauthors reported relationships with this and other companies. Two were Astellas employees.

Dr. Garrido-Castro and colleagues’ study was funded by Merck and Gilead Sciences. Dr. Garrido-Castro disclosed receiving research support from Gilead Sciences, AstraZeneca, Daiichi Sankyo, Merck, Zenith Epigenetics, Bristol-Myers Squibb, Novartis, Biovica, Foundation Medicine, 4D Path, Precede Biosciences; scientific advisory board/consulting fees from AstraZeneca, Novartis, Daiichi Sankyo; speaker honoraria from AstraZeneca, Daiichi Sankyo; and other support from Roche/Genentech, Gilead Sciences, AstraZeneca, Daiichi Sankyo, Novartis, and Merck, while her coauthors reported similar relationships.

CHICAGO — The landscape of antibody-drug conjugates, or ADCs, continues to grow more crowded in metastatic breast cancer. Indications are expanding, new agents are emerging, combinations with other drug classes are being tested, and many patients with this disease are now receiving more than one ADC.

ADCs use antibodies to bind to the surface proteins of cancer cells to deliver a potent payload of cytotoxic chemotherapy. Three are approved for use in pretreated patients with metastatic breast cancer: sacituzumab govitecan, or SG, for patients with triple-negative disease; trastuzumab deruxtecan, or T-DXd, for patients with HER2-positive and HER2-low disease; and trastuzumab emtansine, or T-DM1, for patients with HER2-positive disease. A fourth agent, datopotamab deruxtecan, or Dato-DXd, is being assessed by the US Food and Drug Administration (FDA) for use in pretreated HR-positive, HER2-negative patients, and others, including sacituzumab tirumotecan, are being tested in clinical trials.At the annual meeting of the American Society of Clinical Oncology, T-DXd (Enhertu, AstraZeneca) showed better progression free survival than chemotherapy in people with HR-positive, HER 2-low metastatic breast cancers. These findings, from the DESTINY Breast-06 trial, were among the most talked-about at ASCO, and are likely to change clinical practice (J Clin Oncol. 2024;42[suppl 17; abstr LBA1000]).

But other ADC results presented at ASCO showed that there is still much to be worked out about the timing and sequencing of these agents, as well as their synergy with other drug classes, in metastatic breast cancer.
 

An ADC gets its first test, and falls short

Antonio Giordano, MD, PhD, of the Dana-Farber Cancer Institute in Boston, presented findings from an open-label phase 2 study of the ADC enfortumab vedotin (EV), an agent currently approved for use in advanced or metastatic urothelial cancer, at ASCO. This study included two cohorts of previously treated metastatic breast cancer patients: one with triple-negative disease (n = 42) and the other with HR-positive HER2-negative (n = 45).

Dr. Giordano and his colleagues’ study is the first to look at this ADC in breast cancer. EV’s antibody targets the cell adhesion molecule Nectin-4.

The researchers found that though EV demonstrated anti-tumor activity in both cohorts — with 19% of the triple-negative patients and 15.6% of the HR-positive/HER2-negative patients responding — the results did not meet the prespecified response thresholds for either cohort. (J Clin Oncol. 2024;42[suppl 16; abstr 1005]).

In an interview, Dr. Giordano said that studies in urothelial cancer had shown better response to EV associated with more expression of Nectin-4, but this study did not see such clear associations between expression and response. While there is no question that Nectin-4 is highly expressed in breast cancer and therefore a viable target, he said, “it may need to be looked at a little more deeply.”

It could also be the case, Dr. Giordano said, that the effect of EV’s payload may have been less robust in participants who had been previously treated with taxane chemotherapy, as nearly all patients in the two cohorts were.

“Taxanes are microtubule disruptors. And with this drug we had a payload with pretty much the same mechanism of action,” Dr. Giordano said. Ideally, he said, he would like to test the agent in a first-line setting, possibly in combination with an immunotherapy agent.

The timing of ADCs is as important as their targets and their payloads — and something that investigators are still struggling to figure out, he said.

A third of the patients in the triple-negative cohort of his study had been previously treated with SG, and a handful of individuals with T-Dxd, he noted.

“We’re in the middle of an ADC revolution,” he said. “It’s really key to figure out the best sequencing for a patient and if it’s actually worth it to do it. Very often we see patients respond best to the first ADC. But sometimes we see patients that do not respond to the first ADC and then they respond to the second one. It’s not very frequent, but it happens.”
 

Hint of Benefit from Adding Immunotherapy to SG

In a separate presentation at ASCO, Ana C. Garrido-Castro, MD, also of the Dana-Farber Cancer Institute, presented results from the SACI-IO HR+ trial, a randomized phase 2 study of SG (Trodelvy, Gilead) with and without pembrolizumab (Keytruda, Merck) in 104 patients with metastatic HR-positive/HER2-negative breast cancer who received prior endocrine therapy and up to one chemotherapy regimen for advanced disease. SACI-IO HR+ is the first randomized trial to report the efficacy of a topoisomerase I-inhibitor ADC with an immune checkpoint inhibitor for the treatment of breast cancer.

The addition of the immune checkpoint inhibitor did not result in a significant improvement in median progression-free survival in the overall population, Dr. Garrido-Castro reported. Median PFS was 8.1 vs 6.2 months with the combination of SG plus pembrolizumab or sacituzumab govitecan alone, respectively. At a median follow-up of 12.5 months, there was also no significant difference seen in median overall survival (OS): 18.5 vs 18.0 months.

About 40% of participants were found to have PD-L1-positive tumors and, among this subgroup, there was a 4.4-month increase in median PFS and 6.0-month increase in median OS with the addition of pembrolizumab to SG, although this did not reach statistical significance. (J Clin Oncol. 2024;42[suppl 17; abstr LBA1004]).

“While the study did not demonstrate a statistically significant benefit with the addition of the immune checkpoint inhibitor to the ADC, there is an interesting signal for potential synergistic activity between the two agents, particularly in those patients with PD-L1 positive tumors,” Dr. Garrido-Castro said in an interview. She noted that the sample sizes for the PD-L1 subgroup were relatively small, and overall survival data are not yet mature.

A separate phase 3 study is looking at the experimental ADC called sacituzumab tirumotecan with and without pembrolizumab compared with chemotherapy in patients with metastatic HR-positive, HER2-negative breast cancer who have received prior endocrine therapy and no prior chemotherapy for metastatic disease, she said.

Similar to SG, sacituzumab tirumotecan is a TROP2-directed ADC with a topoisomerase I-inhibitor payload. With an estimated enrollment of 1,200 patients, this trial may help shed light on whether adding the immune checkpoint inhibitor to the topoisomerase I-inhibitor TROP2-directed ADC improves outcomes in the subgroup of patients with PD-L1 positive tumors, Dr. Garrido-Castro said.
 

Unlocking the Order and Timing of ADCs

Dr. Garrido-Castro is also leading a study that will evaluate the sequential use of ADCs in metastatic breast cancer. That trial, to be called TRADE-DXd, will enroll patients with HER2-low metastatic breast cancer who have received up to one prior line of chemotherapy and no previous topoisomerase I-inhibitors. Participants will receive either T-DXd or Dato-DXd as the first ADC, and then switch to the other ADC (Dato-DXd or T-DXd, respectively) at the time of progression, thus switching the target of the ADC from HER2 to TROP2 or vice versa.

“In real-world practice now, there are patients who receive sequential ADCs, because they are candidates for both,” Dr. Garrido-Castro explained. However, more robust data are needed to refine the selection of the initial antibody drug conjugate and to determine who is more likely to benefit from a second — or maybe even third — ADC.

“One potential mechanism of resistance to antibody drug conjugates is the downregulation of the target of the antibody drug conjugate,” Dr. Garrido-Castro said. “Thus, an important question is, if you modify the target of the ADC, is it possible to overcome that mechanism of resistance?” Another possible mechanism of resistance is to the chemotherapy payload of the ADCs, she said.

Dr. Garrido-Castro’s study will collect tumor samples and blood samples for the purposes of planned correlative analyses to try to better understand the mechanisms that drive response and resistance to these agents.

Dr. Giordano commented that Dr. Garrido-Castro’s study was likely to result in a much better understanding of ADCs and how to use them strategically.

At Dana-Farber, “we collect a lot of samples of patients receiving ADCs. And we are trying to do all kinds of work on circulating tumor DNA, immunohistochemistry expression, and protein expression,” he said. “We are trying to figure out how ADCs really work, and why they stop working.”

Dr. Giordano and colleagues’ study was funded by Astellas Pharma and by Seagen, which was bought by Pfizer in 2023. Dr. Giordano disclosed receiving consulting fees from Pfizer, and several of his coauthors reported relationships with this and other companies. Two were Astellas employees.

Dr. Garrido-Castro and colleagues’ study was funded by Merck and Gilead Sciences. Dr. Garrido-Castro disclosed receiving research support from Gilead Sciences, AstraZeneca, Daiichi Sankyo, Merck, Zenith Epigenetics, Bristol-Myers Squibb, Novartis, Biovica, Foundation Medicine, 4D Path, Precede Biosciences; scientific advisory board/consulting fees from AstraZeneca, Novartis, Daiichi Sankyo; speaker honoraria from AstraZeneca, Daiichi Sankyo; and other support from Roche/Genentech, Gilead Sciences, AstraZeneca, Daiichi Sankyo, Novartis, and Merck, while her coauthors reported similar relationships.

Nonphysician operators (NPOs) using laser and energy-based devices are accounting for an increasing share of malpractice lawsuits in dermatology, and when they use these devices in a dermatologic practice or a dermatologist-owned medical spa, the dermatologist can be on the hook for liability. Dermatologists can protect themselves by understanding malpractice trends and taking preventive steps, such as making sure NPOs have appropriate training and using a rigorous informed consent process, according to a dermatology resident and a dermatologist who have researched recent trends in dermatology lawsuits.

“It’s really important that physicians recognize their responsibility when delegating procedures to nonphysician operators and the physician’s role in supervision of these procedures,” Scott Stratman, MD, MPH, a dermatology resident at the Icahn School of Medicine at Mount Sinai, New York City, told this news organization. He led a  study recently published in the Journal of the American Academy of Dermatology, which found that the majority (52%) of malpractice cases for cutaneous energy-based device procedures in the LexisNexis database from 1985 to September 2023 involved NPOs. The study did not break the data down between different types of NPOs.

Dr. Stratman

Trends in Dermatology Malpractice

This follows a similar trend reported in a 2014 study led by Mathew M. Avram, MD, JD, director of the MGH Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston. The study analyzed liability claims related to cutaneous laser surgery performed by nonphysicians from January 1999 to December 2012.

“With nonphysician litigation data, we saw trend lines beginning in 2008 where the proportion of cases began to increase,” Dr. Avram said at the American Society for Laser Medicine and Surgery (ASLMS) meeting on April 12, 2024. “Over a period of 2008-2012, it went from 36% of cases to about 78%,” he said.

About a quarter (23.4%) of those were in medical offices; 76.6% were in nontraditional settings such as medical spas, he added. The proportion of NPOs was similar in a 2022 study that looked at causes of litigation in cutaneous laser surgery from 2012 to 2020, Dr. Avram said. Again, neither study broke down cases involving NPOs by specific type, but the 2014 study reported that 64% of cases by NPOs occurred outside of a traditional medical setting.

“So it seems that the location and potentially the supervision are issues that are important to patient safety,” Dr. Avram said at the meeting. While state laws regarding laser delegation vary widely, “depending on where you practice, it’s incumbent upon you to know that.”

Dr. Avram and colleagues were also the authors of a study published in June in Dermatologic Surgery that looked at the reasons behind ligations involving dermatologists in a retrospective analysis of 48 state and federal cases between 2011 and 2022. The majority of cases — 54.2% — were for unexpected harm, followed by wrong or delayed diagnoses, which accounted for a third of litigations.

Dr. Stratman’s study found that laser hair removal was the most common procedure for malpractice claims in dermatology among cutaneous energy-based device procedures. Complications from energy-based devices included burns, scarring, and pigmentation changes.

The growth of malpractice suits involving NPOs could be because NPOs are performing a greater proportion of dermatologic procedures, “particularly those practicing without direct supervision, such as in the context of a medical spa,” Dr. Stratman said in the interview. “Again, this highlights a physician’s responsibility in delegating these kinds of procedures to NPOs.”
 

Training Is a Must — But Not Standardized

Comprehensive training for physicians, staff, NPOs, and physicians “is all necessary and paramount in order to diminish adverse outcomes and legal risk, and then, of course, all these practitioners, be it staff or [NPOs], and, of course, physicians, are all held to the same standard of care,” Dr. Stratman said.

However, he added, “There is really no standardized training to operate these devices. That being said, it’s really important to know that both providers and facility owners have a significant obligation to their patients to make sure that their staff in their centers are appropriately trained.”

Training not only involves protocols and procedures but also how to handle patient interactions, Dr. Stratman said.

The legal concept of respondeat superior applies when nonphysicians participate in a patient’s care, Dr. Avram said at the ASLMS meeting. The physician is held liable for a nonphysician’s “negligence provided he or she is an employee receiving a salary [and] benefits and is performing within the scope of his or her duty,” regardless of whether the physician saw the patient or not at that visit, he said. Again, supervision of nonphysician laser procedures varies from state to state, he added.

“So the take-home point is to provide excellent training and appropriate supervision, and if you’re the owner of that practice, you are liable in the event of negligence even though you never were part of the treatment,” Dr. Avram said.

Ins and Outs of Informed Consent

When a patient outcome is less than desirable, or at least less than what the patient expected, a transparent and thorough informed consent process can protect the practice and physician, Dr. Avram said at the meeting.

