TOPLINE:

Women who received false-positive mammography results were less likely to return for future screenings.

METHODOLOGY:

• Researchers analyzed more than three million screening mammograms from more than one million women aged between 40 and 73 years at nearly 200 facilities in the Breast Cancer Surveillance Consortium between 2005 and 2017.
• Mammography results were classified as true negative or false positive; women who received false-positive results were either asked to come back for additional imaging, a short interval follow-up or biopsy recommendations.
• The primary outcome was the probability of returning for routine screening within 9-30 months after a false-positive or true-negative result, adjusted for race, ethnicity, age, and time since the last mammogram.
• Women with two screening mammograms within 5 years were also analyzed to evaluate the probability of returning for a third screening based on combinations of true-negative and false-positive results.

TAKEAWAY:

• Nearly 10.0% (95% CI, 9.1%-10.5%) of women who received screening mammograms got a false-positive result, 5.8% (95% CI, 5.5%-6.2%) of whom needed immediate additional imaging, 2.7% (95% CI, 2.3%-3.2%) needed short-interval follow-up, and 1.3% (95% CI, 1.1%-1.4%) were recommended for a biopsy.
• Women were more likely to return for screening after a true-negative result (76.9%) than after a false positive to obtain more data through additional imaging (72.4%), short-interval follow-ups (54.7%), or biopsy (61.0%).
• Asian and Hispanic/Latinx women who received a false-positive result were much less likely to return for a screening than women of the same groups who received a true-negative result, with recommendations for short interval follow-up (decrease of 20-25 percentage points) or biopsy (decrease of 13-14 percentage points).
• For women who had two screening mammograms within 5 years, receiving a false-positive result on the second was linked to a lower likelihood of returning for a third screening, regardless of results for the first.

IN PRACTICE:

“Physicians should educate their patients about the importance of continued screening after false-positive results, especially given the associated increased future risk for breast cancer,” study authors wrote.

SOURCE:

The study was led by Diana L. Miglioretti, PhD, of the Department of Public Health Sciences at the University of California, Davis, and published online on September 3 in Annals of Internal Medicine.

LIMITATIONS:

Women could receive care at facilities outside of the trial, which may have affected the accuracy of return rates. The study did not track a complete history of false-positive results. The study did not have information about how often physicians recommend screenings and did not account for other health conditions.

DISCLOSURES:

One coauthor reported receiving grants from the National Institutes of Health and the American Cancer Society, as well as consulting fees from the University of Florida, Gainesville.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Women who received false-positive mammography results were less likely to return for future screenings.

METHODOLOGY:

• Researchers analyzed more than three million screening mammograms from more than one million women aged between 40 and 73 years at nearly 200 facilities in the Breast Cancer Surveillance Consortium between 2005 and 2017.
• Mammography results were classified as true negative or false positive; women who received false-positive results were either asked to come back for additional imaging, a short interval follow-up or biopsy recommendations.
• The primary outcome was the probability of returning for routine screening within 9-30 months after a false-positive or true-negative result, adjusted for race, ethnicity, age, and time since the last mammogram.
• Women with two screening mammograms within 5 years were also analyzed to evaluate the probability of returning for a third screening based on combinations of true-negative and false-positive results.

TAKEAWAY:

• Nearly 10.0% (95% CI, 9.1%-10.5%) of women who received screening mammograms got a false-positive result, 5.8% (95% CI, 5.5%-6.2%) of whom needed immediate additional imaging, 2.7% (95% CI, 2.3%-3.2%) needed short-interval follow-up, and 1.3% (95% CI, 1.1%-1.4%) were recommended for a biopsy.
• Women were more likely to return for screening after a true-negative result (76.9%) than after a false positive to obtain more data through additional imaging (72.4%), short-interval follow-ups (54.7%), or biopsy (61.0%).
• Asian and Hispanic/Latinx women who received a false-positive result were much less likely to return for a screening than women of the same groups who received a true-negative result, with recommendations for short interval follow-up (decrease of 20-25 percentage points) or biopsy (decrease of 13-14 percentage points).
• For women who had two screening mammograms within 5 years, receiving a false-positive result on the second was linked to a lower likelihood of returning for a third screening, regardless of results for the first.