“Malpractice and consent have nothing to do with each other,” he said. “Consent is getting permission to do a procedure. It’s needed actually for any medical intervention that you perform. What you need to do is to provide information to enable the patient or guardian or to choose knowledgeably among reasonable medical alternatives. This places the patient in control of the course of their medical treatment.”

The information conveyed to the patient should include the diagnosis, the medical causes, the nature and purpose of the treatment, and the risks and alternatives of procedure, “particularly if they’re high risk,” Dr. Avram said.

“Failure to obtain informed consent constitutes a civil battery, and the physician is liable for civil damages,” he said. “The patient need only show that he or she was not informed of the medical nature of the medical touching; physical injury is not necessary.”

A battery could occur if a procedure extends beyond the scope or area of treatment the patient agreed to — for example, extending a liposuction to an area that wasn’t originally targeted, or extending a laser procedure to an area of the body as a presumed favor to the patient. “It does not require a standard of care or an expert witness,” Dr. Avram said. “One only needs to show nonconsensual touching.”

Informed consents should include plain language, he said. “The whole idea is the patient understands what the risks and benefits are,” Dr. Avram said. “You don’t need to use medical jargon.” As an example, he suggested using the term “blisters” instead of “bullae.” If the treatment involves an off-label procedure, include that too, he said.

He also advised avoiding blanket authorizations. “Courts disfavor them,” he noted. “They need more specificity. So those are not valid.”

Dr. Stratman added that providers should think about the setting in which they obtain informed consent. “It’s really important that providers are consenting their patients in private and quiet places, free from distractions, that they accommodate patients who might have disabilities or limitations in English proficiency, using a teach-back method to help patients understand or demonstrate their understanding of the procedure in order to gauge comprehension,” he said.

Both Dr. Avram and Dr. Stratman pointed out that another strategy to prevent malpractice is to build trusting patient-provider relationships. “The patient-provider relationship is paramount not only to the success of the procedure but to the clinical visit as a whole,” Dr. Stratman said.

That’s a two-way street, he added. Patients should be able to trust that their provider provides them with the best treatment based on their own history, and providers should also be able to trust that patients are providing them with an accurate history, asking relevant questions, or expressing any level of apprehension about the procedure or visit. “The patient-provider relationship is everything,” Dr. Stratman said.

Dr. Stratman and Dr. Avram had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Nonphysician operators (NPOs) using laser and energy-based devices are accounting for an increasing share of malpractice lawsuits in dermatology, and when they use these devices in a dermatologic practice or a dermatologist-owned medical spa, the dermatologist can be on the hook for liability. Dermatologists can protect themselves by understanding malpractice trends and taking preventive steps, such as making sure NPOs have appropriate training and using a rigorous informed consent process, according to a dermatology resident and a dermatologist who have researched recent trends in dermatology lawsuits.

“It’s really important that physicians recognize their responsibility when delegating procedures to nonphysician operators and the physician’s role in supervision of these procedures,” Scott Stratman, MD, MPH, a dermatology resident at the Icahn School of Medicine at Mount Sinai, New York City, told this news organization. He led a  study recently published in the Journal of the American Academy of Dermatology, which found that the majority (52%) of malpractice cases for cutaneous energy-based device procedures in the LexisNexis database from 1985 to September 2023 involved NPOs. The study did not break the data down between different types of NPOs.

Dr. Stratman

Trends in Dermatology Malpractice

This follows a similar trend reported in a 2014 study led by Mathew M. Avram, MD, JD, director of the MGH Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston. The study analyzed liability claims related to cutaneous laser surgery performed by nonphysicians from January 1999 to December 2012.

“With nonphysician litigation data, we saw trend lines beginning in 2008 where the proportion of cases began to increase,” Dr. Avram said at the American Society for Laser Medicine and Surgery (ASLMS) meeting on April 12, 2024. “Over a period of 2008-2012, it went from 36% of cases to about 78%,” he said.

About a quarter (23.4%) of those were in medical offices; 76.6% were in nontraditional settings such as medical spas, he added. The proportion of NPOs was similar in a 2022 study that looked at causes of litigation in cutaneous laser surgery from 2012 to 2020, Dr. Avram said. Again, neither study broke down cases involving NPOs by specific type, but the 2014 study reported that 64% of cases by NPOs occurred outside of a traditional medical setting.

“So it seems that the location and potentially the supervision are issues that are important to patient safety,” Dr. Avram said at the meeting. While state laws regarding laser delegation vary widely, “depending on where you practice, it’s incumbent upon you to know that.”

Dr. Avram and colleagues were also the authors of a study published in June in Dermatologic Surgery that looked at the reasons behind ligations involving dermatologists in a retrospective analysis of 48 state and federal cases between 2011 and 2022. The majority of cases — 54.2% — were for unexpected harm, followed by wrong or delayed diagnoses, which accounted for a third of litigations.

Dr. Stratman’s study found that laser hair removal was the most common procedure for malpractice claims in dermatology among cutaneous energy-based device procedures. Complications from energy-based devices included burns, scarring, and pigmentation changes.

The growth of malpractice suits involving NPOs could be because NPOs are performing a greater proportion of dermatologic procedures, “particularly those practicing without direct supervision, such as in the context of a medical spa,” Dr. Stratman said in the interview. “Again, this highlights a physician’s responsibility in delegating these kinds of procedures to NPOs.”
 

Training Is a Must — But Not Standardized

Comprehensive training for physicians, staff, NPOs, and physicians “is all necessary and paramount in order to diminish adverse outcomes and legal risk, and then, of course, all these practitioners, be it staff or [NPOs], and, of course, physicians, are all held to the same standard of care,” Dr. Stratman said.

However, he added, “There is really no standardized training to operate these devices. That being said, it’s really important to know that both providers and facility owners have a significant obligation to their patients to make sure that their staff in their centers are appropriately trained.”

Training not only involves protocols and procedures but also how to handle patient interactions, Dr. Stratman said.

The legal concept of respondeat superior applies when nonphysicians participate in a patient’s care, Dr. Avram said at the ASLMS meeting. The physician is held liable for a nonphysician’s “negligence provided he or she is an employee receiving a salary [and] benefits and is performing within the scope of his or her duty,” regardless of whether the physician saw the patient or not at that visit, he said. Again, supervision of nonphysician laser procedures varies from state to state, he added.

“So the take-home point is to provide excellent training and appropriate supervision, and if you’re the owner of that practice, you are liable in the event of negligence even though you never were part of the treatment,” Dr. Avram said.

Ins and Outs of Informed Consent

When a patient outcome is less than desirable, or at least less than what the patient expected, a transparent and thorough informed consent process can protect the practice and physician, Dr. Avram said at the meeting.

“Malpractice and consent have nothing to do with each other,” he said. “Consent is getting permission to do a procedure. It’s needed actually for any medical intervention that you perform. What you need to do is to provide information to enable the patient or guardian or to choose knowledgeably among reasonable medical alternatives. This places the patient in control of the course of their medical treatment.”

The information conveyed to the patient should include the diagnosis, the medical causes, the nature and purpose of the treatment, and the risks and alternatives of procedure, “particularly if they’re high risk,” Dr. Avram said.

“Failure to obtain informed consent constitutes a civil battery, and the physician is liable for civil damages,” he said. “The patient need only show that he or she was not informed of the medical nature of the medical touching; physical injury is not necessary.”

A battery could occur if a procedure extends beyond the scope or area of treatment the patient agreed to — for example, extending a liposuction to an area that wasn’t originally targeted, or extending a laser procedure to an area of the body as a presumed favor to the patient. “It does not require a standard of care or an expert witness,” Dr. Avram said. “One only needs to show nonconsensual touching.”

Informed consents should include plain language, he said. “The whole idea is the patient understands what the risks and benefits are,” Dr. Avram said. “You don’t need to use medical jargon.” As an example, he suggested using the term “blisters” instead of “bullae.” If the treatment involves an off-label procedure, include that too, he said.

He also advised avoiding blanket authorizations. “Courts disfavor them,” he noted. “They need more specificity. So those are not valid.”

Dr. Stratman added that providers should think about the setting in which they obtain informed consent. “It’s really important that providers are consenting their patients in private and quiet places, free from distractions, that they accommodate patients who might have disabilities or limitations in English proficiency, using a teach-back method to help patients understand or demonstrate their understanding of the procedure in order to gauge comprehension,” he said.

Both Dr. Avram and Dr. Stratman pointed out that another strategy to prevent malpractice is to build trusting patient-provider relationships. “The patient-provider relationship is paramount not only to the success of the procedure but to the clinical visit as a whole,” Dr. Stratman said.

That’s a two-way street, he added. Patients should be able to trust that their provider provides them with the best treatment based on their own history, and providers should also be able to trust that patients are providing them with an accurate history, asking relevant questions, or expressing any level of apprehension about the procedure or visit. “The patient-provider relationship is everything,” Dr. Stratman said.

Dr. Stratman and Dr. Avram had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Nonphysician operators (NPOs) using laser and energy-based devices are accounting for an increasing share of malpractice lawsuits in dermatology, and when they use these devices in a dermatologic practice or a dermatologist-owned medical spa, the dermatologist can be on the hook for liability. Dermatologists can protect themselves by understanding malpractice trends and taking preventive steps, such as making sure NPOs have appropriate training and using a rigorous informed consent process, according to a dermatology resident and a dermatologist who have researched recent trends in dermatology lawsuits.

“It’s really important that physicians recognize their responsibility when delegating procedures to nonphysician operators and the physician’s role in supervision of these procedures,” Scott Stratman, MD, MPH, a dermatology resident at the Icahn School of Medicine at Mount Sinai, New York City, told this news organization. He led a  study recently published in the Journal of the American Academy of Dermatology, which found that the majority (52%) of malpractice cases for cutaneous energy-based device procedures in the LexisNexis database from 1985 to September 2023 involved NPOs. The study did not break the data down between different types of NPOs.

Dr. Stratman

Trends in Dermatology Malpractice

This follows a similar trend reported in a 2014 study led by Mathew M. Avram, MD, JD, director of the MGH Dermatology Laser and Cosmetic Center at Massachusetts General Hospital, Boston. The study analyzed liability claims related to cutaneous laser surgery performed by nonphysicians from January 1999 to December 2012.

“With nonphysician litigation data, we saw trend lines beginning in 2008 where the proportion of cases began to increase,” Dr. Avram said at the American Society for Laser Medicine and Surgery (ASLMS) meeting on April 12, 2024. “Over a period of 2008-2012, it went from 36% of cases to about 78%,” he said.

About a quarter (23.4%) of those were in medical offices; 76.6% were in nontraditional settings such as medical spas, he added. The proportion of NPOs was similar in a 2022 study that looked at causes of litigation in cutaneous laser surgery from 2012 to 2020, Dr. Avram said. Again, neither study broke down cases involving NPOs by specific type, but the 2014 study reported that 64% of cases by NPOs occurred outside of a traditional medical setting.

“So it seems that the location and potentially the supervision are issues that are important to patient safety,” Dr. Avram said at the meeting. While state laws regarding laser delegation vary widely, “depending on where you practice, it’s incumbent upon you to know that.”

Dr. Avram and colleagues were also the authors of a study published in June in Dermatologic Surgery that looked at the reasons behind ligations involving dermatologists in a retrospective analysis of 48 state and federal cases between 2011 and 2022. The majority of cases — 54.2% — were for unexpected harm, followed by wrong or delayed diagnoses, which accounted for a third of litigations.

Dr. Stratman’s study found that laser hair removal was the most common procedure for malpractice claims in dermatology among cutaneous energy-based device procedures. Complications from energy-based devices included burns, scarring, and pigmentation changes.

The growth of malpractice suits involving NPOs could be because NPOs are performing a greater proportion of dermatologic procedures, “particularly those practicing without direct supervision, such as in the context of a medical spa,” Dr. Stratman said in the interview. “Again, this highlights a physician’s responsibility in delegating these kinds of procedures to NPOs.”
 

Training Is a Must — But Not Standardized

Comprehensive training for physicians, staff, NPOs, and physicians “is all necessary and paramount in order to diminish adverse outcomes and legal risk, and then, of course, all these practitioners, be it staff or [NPOs], and, of course, physicians, are all held to the same standard of care,” Dr. Stratman said.

However, he added, “There is really no standardized training to operate these devices. That being said, it’s really important to know that both providers and facility owners have a significant obligation to their patients to make sure that their staff in their centers are appropriately trained.”

Training not only involves protocols and procedures but also how to handle patient interactions, Dr. Stratman said.

The legal concept of respondeat superior applies when nonphysicians participate in a patient’s care, Dr. Avram said at the ASLMS meeting. The physician is held liable for a nonphysician’s “negligence provided he or she is an employee receiving a salary [and] benefits and is performing within the scope of his or her duty,” regardless of whether the physician saw the patient or not at that visit, he said. Again, supervision of nonphysician laser procedures varies from state to state, he added.

“So the take-home point is to provide excellent training and appropriate supervision, and if you’re the owner of that practice, you are liable in the event of negligence even though you never were part of the treatment,” Dr. Avram said.

Ins and Outs of Informed Consent

When a patient outcome is less than desirable, or at least less than what the patient expected, a transparent and thorough informed consent process can protect the practice and physician, Dr. Avram said at the meeting.

“Malpractice and consent have nothing to do with each other,” he said. “Consent is getting permission to do a procedure. It’s needed actually for any medical intervention that you perform. What you need to do is to provide information to enable the patient or guardian or to choose knowledgeably among reasonable medical alternatives. This places the patient in control of the course of their medical treatment.”

The information conveyed to the patient should include the diagnosis, the medical causes, the nature and purpose of the treatment, and the risks and alternatives of procedure, “particularly if they’re high risk,” Dr. Avram said.