IN PRACTICE:

“Physicians should educate their patients about the importance of continued screening after false-positive results, especially given the associated increased future risk for breast cancer,” study authors wrote.

SOURCE:

The study was led by Diana L. Miglioretti, PhD, of the Department of Public Health Sciences at the University of California, Davis, and published online on September 3 in Annals of Internal Medicine.

LIMITATIONS:

Women could receive care at facilities outside of the trial, which may have affected the accuracy of return rates. The study did not track a complete history of false-positive results. The study did not have information about how often physicians recommend screenings and did not account for other health conditions.

DISCLOSURES:

One coauthor reported receiving grants from the National Institutes of Health and the American Cancer Society, as well as consulting fees from the University of Florida, Gainesville.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Women who received false-positive mammography results were less likely to return for future screenings.

METHODOLOGY:

• Researchers analyzed more than three million screening mammograms from more than one million women aged between 40 and 73 years at nearly 200 facilities in the Breast Cancer Surveillance Consortium between 2005 and 2017.
• Mammography results were classified as true negative or false positive; women who received false-positive results were either asked to come back for additional imaging, a short interval follow-up or biopsy recommendations.
• The primary outcome was the probability of returning for routine screening within 9-30 months after a false-positive or true-negative result, adjusted for race, ethnicity, age, and time since the last mammogram.
• Women with two screening mammograms within 5 years were also analyzed to evaluate the probability of returning for a third screening based on combinations of true-negative and false-positive results.

TAKEAWAY:

• Nearly 10.0% (95% CI, 9.1%-10.5%) of women who received screening mammograms got a false-positive result, 5.8% (95% CI, 5.5%-6.2%) of whom needed immediate additional imaging, 2.7% (95% CI, 2.3%-3.2%) needed short-interval follow-up, and 1.3% (95% CI, 1.1%-1.4%) were recommended for a biopsy.
• Women were more likely to return for screening after a true-negative result (76.9%) than after a false positive to obtain more data through additional imaging (72.4%), short-interval follow-ups (54.7%), or biopsy (61.0%).
• Asian and Hispanic/Latinx women who received a false-positive result were much less likely to return for a screening than women of the same groups who received a true-negative result, with recommendations for short interval follow-up (decrease of 20-25 percentage points) or biopsy (decrease of 13-14 percentage points).
• For women who had two screening mammograms within 5 years, receiving a false-positive result on the second was linked to a lower likelihood of returning for a third screening, regardless of results for the first.

IN PRACTICE:

“Physicians should educate their patients about the importance of continued screening after false-positive results, especially given the associated increased future risk for breast cancer,” study authors wrote.

SOURCE:

The study was led by Diana L. Miglioretti, PhD, of the Department of Public Health Sciences at the University of California, Davis, and published online on September 3 in Annals of Internal Medicine.

LIMITATIONS:

Women could receive care at facilities outside of the trial, which may have affected the accuracy of return rates. The study did not track a complete history of false-positive results. The study did not have information about how often physicians recommend screenings and did not account for other health conditions.

DISCLOSURES:

One coauthor reported receiving grants from the National Institutes of Health and the American Cancer Society, as well as consulting fees from the University of Florida, Gainesville.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

When it comes to selecting a cost-effective, first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

For survival, generic imatinib remains the gold standard, Elias Jabbour, MD, said during a session at the annual meeting of the Society of Hematologic Oncology in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but not yet available in the United States, so generic imatinib is the best current choice, said Dr. Jabbour, a professor of medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, Houston.

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40,000-$50,000 per quality-adjusted life-year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Dr. Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7-8 years is also needed.

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Dr. Jabbour and colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both frontline and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when a second-generation TKI was used first line. 

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued. 

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and eventually generic dasatinib and possibly other generic second-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patients over time.

Dr. Jabbour disclosed ties with AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda, and Terns.

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

When it comes to selecting a cost-effective, first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

For survival, generic imatinib remains the gold standard, Elias Jabbour, MD, said during a session at the annual meeting of the Society of Hematologic Oncology in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but not yet available in the United States, so generic imatinib is the best current choice, said Dr. Jabbour, a professor of medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, Houston.