“Failure to obtain informed consent constitutes a civil battery, and the physician is liable for civil damages,” he said. “The patient need only show that he or she was not informed of the medical nature of the medical touching; physical injury is not necessary.”

A battery could occur if a procedure extends beyond the scope or area of treatment the patient agreed to — for example, extending a liposuction to an area that wasn’t originally targeted, or extending a laser procedure to an area of the body as a presumed favor to the patient. “It does not require a standard of care or an expert witness,” Dr. Avram said. “One only needs to show nonconsensual touching.”

Informed consents should include plain language, he said. “The whole idea is the patient understands what the risks and benefits are,” Dr. Avram said. “You don’t need to use medical jargon.” As an example, he suggested using the term “blisters” instead of “bullae.” If the treatment involves an off-label procedure, include that too, he said.

He also advised avoiding blanket authorizations. “Courts disfavor them,” he noted. “They need more specificity. So those are not valid.”

Dr. Stratman added that providers should think about the setting in which they obtain informed consent. “It’s really important that providers are consenting their patients in private and quiet places, free from distractions, that they accommodate patients who might have disabilities or limitations in English proficiency, using a teach-back method to help patients understand or demonstrate their understanding of the procedure in order to gauge comprehension,” he said.

Both Dr. Avram and Dr. Stratman pointed out that another strategy to prevent malpractice is to build trusting patient-provider relationships. “The patient-provider relationship is paramount not only to the success of the procedure but to the clinical visit as a whole,” Dr. Stratman said.

That’s a two-way street, he added. Patients should be able to trust that their provider provides them with the best treatment based on their own history, and providers should also be able to trust that patients are providing them with an accurate history, asking relevant questions, or expressing any level of apprehension about the procedure or visit. “The patient-provider relationship is everything,” Dr. Stratman said.

Dr. Stratman and Dr. Avram had no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

An elderly gentleman was truly suffering, so his doctor decided to try something new.

“He’d had a number of cumulative side effects after almost two years of IV chemotherapy for his metastatic colon cancer,” said Anuj Patel, MD, a senior physician at Dana-Farber Cancer Institute in Boston, recalling his patient. “When we switched him to combination treatment with trifluridine/tipiracil and bevacizumab, he constantly remarked on how well he now felt. He described no side effects from this new regimen.”

Nearly a year after the US Food and Drug Administration (FDA) approved trifluridine/tipiracil combined with bevacizumab for refractory mCRC, the tremendous value of its results in practice are clear.

Trifluridine/tipiracil (Lonsurf) had been used to treat advanced gastric cancer, while bevacizumab had been therapeutic for a wider range of diseases, including cervical, brain, liver, kidney, gynecological and lung cancers. Used together for treating refractory mCRC, well-known initial findings about their effectiveness have been proven true over time.

“Patients taking both drugs can experience, on average, a life extension of three months,” said Richard M. Goldberg, MD, professor emeritus of the West Virginia University Cancer Institute and director of Fight Colorectal Cancer.
 

The History of the Combined Therapy’s Approval

The FDA originally approved trifluridine/tipiracil in September 2015 for use in patients with metastatic colorectal cancer. Patients eligible to take it had to have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and—if RAS wild-type—an anti-epidermal growth factor receptor (EGFR) therapy, according to data published by the National Center for Biotechnology Information. The FDA’s August 2023 approval of the trifluridine/tipiracil and bevacizumab combination regimen is for patients meeting the same eligibility requirements.

Another drug, regorafenib, had already been approved by the FDA in September 2012 to treat mCRC. The drug has a wide range of potential side effects, however, including complications relating to the limbs.

“One of my patients tried regorafenib as his initial third- line treatment,” Dr. Goldberg said. “I checked in on him at his farm, and he was sitting in the barn near his tractor.

He had such severe hand-foot syndrome that he could barely walk.”

Trifluridine/tipiracil alone proved to be very helpful in this case. “We switched him to it, and he tolerated it well,” Dr. Goldberg continued. “He got his fields plowed and was on it for months before he passed away. We both felt it kept him going longer.”

A new research review confirms the regimen’s success, determining that trifluridine/tipiracil plus bevacizumab was associated with improved outcomes compared to therapy solely with trifluridine/tipiracil.
 

A True Practice Changer

Now that the regimen has been on the market for more than half a year, there are longer-term data available.

Patients on average live within the same timeframe as the patients in the SUNLIGHT study, and many feel physically better on the therapy. “The combination has very quickly shifted the standard of care,” Dr. Goldberg said.

The regimen can also provide significant psychological benefits to patients.

“As patients can maintain good performance status for longer with the combination, it increases the perception of quality of life,” said Jacobo Hincapie-Echeverri, MD, a GI and geriatric oncologist at Orlando Health Cancer Institute in Orlando, Florida.

The regimen is unique too, in that it can help doctors plan additional treatment strategies.

“This current approval, for the combination of trifluridine/tipiracil and bevacizumab, is practice-changing in that it helps clarify the sequence for later treatments for patients with mCRC,” said Dr. Patel, who is also clinical director of the Center for Esophageal and Gastric Cancer and assistant professor of medicine at Harvard Medical School, Boston. “Previously, it had been difficult to decide between trifluridine/tipiracil and regorafenib in this setting.”

The fact that the regimen has been shown to give time and improved quality of life to patients in ways regorafenib does not is clarifying. “Now, with the improved outcomes seen, I do think that trifluridine/tipiracil plus bevacizumab is the better option for most mCRC patients after IV chemotherapies,” Dr. Patel added.

When it comes to his specific experience with prescribing the regimen for his patients, Dr. Patel reported that it’s easier on his patients than other therapies.

“I find that it is generally well tolerated,” he elaborated. “As an oral agent, it is also usually somewhat easier to take (than other delivery methods of medication). These factors are critical for patients who have likely already had at least 2 or 3 prior lines of chemotherapy. I have had many patients with mCRC who, after disease progression on prior IV chemotherapy regimens, have had periods of meaningful disease control – often with fewer and manageable side effects.”

Dr. Goldberg mentioned another benefit.

“The nice thing about the combination of trifluridine/tipiracil and bevacizumab is that in terms of toxicity, there’s very little difference compared to the toxicity of trifluridine/tipiracil used alone.”
 

Are There Downsides to the Regimen?

The pros are obvious, but the regimen has some cons as well. Medically, patients should have a platelet count over 75,000/mm³ and absolute neutrophil count (ANC) over 1,500/mm³ prior to the start of each cycle, and their liver and renal function should be monitored.

Patients with metastatic colorectal cancer must be also carefully monitored for hematologic adverse events (AEs) , including chemotherapy-associated neutropenia. Biweekly treatments may reduce the risk of AEs as a whole, however, according to research.

The regimen is also expensive – an approximate cost of $8,191 for a 28-day supply. According to a new study, patients managing both AE expenses along with the cost of trifluridine/tipiracil-bevacizumab face a monthly bill of about $17,179.

Some very good news, though: 100% of Medicare drug plans cover trifluridine/tipiracil, with an average copay of $57-$292. Bevacizumab is also covered by Medicare, with a copay as low as $0-$25.

Private insurers do cover the drugs, depending on a patient’s specific plan. However, if a patient’s claim is denied, financial assistance for trifluridine/tipiracil through the drug’s manufacturers may be available for some patients, reducing prescriptions to a zero cost in some cases. Bevacizumab can be made available to patients who may not have health insurance at all, too. Patients can use a financial assistance tool through the drug’s manufacturer to receive up to $25,000 in yearly copay assistance.
 

What Does the Latest Research on the Regimen Indicate?

In May 2024, two abstracts were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) that explored expanded possible use of trifluridine/tipiracil plus bevacizumab as a treatment for metastatic colorectal cancer.

The first abstract studied trifluridine/tipiracil plus bevacizumab as upfront treatment for mCRC, adding capecitabine to the regimen.

“It’s a phase 1 study looking at dose findings for the three-drug combination, where the active drug is a chemotherapy agent classified as a fluoropyrimidine ... I would characterize this as a study combining two [fluoropyrimidines] with a single targeted therapy,” Dr. Goldberg said.

“Combining two fluoropyrimidines is an unusual approach, because they tend to have overlapping side effects, and the potential is there for either innate drug resistance to the class of drugs or that the combination of two agents that work by a similar mechanism of action could hasten the development of acquired drug resistance. There is apparently a signal that combining the two chemotherapy agents enhances each other’s activity in cell culture and animal models,” he added.

Ultimately, Dr. Goldberg said he thinks more evidence is needed to prove the regimen’s effectiveness.

“This is a very early study and really provides no information about its potential given that no response data was presented,” he added. “While this is an interesting idea, it is unclear if it will pan out until we see the data on the Phase II study in progress.”

The other abstract looked at the impact of colorectal liver metastases in patients with mCRC who in phase 3 of the SUNLIGHT trial received trifluridine/tipiracil with or without bevacizumab.

“There is not much that is novel here,” Dr. Goldberg said. “The retrospective analysis shows that trifluridine/tipiracil plus bevacizumab is better than trifluridine/tipiracil alone in the subset of patients with liver metastases, as it was shown to be in the entire patient population. While this is reassuring, it’s not unexpected, especially since the vast majority of people enrolled in the SUNLIGHT trial had liver metastases.”

The Bottom Line

In the future, the potential exists for trifluridine/tipiracil combined with bevacizumab to work in first-line and second-line patients.

“Seventy percent of colorectal cancer patients reach second line treatment right now, but only 30% reach third line treatment — either they become too sick to continue, or choose not to,” Dr. Goldberg said. “The hope is that using these drugs earlier can help more patients reach and prolong treatment.”

It’s also possible that the regimen can be applied in new ways.

“Further research combining trifluridine/tipiracil and bevacizumab with other targeted therapies could yield additional advances for refractory mCRC patients,” Dr. Hincapie-Echeverri said. “The survival benefit of this therapy reinforces the importance of continuing to develop new therapies to improve outcomes in the refractory mCRC setting.”

Dr. Patel’s patient felt lucky to simply live a longer life.

Because of the regimen, “his cancer remained stable for approximately 8 months. Upon its progression, he chose not to pursue any further chemotherapy. He instead expressed his gratitude at having been able to feel more like himself for nearly a year.”

Dr. Patel received research funding in 2017 from Taiho, which manufactures trifluridine/tipiracil. He receives no current funding from Taiho and has no additional conflicts of interest. Dr. Goldberg helped represent Taiho in a patent law dispute regarding Lonsurf for which he was paid, but he is no longer paid by the company. Dr. Hincapie-Echeverri is a speaker for Astellas Pharma, which does not manufacture trifluridine/tipiracil or bevacizumab, and he has no additional conflicts of interest.

An elderly gentleman was truly suffering, so his doctor decided to try something new.

“He’d had a number of cumulative side effects after almost two years of IV chemotherapy for his metastatic colon cancer,” said Anuj Patel, MD, a senior physician at Dana-Farber Cancer Institute in Boston, recalling his patient. “When we switched him to combination treatment with trifluridine/tipiracil and bevacizumab, he constantly remarked on how well he now felt. He described no side effects from this new regimen.”

Nearly a year after the US Food and Drug Administration (FDA) approved trifluridine/tipiracil combined with bevacizumab for refractory mCRC, the tremendous value of its results in practice are clear.

Trifluridine/tipiracil (Lonsurf) had been used to treat advanced gastric cancer, while bevacizumab had been therapeutic for a wider range of diseases, including cervical, brain, liver, kidney, gynecological and lung cancers. Used together for treating refractory mCRC, well-known initial findings about their effectiveness have been proven true over time.

“Patients taking both drugs can experience, on average, a life extension of three months,” said Richard M. Goldberg, MD, professor emeritus of the West Virginia University Cancer Institute and director of Fight Colorectal Cancer.
 

The History of the Combined Therapy’s Approval

The FDA originally approved trifluridine/tipiracil in September 2015 for use in patients with metastatic colorectal cancer. Patients eligible to take it had to have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and—if RAS wild-type—an anti-epidermal growth factor receptor (EGFR) therapy, according to data published by the National Center for Biotechnology Information. The FDA’s August 2023 approval of the trifluridine/tipiracil and bevacizumab combination regimen is for patients meeting the same eligibility requirements.

Another drug, regorafenib, had already been approved by the FDA in September 2012 to treat mCRC. The drug has a wide range of potential side effects, however, including complications relating to the limbs.

“One of my patients tried regorafenib as his initial third- line treatment,” Dr. Goldberg said. “I checked in on him at his farm, and he was sitting in the barn near his tractor.

He had such severe hand-foot syndrome that he could barely walk.”

Trifluridine/tipiracil alone proved to be very helpful in this case. “We switched him to it, and he tolerated it well,” Dr. Goldberg continued. “He got his fields plowed and was on it for months before he passed away. We both felt it kept him going longer.”

A new research review confirms the regimen’s success, determining that trifluridine/tipiracil plus bevacizumab was associated with improved outcomes compared to therapy solely with trifluridine/tipiracil.
 

A True Practice Changer

Now that the regimen has been on the market for more than half a year, there are longer-term data available.

Patients on average live within the same timeframe as the patients in the SUNLIGHT study, and many feel physically better on the therapy. “The combination has very quickly shifted the standard of care,” Dr. Goldberg said.

The regimen can also provide significant psychological benefits to patients.

“As patients can maintain good performance status for longer with the combination, it increases the perception of quality of life,” said Jacobo Hincapie-Echeverri, MD, a GI and geriatric oncologist at Orlando Health Cancer Institute in Orlando, Florida.

The regimen is unique too, in that it can help doctors plan additional treatment strategies.

“This current approval, for the combination of trifluridine/tipiracil and bevacizumab, is practice-changing in that it helps clarify the sequence for later treatments for patients with mCRC,” said Dr. Patel, who is also clinical director of the Center for Esophageal and Gastric Cancer and assistant professor of medicine at Harvard Medical School, Boston. “Previously, it had been difficult to decide between trifluridine/tipiracil and regorafenib in this setting.”

The fact that the regimen has been shown to give time and improved quality of life to patients in ways regorafenib does not is clarifying. “Now, with the improved outcomes seen, I do think that trifluridine/tipiracil plus bevacizumab is the better option for most mCRC patients after IV chemotherapies,” Dr. Patel added.

When it comes to his specific experience with prescribing the regimen for his patients, Dr. Patel reported that it’s easier on his patients than other therapies.

“I find that it is generally well tolerated,” he elaborated. “As an oral agent, it is also usually somewhat easier to take (than other delivery methods of medication). These factors are critical for patients who have likely already had at least 2 or 3 prior lines of chemotherapy. I have had many patients with mCRC who, after disease progression on prior IV chemotherapy regimens, have had periods of meaningful disease control – often with fewer and manageable side effects.”

Dr. Goldberg mentioned another benefit.

“The nice thing about the combination of trifluridine/tipiracil and bevacizumab is that in terms of toxicity, there’s very little difference compared to the toxicity of trifluridine/tipiracil used alone.”
 

Are There Downsides to the Regimen?

The pros are obvious, but the regimen has some cons as well. Medically, patients should have a platelet count over 75,000/mm³ and absolute neutrophil count (ANC) over 1,500/mm³ prior to the start of each cycle, and their liver and renal function should be monitored.

Patients with metastatic colorectal cancer must be also carefully monitored for hematologic adverse events (AEs) , including chemotherapy-associated neutropenia. Biweekly treatments may reduce the risk of AEs as a whole, however, according to research.

The regimen is also expensive – an approximate cost of $8,191 for a 28-day supply. According to a new study, patients managing both AE expenses along with the cost of trifluridine/tipiracil-bevacizumab face a monthly bill of about $17,179.

Some very good news, though: 100% of Medicare drug plans cover trifluridine/tipiracil, with an average copay of $57-$292. Bevacizumab is also covered by Medicare, with a copay as low as $0-$25.

Private insurers do cover the drugs, depending on a patient’s specific plan. However, if a patient’s claim is denied, financial assistance for trifluridine/tipiracil through the drug’s manufacturers may be available for some patients, reducing prescriptions to a zero cost in some cases. Bevacizumab can be made available to patients who may not have health insurance at all, too. Patients can use a financial assistance tool through the drug’s manufacturer to receive up to $25,000 in yearly copay assistance.
 

What Does the Latest Research on the Regimen Indicate?

In May 2024, two abstracts were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) that explored expanded possible use of trifluridine/tipiracil plus bevacizumab as a treatment for metastatic colorectal cancer.

The first abstract studied trifluridine/tipiracil plus bevacizumab as upfront treatment for mCRC, adding capecitabine to the regimen.

“It’s a phase 1 study looking at dose findings for the three-drug combination, where the active drug is a chemotherapy agent classified as a fluoropyrimidine ... I would characterize this as a study combining two [fluoropyrimidines] with a single targeted therapy,” Dr. Goldberg said.

“Combining two fluoropyrimidines is an unusual approach, because they tend to have overlapping side effects, and the potential is there for either innate drug resistance to the class of drugs or that the combination of two agents that work by a similar mechanism of action could hasten the development of acquired drug resistance. There is apparently a signal that combining the two chemotherapy agents enhances each other’s activity in cell culture and animal models,” he added.

Ultimately, Dr. Goldberg said he thinks more evidence is needed to prove the regimen’s effectiveness.

“This is a very early study and really provides no information about its potential given that no response data was presented,” he added. “While this is an interesting idea, it is unclear if it will pan out until we see the data on the Phase II study in progress.”

The other abstract looked at the impact of colorectal liver metastases in patients with mCRC who in phase 3 of the SUNLIGHT trial received trifluridine/tipiracil with or without bevacizumab.

“There is not much that is novel here,” Dr. Goldberg said. “The retrospective analysis shows that trifluridine/tipiracil plus bevacizumab is better than trifluridine/tipiracil alone in the subset of patients with liver metastases, as it was shown to be in the entire patient population. While this is reassuring, it’s not unexpected, especially since the vast majority of people enrolled in the SUNLIGHT trial had liver metastases.”

The Bottom Line

In the future, the potential exists for trifluridine/tipiracil combined with bevacizumab to work in first-line and second-line patients.

“Seventy percent of colorectal cancer patients reach second line treatment right now, but only 30% reach third line treatment — either they become too sick to continue, or choose not to,” Dr. Goldberg said. “The hope is that using these drugs earlier can help more patients reach and prolong treatment.”

It’s also possible that the regimen can be applied in new ways.

“Further research combining trifluridine/tipiracil and bevacizumab with other targeted therapies could yield additional advances for refractory mCRC patients,” Dr. Hincapie-Echeverri said. “The survival benefit of this therapy reinforces the importance of continuing to develop new therapies to improve outcomes in the refractory mCRC setting.”

Dr. Patel’s patient felt lucky to simply live a longer life.

Because of the regimen, “his cancer remained stable for approximately 8 months. Upon its progression, he chose not to pursue any further chemotherapy. He instead expressed his gratitude at having been able to feel more like himself for nearly a year.”

Dr. Patel received research funding in 2017 from Taiho, which manufactures trifluridine/tipiracil. He receives no current funding from Taiho and has no additional conflicts of interest. Dr. Goldberg helped represent Taiho in a patent law dispute regarding Lonsurf for which he was paid, but he is no longer paid by the company. Dr. Hincapie-Echeverri is a speaker for Astellas Pharma, which does not manufacture trifluridine/tipiracil or bevacizumab, and he has no additional conflicts of interest.

An elderly gentleman was truly suffering, so his doctor decided to try something new.

“He’d had a number of cumulative side effects after almost two years of IV chemotherapy for his metastatic colon cancer,” said Anuj Patel, MD, a senior physician at Dana-Farber Cancer Institute in Boston, recalling his patient. “When we switched him to combination treatment with trifluridine/tipiracil and bevacizumab, he constantly remarked on how well he now felt. He described no side effects from this new regimen.”

Nearly a year after the US Food and Drug Administration (FDA) approved trifluridine/tipiracil combined with bevacizumab for refractory mCRC, the tremendous value of its results in practice are clear.

Trifluridine/tipiracil (Lonsurf) had been used to treat advanced gastric cancer, while bevacizumab had been therapeutic for a wider range of diseases, including cervical, brain, liver, kidney, gynecological and lung cancers. Used together for treating refractory mCRC, well-known initial findings about their effectiveness have been proven true over time.

“Patients taking both drugs can experience, on average, a life extension of three months,” said Richard M. Goldberg, MD, professor emeritus of the West Virginia University Cancer Institute and director of Fight Colorectal Cancer.
 

The History of the Combined Therapy’s Approval

The FDA originally approved trifluridine/tipiracil in September 2015 for use in patients with metastatic colorectal cancer. Patients eligible to take it had to have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and—if RAS wild-type—an anti-epidermal growth factor receptor (EGFR) therapy, according to data published by the National Center for Biotechnology Information. The FDA’s August 2023 approval of the trifluridine/tipiracil and bevacizumab combination regimen is for patients meeting the same eligibility requirements.

Another drug, regorafenib, had already been approved by the FDA in September 2012 to treat mCRC. The drug has a wide range of potential side effects, however, including complications relating to the limbs.

“One of my patients tried regorafenib as his initial third- line treatment,” Dr. Goldberg said. “I checked in on him at his farm, and he was sitting in the barn near his tractor.

He had such severe hand-foot syndrome that he could barely walk.”

Trifluridine/tipiracil alone proved to be very helpful in this case. “We switched him to it, and he tolerated it well,” Dr. Goldberg continued. “He got his fields plowed and was on it for months before he passed away. We both felt it kept him going longer.”

A new research review confirms the regimen’s success, determining that trifluridine/tipiracil plus bevacizumab was associated with improved outcomes compared to therapy solely with trifluridine/tipiracil.
 

A True Practice Changer

Now that the regimen has been on the market for more than half a year, there are longer-term data available.

Patients on average live within the same timeframe as the patients in the SUNLIGHT study, and many feel physically better on the therapy. “The combination has very quickly shifted the standard of care,” Dr. Goldberg said.

The regimen can also provide significant psychological benefits to patients.

“As patients can maintain good performance status for longer with the combination, it increases the perception of quality of life,” said Jacobo Hincapie-Echeverri, MD, a GI and geriatric oncologist at Orlando Health Cancer Institute in Orlando, Florida.

The regimen is unique too, in that it can help doctors plan additional treatment strategies.

“This current approval, for the combination of trifluridine/tipiracil and bevacizumab, is practice-changing in that it helps clarify the sequence for later treatments for patients with mCRC,” said Dr. Patel, who is also clinical director of the Center for Esophageal and Gastric Cancer and assistant professor of medicine at Harvard Medical School, Boston. “Previously, it had been difficult to decide between trifluridine/tipiracil and regorafenib in this setting.”

The fact that the regimen has been shown to give time and improved quality of life to patients in ways regorafenib does not is clarifying. “Now, with the improved outcomes seen, I do think that trifluridine/tipiracil plus bevacizumab is the better option for most mCRC patients after IV chemotherapies,” Dr. Patel added.

When it comes to his specific experience with prescribing the regimen for his patients, Dr. Patel reported that it’s easier on his patients than other therapies.

“I find that it is generally well tolerated,” he elaborated. “As an oral agent, it is also usually somewhat easier to take (than other delivery methods of medication). These factors are critical for patients who have likely already had at least 2 or 3 prior lines of chemotherapy. I have had many patients with mCRC who, after disease progression on prior IV chemotherapy regimens, have had periods of meaningful disease control – often with fewer and manageable side effects.”

Dr. Goldberg mentioned another benefit.

“The nice thing about the combination of trifluridine/tipiracil and bevacizumab is that in terms of toxicity, there’s very little difference compared to the toxicity of trifluridine/tipiracil used alone.”
 

Are There Downsides to the Regimen?

The pros are obvious, but the regimen has some cons as well. Medically, patients should have a platelet count over 75,000/mm³ and absolute neutrophil count (ANC) over 1,500/mm³ prior to the start of each cycle, and their liver and renal function should be monitored.

Patients with metastatic colorectal cancer must be also carefully monitored for hematologic adverse events (AEs) , including chemotherapy-associated neutropenia. Biweekly treatments may reduce the risk of AEs as a whole, however, according to research.

The regimen is also expensive – an approximate cost of $8,191 for a 28-day supply. According to a new study, patients managing both AE expenses along with the cost of trifluridine/tipiracil-bevacizumab face a monthly bill of about $17,179.

Some very good news, though: 100% of Medicare drug plans cover trifluridine/tipiracil, with an average copay of $57-$292. Bevacizumab is also covered by Medicare, with a copay as low as $0-$25.

Private insurers do cover the drugs, depending on a patient’s specific plan. However, if a patient’s claim is denied, financial assistance for trifluridine/tipiracil through the drug’s manufacturers may be available for some patients, reducing prescriptions to a zero cost in some cases. Bevacizumab can be made available to patients who may not have health insurance at all, too. Patients can use a financial assistance tool through the drug’s manufacturer to receive up to $25,000 in yearly copay assistance.
 

What Does the Latest Research on the Regimen Indicate?

In May 2024, two abstracts were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) that explored expanded possible use of trifluridine/tipiracil plus bevacizumab as a treatment for metastatic colorectal cancer.

The first abstract studied trifluridine/tipiracil plus bevacizumab as upfront treatment for mCRC, adding capecitabine to the regimen.

“It’s a phase 1 study looking at dose findings for the three-drug combination, where the active drug is a chemotherapy agent classified as a fluoropyrimidine ... I would characterize this as a study combining two [fluoropyrimidines] with a single targeted therapy,” Dr. Goldberg said.

“Combining two fluoropyrimidines is an unusual approach, because they tend to have overlapping side effects, and the potential is there for either innate drug resistance to the class of drugs or that the combination of two agents that work by a similar mechanism of action could hasten the development of acquired drug resistance. There is apparently a signal that combining the two chemotherapy agents enhances each other’s activity in cell culture and animal models,” he added.

Ultimately, Dr. Goldberg said he thinks more evidence is needed to prove the regimen’s effectiveness.

“This is a very early study and really provides no information about its potential given that no response data was presented,” he added. “While this is an interesting idea, it is unclear if it will pan out until we see the data on the Phase II study in progress.”

The other abstract looked at the impact of colorectal liver metastases in patients with mCRC who in phase 3 of the SUNLIGHT trial received trifluridine/tipiracil with or without bevacizumab.

“There is not much that is novel here,” Dr. Goldberg said. “The retrospective analysis shows that trifluridine/tipiracil plus bevacizumab is better than trifluridine/tipiracil alone in the subset of patients with liver metastases, as it was shown to be in the entire patient population. While this is reassuring, it’s not unexpected, especially since the vast majority of people enrolled in the SUNLIGHT trial had liver metastases.”

The Bottom Line

In the future, the potential exists for trifluridine/tipiracil combined with bevacizumab to work in first-line and second-line patients.

“Seventy percent of colorectal cancer patients reach second line treatment right now, but only 30% reach third line treatment — either they become too sick to continue, or choose not to,” Dr. Goldberg said. “The hope is that using these drugs earlier can help more patients reach and prolong treatment.”

It’s also possible that the regimen can be applied in new ways.