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40,000-$50,000 per quality-adjusted life-year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Dr. Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7-8 years is also needed.

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Dr. Jabbour and colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both frontline and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when a second-generation TKI was used first line. 

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued. 

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and eventually generic dasatinib and possibly other generic second-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patients over time.

Dr. Jabbour disclosed ties with AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda, and Terns.

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

When it comes to selecting a cost-effective, first-line tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), consider the treatment goal.

For survival, generic imatinib remains the gold standard, Elias Jabbour, MD, said during a session at the annual meeting of the Society of Hematologic Oncology in Houston.

For treatment-free remission, generic dasatinib or another generic second-generation TKI is needed, but not yet available in the United States, so generic imatinib is the best current choice, said Dr. Jabbour, a professor of medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, Houston.

Prior to the availability of generic imatinib, that wasn’t the case, he noted, explaining that second-generation TKIs met the cost-efficacy criteria, but now — at about $35 per month or about $400 per year — imatinib is far less expensive than the approximately $250,000 per year that brand-name second- and third-generation TKIs can currently cost.

To have treatment value, any new TKI should cost $40,000-$50,000 per quality-adjusted life-year, which is defined as the quality and duration of life after a novel TKI vs with the existing standard of care, Dr. Jabbour said.

And to qualify as a frontline therapy for CML, any new TKI should show efficacy superior to second-generation TKIs, in addition to meeting the cost-effectiveness criteria.

“It is hard to show survival benefit anymore, but we need to improve on the rate of durable deep molecular remission,” he said.

An equivalent or better long-term safety profile over at least 7-8 years is also needed.

Based on the current literature, none of the TKIs currently being evaluated has met that standard, although some trials are ongoing.

In a recent editorial, Dr. Jabbour and colleagues outlined treatment recommendations based on the currently available data. They suggested using lower-than-approved doses of TKIs in both frontline and later therapies to reduce toxicity, improve treatment compliance, and reduce costs.

They also suggested that the absence of an early molecular response might not warrant changing the TKI, especially when a second-generation TKI was used first line. 

When treatment-free remission is not a therapeutic goal or is unlikely, changing the TKI to improve the depth of molecular response, which has been shown to improve the likelihood of treatment-free remission, could do more harm than good, they argued. 

Instead, consider reducing the dose to manage reversible side effects, they suggested, noting that generic imatinib, and eventually generic dasatinib and possibly other generic second-generation TKIs, will likely offer 90% of patients with CML an effective, safe, and affordable treatment that normalizes life expectancy and leads to treatment-free remission in 30%-50% of patients over time.

Dr. Jabbour disclosed ties with AbbVie, Almoosa Specialist Hospital, Amgen, Ascentage Pharma, Biologix FZ, Hikma Pharmaceuticals, Kite, Takeda, and Terns.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

This transcript has been edited for clarity. 

I’d like to talk about a very different topic from what I normally discuss, which is probably relatively rarely addressed in clinical conversations among clinicians. There was a very provocative commentary that appeared in JCO Oncology Practice, titled “Hollywood’s Take on Oncology: Portrayal of Cancer in Movies, 2010-2020.”

All of us, as we grow up — as kids, adolescents, young adults, adults, and older individuals — watch television and movies. The older of us know that the doctor in everybody’s home that we all wanted was Marcus Welby. Of course, there was Dr. Kildare, ER, Grey’s Anatomy, and St. Elsewhere. There was Love Story and Brian’s Song. We all know about these. 

This particular review was fascinating. The authors looked at 100 English-language movies that had cancer included in the storyline over the past decade. They asked some relatively simple questions: How did they discuss it? What were the tumor types they discussed? What were the outcomes? 

The question is, what is the public seeing? If you watch these movies and you don’t have family experience or personal experience with cancer, what do you think about cancer? Maybe this is what you know about it. Despite what the National Cancer Institute or the American Society of Clinical Oncology tells you, this may be what you know.

What they showed was really quite interesting. Only one third of the movies even said the cancer type, so in two thirds, you just knew they had “cancer.”