“Further research combining trifluridine/tipiracil and bevacizumab with other targeted therapies could yield additional advances for refractory mCRC patients,” Dr. Hincapie-Echeverri said. “The survival benefit of this therapy reinforces the importance of continuing to develop new therapies to improve outcomes in the refractory mCRC setting.”

Dr. Patel’s patient felt lucky to simply live a longer life.

Because of the regimen, “his cancer remained stable for approximately 8 months. Upon its progression, he chose not to pursue any further chemotherapy. He instead expressed his gratitude at having been able to feel more like himself for nearly a year.”

Dr. Patel received research funding in 2017 from Taiho, which manufactures trifluridine/tipiracil. He receives no current funding from Taiho and has no additional conflicts of interest. Dr. Goldberg helped represent Taiho in a patent law dispute regarding Lonsurf for which he was paid, but he is no longer paid by the company. Dr. Hincapie-Echeverri is a speaker for Astellas Pharma, which does not manufacture trifluridine/tipiracil or bevacizumab, and he has no additional conflicts of interest.

On any given day, oncologist Mark Lewis, MD, feels like he’s seesawing between two eras of technology. 

One minute, he’s working on sequencing a tumor genome. The next, he’s sifting through pages of disorganized data from a device that has been around for decades: the fax machine. 

“If two doctors’ offices aren’t on the same electronic medical record, one of the main ways to transfer records is still by fax,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “I can go from cutting-edge innovation to relying on, at best, 1980s information technology. It just boggles my mind.”

Dr. Lewis, who has posted about his frustration with fax machines, is far from alone. Oncologists are among the many specialists across the country at the mercy of telecopiers. 

According to a 2021 report by the Office of the National Coordinator for Health Information Technology, fax and mail continue to be the most common methods for hospitals and health systems to exchange care record summaries. In 2019, nearly 8 in 10 hospitals used mail or fax to send and receive health information, the report found. 

Fax machines are still commonplace across the healthcare spectrum, said Robert Havasy, MS, senior director for informatics strategy at the Healthcare Information and Management Systems Society (HIMSS). Inertia, cost, and more pressing priorities for hospitals and medical institutions contribute to the technology sticking around, he explained. 

“Post-COVID, my guess is we’re still at over 50% of healthcare practices using fax for some reason, on a daily basis,” Mr. Havasy said in an interview. “A lot of hospitals just don’t have the time, the money, or the staff to fix that problem because there’s always something a little higher up the priority chain they need to focus on.” 

If, for instance, “you’re going to do a process redesign to reduce hospital total acquired infections, your fax machine replacement might be 10th or 12th on the list. It just never gets up to 1 or 2 because it’s ‘not that much of a problem,’ ” he added.

Or is it?

Administrators may not view fax machines as a top concern, but clinicians who deal with the machines daily see it differently. 

“What worries me is we’re taking records out of an electronic storehouse [and] converting them to a paper medium,” Dr. Lewis said. “And then we are scanning into another electronic storehouse. The more steps, the more can be lost.”

And when information is lost, patient care can be compromised. 

Slower Workflows, Care Concerns

Although there are no published data on fax machine use in oncology specifically, this outdated technology does come into play in a variety of ways along the cancer care continuum. 

Radiation oncologist David R. Penberthy, MD, said patients often seek his cancer center’s expertise for second opinions, and that requires collecting patient records from many different practices. 

“Ideally, it would come electronically, but sometimes it does come by fax,” said Dr. Penberthy, program director of radiation oncology at the University of Virginia School of Medicine in Charlottesville. “The quality of the fax is not always the best. Sometimes it’s literally a fax of a fax. You’re reading something that’s very difficult to read.” 

Orders for new tests are also typically sent and received via fax temporarily while IT teams work to integrate them into the electronic health record (EHR), Dr. Penberthy said. 

Insurers and third-party laboratories often send test results back by fax as well.

“Even if I haven’t actually sent my patient out of our institution, this crucial result may only be entered back into the record as a scanned document from a fax, which is not great because it can get lost in the other results that are reported electronically,” Dr. Lewis said. The risk here is that an ordering physician won’t see these results, which can lead to delayed or overlooked care for patients, he explained.

“To me, it’s like a blind spot,” Dr. Lewis said. “Every time we use a fax, I see it actually as an opportunity for oversight and missed opportunity to collect data.”

Dr. Penberthy said faxing can slow things down at his practice, particularly if he faxes a document to another office but receives no confirmation and has to track down what happened. 

As for cybersecurity, data that are in transit during faxing are generally considered secure and compliant with the Health Insurance Portability and Accountability Act (HIPAA), said Mr. Havasy of HIMSS. However, the Privacy Rule also requires that data remain secure while at rest, which isn’t always possible, he added. 

“That’s where faxes fall down, because generally fax machines are in public, if you will, or open areas in a hospital,” he said. “They just sit on a desk. I don’t know that the next nurse who comes up and looks through that stack was the nurse who was treating the patient.” 

Important decisions or results can also be missed when sent by fax, creating headaches for physicians and care problems for patients. 

Dr. Lewis recently experienced an insurance-related fax mishap over Memorial Day weekend. He believed his patient had access to the antinausea medication he had prescribed. When Dr. Lewis happened to check the fax machine over the weekend, he found a coverage denial for the medication from the insurer but, at that point, had no recourse to appeal because it was a long holiday weekend. 

“Had the denial been sent by an electronic means that was quicker and more readily available, it would have been possible to appeal before the holiday weekend,” he said. 

Hematologist Aaron Goodman, MD, encountered a similar problem after an insurer denied coverage of an expensive cancer drug for a patient and faxed over its reason for the denial. Dr. Goodman was not directly notified that the information arrived and didn’t learn about the denial for a week, he said. 

“There’s no ‘ding’ in my inbox if something is faxed over and scanned,” said Dr. Goodman, associate professor of medicine at UC San Diego Health. “Once I realized it was denied, I was able to rectify it, but it wasted a week of a patient not getting a drug that I felt would be beneficial for them.”

Broader Health Policy Impacts

The use of outdated technology, such as fax machines, also creates ripple effects that burden the health system, health policy experts say. 

Duplicate testing and unnecessary care are top impacts, said Julia Adler-Milstein, PhD, professor of medicine and chief of the division of clinical informatics and digital transformation at the University of California, San Francisco.

Studies show that 20%-30% of the $65 billion spent annually on lab tests is used on unnecessary duplicate tests, and another estimated $30 billion is spent each year on unnecessary duplicate medical imaging. These duplicate tests may be mitigated if hospitals adopt certified EHR technology, research shows.

Still, without EHR interoperability between institutions, new providers may be unaware that tests or past labs for patients exist, leading to repeat tests, said Dr. Adler-Milstein, who researches health IT policy with a focus on EHRs. Patients can sometimes fill in the gaps, but not always. 

“Fax machines only help close information gaps if the clinician is aware of where to seek out the information and there is someone at the other organization to locate and transmit the information in a timely manner,” Dr. Adler-Milstein said. 

Old technology and poor interoperability also greatly affect data collection for disease surveillance and monitoring, said Janet Hamilton, MPH, executive director for the Council of State and Territorial Epidemiologists. This issue was keenly demonstrated during the pandemic, Ms. Hamilton said. 

“It was tragic, quite honestly,” she said. “There was such an immense amount of data that needed to be moved quickly, and that’s when computers are at their best.”

But, she said, “we didn’t have the level of systems in place to do it well.”

Specifically, the lack of electronic case reporting in place during the pandemic — where diagnoses are documented in the record and then immediately sent to the public health system — led to reports that were delayed, not made, or had missing or incomplete information, such as patients’ race and ethnicity or other health conditions, Ms. Hamilton said. 

Incomplete or missing data hampered the ability of public health officials and researchers to understand how the virus might affect different patients.

“If you had a chronic condition like cancer, you were less likely to have a positive outcome with COVID,” Ms. Hamilton said. “But because electronic case reporting was not in place, we didn’t get some of those additional pieces of information. We didn’t have people’s underlying oncology status to then say, ‘Here are individuals with these types of characteristics, and these are the things that happen if they also have a cancer.’” 

Slow, but Steady, Improvements

Efforts at the state and federal levels have targeted improved health information exchange, but progress takes time, Dr. Adler-Milstein said.

Most states have some form of health information exchange, such as statewide exchanges, regional health information organizations, or clinical data registries. Maryland is often held up as a notable example for its health information exchange, Dr. Adler-Milstein noted.

According to Maryland law, all hospitals under the jurisdiction of the Maryland Health Care Commission are required to electronically connect to the state-designated health information exchange. In 2012, Maryland became the first state to connect all its 46 acute care hospitals in the sharing of real-time data. 

The Health Information Technology for Economic and Clinical Health (HITECH) Act provided federal-enhanced Medicaid matching funds to states through 2021 to support efforts to advance electronic exchange. Nearly all states used these funds, and most have identified other sources to sustain the efforts, according to a recent US Government Accountability Office (GAO) report. However, GAO found that small and rural providers are less likely to have the financial and technological resources to participate in or maintain electronic exchange capabilities.

Nationally, several recent initiatives have targeted health data interoperability, including for cancer care. The Centers for Disease Control and Prevention’s Data Modernization Initiative is a multiyear, multi–billion-dollar effort to improve data sharing across the federal and state public health landscape. 

Meanwhile, in March 2024, the Biden-Harris administration launched United States Core Data for Interoperability Plus Cancer. The program will define a recommended minimum set of cancer-related data to be included in a patient’s EHR to enhance data exchange for research and clinical care. 

EHR vendors are also key to improving the landscape, said Dr. Adler-Milstein. Vendors such as Epic have developed strong sharing capabilities for transmitting health information from site to site, but of course, that only helps if providers have Epic, she said. 

“That’s where these national frameworks should help, because we don’t want it to break down by what EHR vendor you have,” she said. “It’s a patchwork. You can go to some places and hear success stories because they have Epic or a state health information exchange, but it’s very heterogeneous. In some places, they have nothing and are using a fax machine.”

Mr. Havasy believes fax machines will ultimately go extinct, particularly as a younger, more digitally savvy generation enters the healthcare workforce. He also foresees that the growing use of artificial intelligence will help eradicate the outdated technology. 

But, Ms. Hamilton noted, “unless we have consistent, ongoing, sustained funding, it is very hard to move off [an older] technology that can work. That’s one of the biggest barriers.” 

“Public health is about protecting the lives of every single person everywhere,” Ms. Hamilton said, “but when we don’t have the data that comes into the system, we can’t achieve our mission.”
 

A version of this article appeared on Medscape.com.

On any given day, oncologist Mark Lewis, MD, feels like he’s seesawing between two eras of technology. 

One minute, he’s working on sequencing a tumor genome. The next, he’s sifting through pages of disorganized data from a device that has been around for decades: the fax machine. 

“If two doctors’ offices aren’t on the same electronic medical record, one of the main ways to transfer records is still by fax,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “I can go from cutting-edge innovation to relying on, at best, 1980s information technology. It just boggles my mind.”

Dr. Lewis, who has posted about his frustration with fax machines, is far from alone. Oncologists are among the many specialists across the country at the mercy of telecopiers. 

According to a 2021 report by the Office of the National Coordinator for Health Information Technology, fax and mail continue to be the most common methods for hospitals and health systems to exchange care record summaries. In 2019, nearly 8 in 10 hospitals used mail or fax to send and receive health information, the report found. 

Fax machines are still commonplace across the healthcare spectrum, said Robert Havasy, MS, senior director for informatics strategy at the Healthcare Information and Management Systems Society (HIMSS). Inertia, cost, and more pressing priorities for hospitals and medical institutions contribute to the technology sticking around, he explained. 

“Post-COVID, my guess is we’re still at over 50% of healthcare practices using fax for some reason, on a daily basis,” Mr. Havasy said in an interview. “A lot of hospitals just don’t have the time, the money, or the staff to fix that problem because there’s always something a little higher up the priority chain they need to focus on.” 

If, for instance, “you’re going to do a process redesign to reduce hospital total acquired infections, your fax machine replacement might be 10th or 12th on the list. It just never gets up to 1 or 2 because it’s ‘not that much of a problem,’ ” he added.

Or is it?

Administrators may not view fax machines as a top concern, but clinicians who deal with the machines daily see it differently. 

“What worries me is we’re taking records out of an electronic storehouse [and] converting them to a paper medium,” Dr. Lewis said. “And then we are scanning into another electronic storehouse. The more steps, the more can be lost.”

And when information is lost, patient care can be compromised. 

Slower Workflows, Care Concerns

Although there are no published data on fax machine use in oncology specifically, this outdated technology does come into play in a variety of ways along the cancer care continuum. 

Radiation oncologist David R. Penberthy, MD, said patients often seek his cancer center’s expertise for second opinions, and that requires collecting patient records from many different practices. 

“Ideally, it would come electronically, but sometimes it does come by fax,” said Dr. Penberthy, program director of radiation oncology at the University of Virginia School of Medicine in Charlottesville. “The quality of the fax is not always the best. Sometimes it’s literally a fax of a fax. You’re reading something that’s very difficult to read.” 

Orders for new tests are also typically sent and received via fax temporarily while IT teams work to integrate them into the electronic health record (EHR), Dr. Penberthy said. 

Insurers and third-party laboratories often send test results back by fax as well.

“Even if I haven’t actually sent my patient out of our institution, this crucial result may only be entered back into the record as a scanned document from a fax, which is not great because it can get lost in the other results that are reported electronically,” Dr. Lewis said. The risk here is that an ordering physician won’t see these results, which can lead to delayed or overlooked care for patients, he explained.

“To me, it’s like a blind spot,” Dr. Lewis said. “Every time we use a fax, I see it actually as an opportunity for oversight and missed opportunity to collect data.”

Dr. Penberthy said faxing can slow things down at his practice, particularly if he faxes a document to another office but receives no confirmation and has to track down what happened. 

As for cybersecurity, data that are in transit during faxing are generally considered secure and compliant with the Health Insurance Portability and Accountability Act (HIPAA), said Mr. Havasy of HIMSS. However, the Privacy Rule also requires that data remain secure while at rest, which isn’t always possible, he added. 

“That’s where faxes fall down, because generally fax machines are in public, if you will, or open areas in a hospital,” he said. “They just sit on a desk. I don’t know that the next nurse who comes up and looks through that stack was the nurse who was treating the patient.” 

Important decisions or results can also be missed when sent by fax, creating headaches for physicians and care problems for patients. 

Dr. Lewis recently experienced an insurance-related fax mishap over Memorial Day weekend. He believed his patient had access to the antinausea medication he had prescribed. When Dr. Lewis happened to check the fax machine over the weekend, he found a coverage denial for the medication from the insurer but, at that point, had no recourse to appeal because it was a long holiday weekend. 

“Had the denial been sent by an electronic means that was quicker and more readily available, it would have been possible to appeal before the holiday weekend,” he said. 

Hematologist Aaron Goodman, MD, encountered a similar problem after an insurer denied coverage of an expensive cancer drug for a patient and faxed over its reason for the denial. Dr. Goodman was not directly notified that the information arrived and didn’t learn about the denial for a week, he said. 

“There’s no ‘ding’ in my inbox if something is faxed over and scanned,” said Dr. Goodman, associate professor of medicine at UC San Diego Health. “Once I realized it was denied, I was able to rectify it, but it wasted a week of a patient not getting a drug that I felt would be beneficial for them.”

Broader Health Policy Impacts

The use of outdated technology, such as fax machines, also creates ripple effects that burden the health system, health policy experts say. 

Duplicate testing and unnecessary care are top impacts, said Julia Adler-Milstein, PhD, professor of medicine and chief of the division of clinical informatics and digital transformation at the University of California, San Francisco.

Studies show that 20%-30% of the $65 billion spent annually on lab tests is used on unnecessary duplicate tests, and another estimated $30 billion is spent each year on unnecessary duplicate medical imaging. These duplicate tests may be mitigated if hospitals adopt certified EHR technology, research shows.

Still, without EHR interoperability between institutions, new providers may be unaware that tests or past labs for patients exist, leading to repeat tests, said Dr. Adler-Milstein, who researches health IT policy with a focus on EHRs. Patients can sometimes fill in the gaps, but not always. 

“Fax machines only help close information gaps if the clinician is aware of where to seek out the information and there is someone at the other organization to locate and transmit the information in a timely manner,” Dr. Adler-Milstein said. 

Old technology and poor interoperability also greatly affect data collection for disease surveillance and monitoring, said Janet Hamilton, MPH, executive director for the Council of State and Territorial Epidemiologists. This issue was keenly demonstrated during the pandemic, Ms. Hamilton said. 

“It was tragic, quite honestly,” she said. “There was such an immense amount of data that needed to be moved quickly, and that’s when computers are at their best.”

But, she said, “we didn’t have the level of systems in place to do it well.”

Specifically, the lack of electronic case reporting in place during the pandemic — where diagnoses are documented in the record and then immediately sent to the public health system — led to reports that were delayed, not made, or had missing or incomplete information, such as patients’ race and ethnicity or other health conditions, Ms. Hamilton said. 

Incomplete or missing data hampered the ability of public health officials and researchers to understand how the virus might affect different patients.

“If you had a chronic condition like cancer, you were less likely to have a positive outcome with COVID,” Ms. Hamilton said. “But because electronic case reporting was not in place, we didn’t get some of those additional pieces of information. We didn’t have people’s underlying oncology status to then say, ‘Here are individuals with these types of characteristics, and these are the things that happen if they also have a cancer.’” 

Slow, but Steady, Improvements

Efforts at the state and federal levels have targeted improved health information exchange, but progress takes time, Dr. Adler-Milstein said.

Most states have some form of health information exchange, such as statewide exchanges, regional health information organizations, or clinical data registries. Maryland is often held up as a notable example for its health information exchange, Dr. Adler-Milstein noted.

According to Maryland law, all hospitals under the jurisdiction of the Maryland Health Care Commission are required to electronically connect to the state-designated health information exchange. In 2012, Maryland became the first state to connect all its 46 acute care hospitals in the sharing of real-time data. 

The Health Information Technology for Economic and Clinical Health (HITECH) Act provided federal-enhanced Medicaid matching funds to states through 2021 to support efforts to advance electronic exchange. Nearly all states used these funds, and most have identified other sources to sustain the efforts, according to a recent US Government Accountability Office (GAO) report. However, GAO found that small and rural providers are less likely to have the financial and technological resources to participate in or maintain electronic exchange capabilities.

Nationally, several recent initiatives have targeted health data interoperability, including for cancer care. The Centers for Disease Control and Prevention’s Data Modernization Initiative is a multiyear, multi–billion-dollar effort to improve data sharing across the federal and state public health landscape. 

Meanwhile, in March 2024, the Biden-Harris administration launched United States Core Data for Interoperability Plus Cancer. The program will define a recommended minimum set of cancer-related data to be included in a patient’s EHR to enhance data exchange for research and clinical care. 

EHR vendors are also key to improving the landscape, said Dr. Adler-Milstein. Vendors such as Epic have developed strong sharing capabilities for transmitting health information from site to site, but of course, that only helps if providers have Epic, she said. 

“That’s where these national frameworks should help, because we don’t want it to break down by what EHR vendor you have,” she said. “It’s a patchwork. You can go to some places and hear success stories because they have Epic or a state health information exchange, but it’s very heterogeneous. In some places, they have nothing and are using a fax machine.”

Mr. Havasy believes fax machines will ultimately go extinct, particularly as a younger, more digitally savvy generation enters the healthcare workforce. He also foresees that the growing use of artificial intelligence will help eradicate the outdated technology. 

But, Ms. Hamilton noted, “unless we have consistent, ongoing, sustained funding, it is very hard to move off [an older] technology that can work. That’s one of the biggest barriers.” 

“Public health is about protecting the lives of every single person everywhere,” Ms. Hamilton said, “but when we don’t have the data that comes into the system, we can’t achieve our mission.”
 

A version of this article appeared on Medscape.com.

On any given day, oncologist Mark Lewis, MD, feels like he’s seesawing between two eras of technology. 

One minute, he’s working on sequencing a tumor genome. The next, he’s sifting through pages of disorganized data from a device that has been around for decades: the fax machine. 

“If two doctors’ offices aren’t on the same electronic medical record, one of the main ways to transfer records is still by fax,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Healthcare in Murray, Utah. “I can go from cutting-edge innovation to relying on, at best, 1980s information technology. It just boggles my mind.”

Dr. Lewis, who has posted about his frustration with fax machines, is far from alone. Oncologists are among the many specialists across the country at the mercy of telecopiers. 

According to a 2021 report by the Office of the National Coordinator for Health Information Technology, fax and mail continue to be the most common methods for hospitals and health systems to exchange care record summaries. In 2019, nearly 8 in 10 hospitals used mail or fax to send and receive health information, the report found. 

Fax machines are still commonplace across the healthcare spectrum, said Robert Havasy, MS, senior director for informatics strategy at the Healthcare Information and Management Systems Society (HIMSS). Inertia, cost, and more pressing priorities for hospitals and medical institutions contribute to the technology sticking around, he explained. 

“Post-COVID, my guess is we’re still at over 50% of healthcare practices using fax for some reason, on a daily basis,” Mr. Havasy said in an interview. “A lot of hospitals just don’t have the time, the money, or the staff to fix that problem because there’s always something a little higher up the priority chain they need to focus on.” 

If, for instance, “you’re going to do a process redesign to reduce hospital total acquired infections, your fax machine replacement might be 10th or 12th on the list. It just never gets up to 1 or 2 because it’s ‘not that much of a problem,’ ” he added.

Or is it?

Administrators may not view fax machines as a top concern, but clinicians who deal with the machines daily see it differently. 

“What worries me is we’re taking records out of an electronic storehouse [and] converting them to a paper medium,” Dr. Lewis said. “And then we are scanning into another electronic storehouse. The more steps, the more can be lost.”

And when information is lost, patient care can be compromised. 

Slower Workflows, Care Concerns

Although there are no published data on fax machine use in oncology specifically, this outdated technology does come into play in a variety of ways along the cancer care continuum. 

Radiation oncologist David R. Penberthy, MD, said patients often seek his cancer center’s expertise for second opinions, and that requires collecting patient records from many different practices. 

“Ideally, it would come electronically, but sometimes it does come by fax,” said Dr. Penberthy, program director of radiation oncology at the University of Virginia School of Medicine in Charlottesville. “The quality of the fax is not always the best. Sometimes it’s literally a fax of a fax. You’re reading something that’s very difficult to read.” 

Orders for new tests are also typically sent and received via fax temporarily while IT teams work to integrate them into the electronic health record (EHR), Dr. Penberthy said. 

Insurers and third-party laboratories often send test results back by fax as well.

“Even if I haven’t actually sent my patient out of our institution, this crucial result may only be entered back into the record as a scanned document from a fax, which is not great because it can get lost in the other results that are reported electronically,” Dr. Lewis said. The risk here is that an ordering physician won’t see these results, which can lead to delayed or overlooked care for patients, he explained.

“To me, it’s like a blind spot,” Dr. Lewis said. “Every time we use a fax, I see it actually as an opportunity for oversight and missed opportunity to collect data.”

Dr. Penberthy said faxing can slow things down at his practice, particularly if he faxes a document to another office but receives no confirmation and has to track down what happened. 

As for cybersecurity, data that are in transit during faxing are generally considered secure and compliant with the Health Insurance Portability and Accountability Act (HIPAA), said Mr. Havasy of HIMSS. However, the Privacy Rule also requires that data remain secure while at rest, which isn’t always possible, he added. 

“That’s where faxes fall down, because generally fax machines are in public, if you will, or open areas in a hospital,” he said. “They just sit on a desk. I don’t know that the next nurse who comes up and looks through that stack was the nurse who was treating the patient.” 

Important decisions or results can also be missed when sent by fax, creating headaches for physicians and care problems for patients. 

Dr. Lewis recently experienced an insurance-related fax mishap over Memorial Day weekend. He believed his patient had access to the antinausea medication he had prescribed. When Dr. Lewis happened to check the fax machine over the weekend, he found a coverage denial for the medication from the insurer but, at that point, had no recourse to appeal because it was a long holiday weekend. 

“Had the denial been sent by an electronic means that was quicker and more readily available, it would have been possible to appeal before the holiday weekend,” he said. 

Hematologist Aaron Goodman, MD, encountered a similar problem after an insurer denied coverage of an expensive cancer drug for a patient and faxed over its reason for the denial. Dr. Goodman was not directly notified that the information arrived and didn’t learn about the denial for a week, he said. 

“There’s no ‘ding’ in my inbox if something is faxed over and scanned,” said Dr. Goodman, associate professor of medicine at UC San Diego Health. “Once I realized it was denied, I was able to rectify it, but it wasted a week of a patient not getting a drug that I felt would be beneficial for them.”

Broader Health Policy Impacts

The use of outdated technology, such as fax machines, also creates ripple effects that burden the health system, health policy experts say. 

Duplicate testing and unnecessary care are top impacts, said Julia Adler-Milstein, PhD, professor of medicine and chief of the division of clinical informatics and digital transformation at the University of California, San Francisco.

Studies show that 20%-30% of the $65 billion spent annually on lab tests is used on unnecessary duplicate tests, and another estimated $30 billion is spent each year on unnecessary duplicate medical imaging. These duplicate tests may be mitigated if hospitals adopt certified EHR technology, research shows.

Still, without EHR interoperability between institutions, new providers may be unaware that tests or past labs for patients exist, leading to repeat tests, said Dr. Adler-Milstein, who researches health IT policy with a focus on EHRs. Patients can sometimes fill in the gaps, but not always. 

“Fax machines only help close information gaps if the clinician is aware of where to seek out the information and there is someone at the other organization to locate and transmit the information in a timely manner,” Dr. Adler-Milstein said. 

Old technology and poor interoperability also greatly affect data collection for disease surveillance and monitoring, said Janet Hamilton, MPH, executive director for the Council of State and Territorial Epidemiologists. This issue was keenly demonstrated during the pandemic, Ms. Hamilton said. 

“It was tragic, quite honestly,” she said. “There was such an immense amount of data that needed to be moved quickly, and that’s when computers are at their best.”

But, she said, “we didn’t have the level of systems in place to do it well.”

Specifically, the lack of electronic case reporting in place during the pandemic — where diagnoses are documented in the record and then immediately sent to the public health system — led to reports that were delayed, not made, or had missing or incomplete information, such as patients’ race and ethnicity or other health conditions, Ms. Hamilton said. 

Incomplete or missing data hampered the ability of public health officials and researchers to understand how the virus might affect different patients.

“If you had a chronic condition like cancer, you were less likely to have a positive outcome with COVID,” Ms. Hamilton said. “But because electronic case reporting was not in place, we didn’t get some of those additional pieces of information. We didn’t have people’s underlying oncology status to then say, ‘Here are individuals with these types of characteristics, and these are the things that happen if they also have a cancer.’” 

Slow, but Steady, Improvements

Efforts at the state and federal levels have targeted improved health information exchange, but progress takes time, Dr. Adler-Milstein said.

Most states have some form of health information exchange, such as statewide exchanges, regional health information organizations, or clinical data registries. Maryland is often held up as a notable example for its health information exchange, Dr. Adler-Milstein noted.

According to Maryland law, all hospitals under the jurisdiction of the Maryland Health Care Commission are required to electronically connect to the state-designated health information exchange. In 2012, Maryland became the first state to connect all its 46 acute care hospitals in the sharing of real-time data. 

The Health Information Technology for Economic and Clinical Health (HITECH) Act provided federal-enhanced Medicaid matching funds to states through 2021 to support efforts to advance electronic exchange. Nearly all states used these funds, and most have identified other sources to sustain the efforts, according to a recent US Government Accountability Office (GAO) report. However, GAO found that small and rural providers are less likely to have the financial and technological resources to participate in or maintain electronic exchange capabilities.

Nationally, several recent initiatives have targeted health data interoperability, including for cancer care. The Centers for Disease Control and Prevention’s Data Modernization Initiative is a multiyear, multi–billion-dollar effort to improve data sharing across the federal and state public health landscape. 

Meanwhile, in March 2024, the Biden-Harris administration launched United States Core Data for Interoperability Plus Cancer. The program will define a recommended minimum set of cancer-related data to be included in a patient’s EHR to enhance data exchange for research and clinical care. 

EHR vendors are also key to improving the landscape, said Dr. Adler-Milstein. Vendors such as Epic have developed strong sharing capabilities for transmitting health information from site to site, but of course, that only helps if providers have Epic, she said. 

“That’s where these national frameworks should help, because we don’t want it to break down by what EHR vendor you have,” she said. “It’s a patchwork. You can go to some places and hear success stories because they have Epic or a state health information exchange, but it’s very heterogeneous. In some places, they have nothing and are using a fax machine.”

Mr. Havasy believes fax machines will ultimately go extinct, particularly as a younger, more digitally savvy generation enters the healthcare workforce. He also foresees that the growing use of artificial intelligence will help eradicate the outdated technology. 

But, Ms. Hamilton noted, “unless we have consistent, ongoing, sustained funding, it is very hard to move off [an older] technology that can work. That’s one of the biggest barriers.” 

“Public health is about protecting the lives of every single person everywhere,” Ms. Hamilton said, “but when we don’t have the data that comes into the system, we can’t achieve our mission.”
 

A version of this article appeared on Medscape.com.

Results from the latest survey by the National Comprehensive Cancer Network (NCCN) showed that numerous critical systemic anticancer therapies, primarily generic drugs, are currently in shortage.

Nearly 90% of the 28 NCCN member centers who responded to the survey, conducted between May 28 and June 11, said they were experiencing a shortage of at least one drug.

“Many drugs that are currently in shortage form the backbones of effective multiagent regimens across both curative and palliative treatment settings,” NCCN’s CEO Crystal S. Denlinger, MD, said in an interview.

The good news is that carboplatin and cisplatin shortages have fallen dramatically since 2023. At the peak of the shortage in 2023, 93% of centers surveyed reported experiencing a shortage of carboplatin and 70% were experiencing a shortage of cisplatin, whereas in 2024, only 11% reported a carboplatin shortage and 7% reported a cisplatin shortage.

“Thankfully, the shortages for carboplatin and cisplatin are mostly resolved at this time,” Dr. Denlinger said.

However, all three NCCN surveys conducted in the past year, including the most recent one, have found shortages of various chemotherapies and supportive care medications, which suggests this is an ongoing issue affecting a significant spectrum of generic drugs.

“The acute crisis associated with the shortage of carboplatin and cisplatin was a singular event that brought the issue into the national spotlight,” but it’s “important to note that the current broad drug shortages found on this survey are not new,” said Dr. Denlinger.

In the latest survey, 89% of NCCN centers continue to report shortages of one or more drugs, and 75% said they are experiencing shortages of two or more drugs.

Overall, 57% of centers are short on vinblastine, 46% are short on etoposide, and 43% are short on topotecan. Other common chemotherapy and supportive care agents in short supply include dacarbazine (18% of centers) as well as 5-fluorouracil (5-FU) and methotrexate (14% of centers).

In 2023, however, shortages of methotrexate and 5-FU were worse, with 67% of centers reporting shortages of methotrexate and 26% of 5-FU.

In the current survey, 75% of NCCN centers also noted they were aware of drug shortages within community practices in their area, and more than one in four centers reported treatment delays requiring additional prior authorization.

Cancer drug shortages impact not only routine treatments but also clinical trials. The recent survey found that 43% of respondents said drug shortages disrupted clinical trials at their center. The biggest issues centers flagged included greater administrative burdens, lower patient enrollment, and fewer open trials.

How are centers dealing with ongoing supply issues?

Top mitigation strategies include reducing waste, limiting use of current stock, and adjusting the timing and dosage within evidence-based ranges.

“The current situation underscores the need for sustainable, long-term solutions that ensure a stable supply of high-quality cancer medications,” Alyssa Schatz, MSW, NCCN senior director of policy and advocacy, said in a news release.

Three-quarters (75%) of survey respondents said they would like to see economic incentives put in place to encourage the high-quality manufacturing of medications, especially generic versions that are often in short supply. Nearly two-thirds (64%) cited a need for a broader buffer stock payment, and the same percentage would like to see more information on user experiences with various generic suppliers to help hospitals contract with those engaging in high-quality practices.

The NCCN also continues to work with federal regulators, agencies, and lawmakers to implement long-term solutions to cancer drug shortages.

“The federal government has a key role to play in addressing this issue,” Ms. Schatz said. “Establishing economic incentives, such as tax breaks or manufacturing grants for generic drugmakers, will help support a robust and resilient supply chain — ultimately safeguarding care for people with cancer across the country.”

A version of this article appeared on Medscape.com.

Results from the latest survey by the National Comprehensive Cancer Network (NCCN) showed that numerous critical systemic anticancer therapies, primarily generic drugs, are currently in shortage.

Nearly 90% of the 28 NCCN member centers who responded to the survey, conducted between May 28 and June 11, said they were experiencing a shortage of at least one drug.

“Many drugs that are currently in shortage form the backbones of effective multiagent regimens across both curative and palliative treatment settings,” NCCN’s CEO Crystal S. Denlinger, MD, said in an interview.

The good news is that carboplatin and cisplatin shortages have fallen dramatically since 2023. At the peak of the shortage in 2023, 93% of centers surveyed reported experiencing a shortage of carboplatin and 70% were experiencing a shortage of cisplatin, whereas in 2024, only 11% reported a carboplatin shortage and 7% reported a cisplatin shortage.

“Thankfully, the shortages for carboplatin and cisplatin are mostly resolved at this time,” Dr. Denlinger said.

However, all three NCCN surveys conducted in the past year, including the most recent one, have found shortages of various chemotherapies and supportive care medications, which suggests this is an ongoing issue affecting a significant spectrum of generic drugs.

“The acute crisis associated with the shortage of carboplatin and cisplatin was a singular event that brought the issue into the national spotlight,” but it’s “important to note that the current broad drug shortages found on this survey are not new,” said Dr. Denlinger.

In the latest survey, 89% of NCCN centers continue to report shortages of one or more drugs, and 75% said they are experiencing shortages of two or more drugs.

Overall, 57% of centers are short on vinblastine, 46% are short on etoposide, and 43% are short on topotecan. Other common chemotherapy and supportive care agents in short supply include dacarbazine (18% of centers) as well as 5-fluorouracil (5-FU) and methotrexate (14% of centers).

In 2023, however, shortages of methotrexate and 5-FU were worse, with 67% of centers reporting shortages of methotrexate and 26% of 5-FU.

In the current survey, 75% of NCCN centers also noted they were aware of drug shortages within community practices in their area, and more than one in four centers reported treatment delays requiring additional prior authorization.

Cancer drug shortages impact not only routine treatments but also clinical trials. The recent survey found that 43% of respondents said drug shortages disrupted clinical trials at their center. The biggest issues centers flagged included greater administrative burdens, lower patient enrollment, and fewer open trials.

How are centers dealing with ongoing supply issues?

Top mitigation strategies include reducing waste, limiting use of current stock, and adjusting the timing and dosage within evidence-based ranges.

“The current situation underscores the need for sustainable, long-term solutions that ensure a stable supply of high-quality cancer medications,” Alyssa Schatz, MSW, NCCN senior director of policy and advocacy, said in a news release.

Three-quarters (75%) of survey respondents said they would like to see economic incentives put in place to encourage the high-quality manufacturing of medications, especially generic versions that are often in short supply. Nearly two-thirds (64%) cited a need for a broader buffer stock payment, and the same percentage would like to see more information on user experiences with various generic suppliers to help hospitals contract with those engaging in high-quality practices.

The NCCN also continues to work with federal regulators, agencies, and lawmakers to implement long-term solutions to cancer drug shortages.

“The federal government has a key role to play in addressing this issue,” Ms. Schatz said. “Establishing economic incentives, such as tax breaks or manufacturing grants for generic drugmakers, will help support a robust and resilient supply chain — ultimately safeguarding care for people with cancer across the country.”

A version of this article appeared on Medscape.com.

Results from the latest survey by the National Comprehensive Cancer Network (NCCN) showed that numerous critical systemic anticancer therapies, primarily generic drugs, are currently in shortage.

Nearly 90% of the 28 NCCN member centers who responded to the survey, conducted between May 28 and June 11, said they were experiencing a shortage of at least one drug.

“Many drugs that are currently in shortage form the backbones of effective multiagent regimens across both curative and palliative treatment settings,” NCCN’s CEO Crystal S. Denlinger, MD, said in an interview.

The good news is that carboplatin and cisplatin shortages have fallen dramatically since 2023. At the peak of the shortage in 2023, 93% of centers surveyed reported experiencing a shortage of carboplatin and 70% were experiencing a shortage of cisplatin, whereas in 2024, only 11% reported a carboplatin shortage and 7% reported a cisplatin shortage.

“Thankfully, the shortages for carboplatin and cisplatin are mostly resolved at this time,” Dr. Denlinger said.

However, all three NCCN surveys conducted in the past year, including the most recent one, have found shortages of various chemotherapies and supportive care medications, which suggests this is an ongoing issue affecting a significant spectrum of generic drugs.

“The acute crisis associated with the shortage of carboplatin and cisplatin was a singular event that brought the issue into the national spotlight,” but it’s “important to note that the current broad drug shortages found on this survey are not new,” said Dr. Denlinger.

In the latest survey, 89% of NCCN centers continue to report shortages of one or more drugs, and 75% said they are experiencing shortages of two or more drugs.

Overall, 57% of centers are short on vinblastine, 46% are short on etoposide, and 43% are short on topotecan. Other common chemotherapy and supportive care agents in short supply include dacarbazine (18% of centers) as well as 5-fluorouracil (5-FU) and methotrexate (14% of centers).

In 2023, however, shortages of methotrexate and 5-FU were worse, with 67% of centers reporting shortages of methotrexate and 26% of 5-FU.

In the current survey, 75% of NCCN centers also noted they were aware of drug shortages within community practices in their area, and more than one in four centers reported treatment delays requiring additional prior authorization.

Cancer drug shortages impact not only routine treatments but also clinical trials. The recent survey found that 43% of respondents said drug shortages disrupted clinical trials at their center. The biggest issues centers flagged included greater administrative burdens, lower patient enrollment, and fewer open trials.

How are centers dealing with ongoing supply issues?

Top mitigation strategies include reducing waste, limiting use of current stock, and adjusting the timing and dosage within evidence-based ranges.

“The current situation underscores the need for sustainable, long-term solutions that ensure a stable supply of high-quality cancer medications,” Alyssa Schatz, MSW, NCCN senior director of policy and advocacy, said in a news release.

Three-quarters (75%) of survey respondents said they would like to see economic incentives put in place to encourage the high-quality manufacturing of medications, especially generic versions that are often in short supply. Nearly two-thirds (64%) cited a need for a broader buffer stock payment, and the same percentage would like to see more information on user experiences with various generic suppliers to help hospitals contract with those engaging in high-quality practices.

The NCCN also continues to work with federal regulators, agencies, and lawmakers to implement long-term solutions to cancer drug shortages.

“The federal government has a key role to play in addressing this issue,” Ms. Schatz said. “Establishing economic incentives, such as tax breaks or manufacturing grants for generic drugmakers, will help support a robust and resilient supply chain — ultimately safeguarding care for people with cancer across the country.”

A version of this article appeared on Medscape.com.

Experts say the US Supreme Court’s ruling Friday to overturn the decades-old “Chevron doctrine” could severely restrict the ability of federal agencies to regulate all aspects of healthcare.

Larry Levitt, executive vice president for health policy at the Kaiser Family Foundation, wrote on X, “my worry is that it will paralyze policymaking in healthcare and other areas,” because “Congress will try to fill in more details, making it harder to pass legislation.” He also wrote that federal agencies “will become very cautious in using their regulatory authority.”

In their 6-3 opinion reversing the “Chevron doctrine” — which has been followed since a 1984 Court opinion — the Justices said that the judiciary should no longer have to defer to federal agency interpretations of laws. Existing federal law “requires courts to exercise their independent judgment in deciding whether an agency has acted within its statutory authority,” said the Court, in stating why Chevron should be overruled.

Writing for the majority in the combined cases — Relentless v. Department of Commerce and Loper Bright Enterprises v. Raimondo — Chief Justice John Roberts Jr. wrote that “agencies have no special competence in resolving statutory ambiguities. Courts do.”

In a dissenting opinion, Justice Elena Kagan said the decision was a judicial power grab and would result in a “jolt to the legal system.” She was joined by Justices Sonia Sotomayor and Ketanji Brown Jackson.

The opinion will have many repercussions, said lawyer and Supreme Court watcher Amy Howe. The Chevron ruling has been “one of the most important rulings on federal administrative law, cited by federal courts more than 18,000 times,” she wrote on her blog.

For example, without the long-standing deference to agencies under Chevron, healthcare providers may have more opportunities to challenge how federal officials set Medicare reimbursement for hospital procedures or prescription drugs, Baker Donelson healthcare attorneys McKenna Cloud and Thomas Barnard wrote in an analysis.

Seventeen health organizations issued a joint statement signaling their disappointment. 

“We anticipate that today’s ruling will cause significant disruption to publicly funded health insurance programs, to the stability of this country’s healthcare and food and drug review systems, and to the health and well-being of the patients and consumers we serve,” wrote the organizations, which included American Academy of Pediatrics, American Cancer Society, American Cancer Society Cancer Action Network, ALS Association, American Heart Association, American Lung Association, American Public Health Association, American Thoracic Society, Bazelon Center for Mental Health Law, Campaign for Tobacco-Free Kids, Child Neurology Foundation, Epilepsy Foundation, Muscular Dystrophy Association, National Health Law Program, Physicians for Social Responsibility, The Leukemia & Lymphoma Society, and Truth Initiative.

“It’s much harder for agencies to exercise power without some power to interpret statues. This is big,” wrote Berkeley Law Professor Orin Kerr on X.
 

A New, Uncertain Landscape for Healthcare

In the original Chevron case, the Court ruled that federal agencies had relevant expertise and should be given deference in resolving ambiguities that Congress had not spelled out in legislation.

In Relentless and Loper Bright, the plaintiffs argued that federal agencies overstepped their authority by issuing a rule that required commercial fishing vessels to pay for professional observers to monitor their catch.

In a statement after Friday’s ruling, the Relentless plaintiffs’ attorneys said that the decision “will recalibrate the balance of power between agencies and courts” and “make it harder for those agencies to adopt regulatory programs that exceed the authority conferred on them by Congress.”

Some predicted chaos in the wake of the ruling.

“Overturning Chevron could invite legal challenges to any and all agency determinations of ambiguous statutes by any stakeholder, leaving individual courts with the impractical task of determining the ‘correct’ meaning of statutes without the benefit of requisite expertise, practical experience, or public engagement,” wrote Sahil Agrawal, MD, PhD, Joseph S. Ross, MD, and Reshma Ramachandran, MD, in JAMA in an opinion piece in March that considered the ramifications of overturning Chevron.

“The spillover effects for medicine and public health, in turn, will be consequential,” they wrote.

In an analysis published in April, the Kaiser Family Foundation noted many potential ramifications on patient and consumer protections in the health insurance market. For instance, courts could vacate current rules governing protections under the Affordable Care Act, including that health plans offer a range of free preventive health services, such as breast, cervical, colon, and lung cancer screening.
 

Congressional, White House Reaction

Many legal observers said the ruling will have the effect of requiring Congress to write ever-more dense and exacting legislation to prevent agencies from interpreting any gaps.

Some members of Congress welcomed the decision.

Senate Minority Leader Mitch McConnell (R-Kentucky) said in a statement, “The Constitution vests Congress with the sole authority to make law,” adding, “the Supreme Court made it clear today that our system of government leaves no room for an unelected bureaucracy to co-opt this authority for itself.”

In a post on X, Senate Majority Leader Chuck Schumer (D-New York) accused the Court of siding with “special interests and giant corporations.” Added Mr. Schumer, “Their headlong rush to overturn 40 years of precedent and impose their own radical views is appalling.”

White House Press Secretary Karine Jean-Pierre said in a statement that “While this decision undermines the ability of federal agencies to use their expertise as Congress intended to make government work for the people, the Biden-Harris Administration will not relent in our efforts to protect and serve every American.”

A version of this article first appeared on Medscape.com.

Experts say the US Supreme Court’s ruling Friday to overturn the decades-old “Chevron doctrine” could severely restrict the ability of federal agencies to regulate all aspects of healthcare.

Larry Levitt, executive vice president for health policy at the Kaiser Family Foundation, wrote on X, “my worry is that it will paralyze policymaking in healthcare and other areas,” because “Congress will try to fill in more details, making it harder to pass legislation.” He also wrote that federal agencies “will become very cautious in using their regulatory authority.”

In their 6-3 opinion reversing the “Chevron doctrine” — which has been followed since a 1984 Court opinion — the Justices said that the judiciary should no longer have to defer to federal agency interpretations of laws. Existing federal law “requires courts to exercise their independent judgment in deciding whether an agency has acted within its statutory authority,” said the Court, in stating why Chevron should be overruled.

Writing for the majority in the combined cases — Relentless v. Department of Commerce and Loper Bright Enterprises v. Raimondo — Chief Justice John Roberts Jr. wrote that “agencies have no special competence in resolving statutory ambiguities. Courts do.”

In a dissenting opinion, Justice Elena Kagan said the decision was a judicial power grab and would result in a “jolt to the legal system.” She was joined by Justices Sonia Sotomayor and Ketanji Brown Jackson.

The opinion will have many repercussions, said lawyer and Supreme Court watcher Amy Howe. The Chevron ruling has been “one of the most important rulings on federal administrative law, cited by federal courts more than 18,000 times,” she wrote on her blog.

For example, without the long-standing deference to agencies under Chevron, healthcare providers may have more opportunities to challenge how federal officials set Medicare reimbursement for hospital procedures or prescription drugs, Baker Donelson healthcare attorneys McKenna Cloud and Thomas Barnard wrote in an analysis.

Seventeen health organizations issued a joint statement signaling their disappointment. 

“We anticipate that today’s ruling will cause significant disruption to publicly funded health insurance programs, to the stability of this country’s healthcare and food and drug review systems, and to the health and well-being of the patients and consumers we serve,” wrote the organizations, which included American Academy of Pediatrics, American Cancer Society, American Cancer Society Cancer Action Network, ALS Association, American Heart Association, American Lung Association, American Public Health Association, American Thoracic Society, Bazelon Center for Mental Health Law, Campaign for Tobacco-Free Kids, Child Neurology Foundation, Epilepsy Foundation, Muscular Dystrophy Association, National Health Law Program, Physicians for Social Responsibility, The Leukemia & Lymphoma Society, and Truth Initiative.

“It’s much harder for agencies to exercise power without some power to interpret statues. This is big,” wrote Berkeley Law Professor Orin Kerr on X.
 

A New, Uncertain Landscape for Healthcare

In the original Chevron case, the Court ruled that federal agencies had relevant expertise and should be given deference in resolving ambiguities that Congress had not spelled out in legislation.

In Relentless and Loper Bright, the plaintiffs argued that federal agencies overstepped their authority by issuing a rule that required commercial fishing vessels to pay for professional observers to monitor their catch.

In a statement after Friday’s ruling, the Relentless plaintiffs’ attorneys said that the decision “will recalibrate the balance of power between agencies and courts” and “make it harder for those agencies to adopt regulatory programs that exceed the authority conferred on them by Congress.”

Some predicted chaos in the wake of the ruling.

“Overturning Chevron could invite legal challenges to any and all agency determinations of ambiguous statutes by any stakeholder, leaving individual courts with the impractical task of determining the ‘correct’ meaning of statutes without the benefit of requisite expertise, practical experience, or public engagement,” wrote Sahil Agrawal, MD, PhD, Joseph S. Ross, MD, and Reshma Ramachandran, MD, in JAMA in an opinion piece in March that considered the ramifications of overturning Chevron.

“The spillover effects for medicine and public health, in turn, will be consequential,” they wrote.

In an analysis published in April, the Kaiser Family Foundation noted many potential ramifications on patient and consumer protections in the health insurance market. For instance, courts could vacate current rules governing protections under the Affordable Care Act, including that health plans offer a range of free preventive health services, such as breast, cervical, colon, and lung cancer screening.
 

Congressional, White House Reaction

Many legal observers said the ruling will have the effect of requiring Congress to write ever-more dense and exacting legislation to prevent agencies from interpreting any gaps.

Some members of Congress welcomed the decision.

Senate Minority Leader Mitch McConnell (R-Kentucky) said in a statement, “The Constitution vests Congress with the sole authority to make law,” adding, “the Supreme Court made it clear today that our system of government leaves no room for an unelected bureaucracy to co-opt this authority for itself.”

In a post on X, Senate Majority Leader Chuck Schumer (D-New York) accused the Court of siding with “special interests and giant corporations.” Added Mr. Schumer, “Their headlong rush to overturn 40 years of precedent and impose their own radical views is appalling.”

White House Press Secretary Karine Jean-Pierre said in a statement that “While this decision undermines the ability of federal agencies to use their expertise as Congress intended to make government work for the people, the Biden-Harris Administration will not relent in our efforts to protect and serve every American.”

A version of this article first appeared on Medscape.com.

Experts say the US Supreme Court’s ruling Friday to overturn the decades-old “Chevron doctrine” could severely restrict the ability of federal agencies to regulate all aspects of healthcare.

Larry Levitt, executive vice president for health policy at the Kaiser Family Foundation, wrote on X, “my worry is that it will paralyze policymaking in healthcare and other areas,” because “Congress will try to fill in more details, making it harder to pass legislation.” He also wrote that federal agencies “will become very cautious in using their regulatory authority.”

In their 6-3 opinion reversing the “Chevron doctrine” — which has been followed since a 1984 Court opinion — the Justices said that the judiciary should no longer have to defer to federal agency interpretations of laws. Existing federal law “requires courts to exercise their independent judgment in deciding whether an agency has acted within its statutory authority,” said the Court, in stating why Chevron should be overruled.

Writing for the majority in the combined cases — Relentless v. Department of Commerce and Loper Bright Enterprises v. Raimondo — Chief Justice John Roberts Jr. wrote that “agencies have no special competence in resolving statutory ambiguities. Courts do.”

In a dissenting opinion, Justice Elena Kagan said the decision was a judicial power grab and would result in a “jolt to the legal system.” She was joined by Justices Sonia Sotomayor and Ketanji Brown Jackson.

The opinion will have many repercussions, said lawyer and Supreme Court watcher Amy Howe. The Chevron ruling has been “one of the most important rulings on federal administrative law, cited by federal courts more than 18,000 times,” she wrote on her blog.

For example, without the long-standing deference to agencies under Chevron, healthcare providers may have more opportunities to challenge how federal officials set Medicare reimbursement for hospital procedures or prescription drugs, Baker Donelson healthcare attorneys McKenna Cloud and Thomas Barnard wrote in an analysis.

Seventeen health organizations issued a joint statement signaling their disappointment. 

“We anticipate that today’s ruling will cause significant disruption to publicly funded health insurance programs, to the stability of this country’s healthcare and food and drug review systems, and to the health and well-being of the patients and consumers we serve,” wrote the organizations, which included American Academy of Pediatrics, American Cancer Society, American Cancer Society Cancer Action Network, ALS Association, American Heart Association, American Lung Association, American Public Health Association, American Thoracic Society, Bazelon Center for Mental Health Law, Campaign for Tobacco-Free Kids, Child Neurology Foundation, Epilepsy Foundation, Muscular Dystrophy Association, National Health Law Program, Physicians for Social Responsibility, The Leukemia & Lymphoma Society, and Truth Initiative.

“It’s much harder for agencies to exercise power without some power to interpret statues. This is big,” wrote Berkeley Law Professor Orin Kerr on X.
 

A New, Uncertain Landscape for Healthcare

In the original Chevron case, the Court ruled that federal agencies had relevant expertise and should be given deference in resolving ambiguities that Congress had not spelled out in legislation.

In Relentless and Loper Bright, the plaintiffs argued that federal agencies overstepped their authority by issuing a rule that required commercial fishing vessels to pay for professional observers to monitor their catch.

In a statement after Friday’s ruling, the Relentless plaintiffs’ attorneys said that the decision “will recalibrate the balance of power between agencies and courts” and “make it harder for those agencies to adopt regulatory programs that exceed the authority conferred on them by Congress.”

Some predicted chaos in the wake of the ruling.

“Overturning Chevron could invite legal challenges to any and all agency determinations of ambiguous statutes by any stakeholder, leaving individual courts with the impractical task of determining the ‘correct’ meaning of statutes without the benefit of requisite expertise, practical experience, or public engagement,” wrote Sahil Agrawal, MD, PhD, Joseph S. Ross, MD, and Reshma Ramachandran, MD, in JAMA in an opinion piece in March that considered the ramifications of overturning Chevron.

“The spillover effects for medicine and public health, in turn, will be consequential,” they wrote.

In an analysis published in April, the Kaiser Family Foundation noted many potential ramifications on patient and consumer protections in the health insurance market. For instance, courts could vacate current rules governing protections under the Affordable Care Act, including that health plans offer a range of free preventive health services, such as breast, cervical, colon, and lung cancer screening.
 

Congressional, White House Reaction

Many legal observers said the ruling will have the effect of requiring Congress to write ever-more dense and exacting legislation to prevent agencies from interpreting any gaps.

Some members of Congress welcomed the decision.

Senate Minority Leader Mitch McConnell (R-Kentucky) said in a statement, “The Constitution vests Congress with the sole authority to make law,” adding, “the Supreme Court made it clear today that our system of government leaves no room for an unelected bureaucracy to co-opt this authority for itself.”

In a post on X, Senate Majority Leader Chuck Schumer (D-New York) accused the Court of siding with “special interests and giant corporations.” Added Mr. Schumer, “Their headlong rush to overturn 40 years of precedent and impose their own radical views is appalling.”

White House Press Secretary Karine Jean-Pierre said in a statement that “While this decision undermines the ability of federal agencies to use their expertise as Congress intended to make government work for the people, the Biden-Harris Administration will not relent in our efforts to protect and serve every American.”

A version of this article first appeared on Medscape.com.