There is another very interesting phenomenon. What do you think was the most common cancer type when they did define the cancer? It was brain tumors, even though we know that brain tumors are certainly not even within the top 10. They’re obviously very serious cancers, but if you’re talking about common cancers, brain cancer doesn’t rank in the top 10, and it was the most common cancer on these shows.

The authors of this paper made the point of whether this would be an opportunity for filmmakers. Again, with the storyline, they’re trying to sell a product here, but wouldn’t this be the opportunity to provide some information about the reality of cancer? They could emphasize the fact that smokers get lung cancer. In my opinion, they could discuss cervical cancer and comment that if HPV vaccination had been done, maybe this would not have happened.

They noted that the majority of cancers in these movies were incurable, and they commented that that’s not the reality today. Today, obviously, many of our cancers that weren’t curable have become quite curable for a percentage of patients, in addition to which, obviously, with early detection, we have a very high cure rate. How about trying to get that message out, too, that we’ve actually had increasing success?

They commented that there was very rarely, if ever, a conversation about multidisciplinary care, that somehow there are multiple doctors with multiple specialties involved. They noted that this is potentially a very important message to give out. They commented that in 12 of these movies, the patient refused cancer care. Again, that happens, but it’s clearly a rare event today. Maybe this is not really a very accurate depiction of what’s going on.

They commented on the fact that, obviously, we’re going back through the past 10 years, so there were no patients who received immunotherapy or targeted therapy. Again, the goal here is not to sell oncology care but to be accurate, or more accurate, about the state of treatment to the extent you can.

They noted that, in fact, there was essentially very little, if any, comment on palliative care or hospice care. The final point they made is that there was very little conversation in these movies about what we now recognize as financial distress in many of our patients. That’s an unfortunate reality and perhaps that might come in the future.

Again, the point of this was not to tell Hollywood how to make their movies but to have the oncology community recognize that if their patients or the families of their patients are seeing these movies, they are not getting a very accurate picture of what is happening in the oncology world today and that some education may very well be required.

Maurie Markman is Professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California, and President of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed the following relevant financial relationships: income in an amount equal to or greater than $250 from: GlaxoSmithKline; AstraZeneca.

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

This transcript has been edited for clarity. 

I’d like to talk about a very different topic from what I normally discuss, which is probably relatively rarely addressed in clinical conversations among clinicians. There was a very provocative commentary that appeared in JCO Oncology Practice, titled “Hollywood’s Take on Oncology: Portrayal of Cancer in Movies, 2010-2020.”

All of us, as we grow up — as kids, adolescents, young adults, adults, and older individuals — watch television and movies. The older of us know that the doctor in everybody’s home that we all wanted was Marcus Welby. Of course, there was Dr. Kildare, ER, Grey’s Anatomy, and St. Elsewhere. There was Love Story and Brian’s Song. We all know about these. 

This particular review was fascinating. The authors looked at 100 English-language movies that had cancer included in the storyline over the past decade. They asked some relatively simple questions: How did they discuss it? What were the tumor types they discussed? What were the outcomes? 

The question is, what is the public seeing? If you watch these movies and you don’t have family experience or personal experience with cancer, what do you think about cancer? Maybe this is what you know about it. Despite what the National Cancer Institute or the American Society of Clinical Oncology tells you, this may be what you know.

What they showed was really quite interesting. Only one third of the movies even said the cancer type, so in two thirds, you just knew they had “cancer.”

There is another very interesting phenomenon. What do you think was the most common cancer type when they did define the cancer? It was brain tumors, even though we know that brain tumors are certainly not even within the top 10. They’re obviously very serious cancers, but if you’re talking about common cancers, brain cancer doesn’t rank in the top 10, and it was the most common cancer on these shows.

The authors of this paper made the point of whether this would be an opportunity for filmmakers. Again, with the storyline, they’re trying to sell a product here, but wouldn’t this be the opportunity to provide some information about the reality of cancer? They could emphasize the fact that smokers get lung cancer. In my opinion, they could discuss cervical cancer and comment that if HPV vaccination had been done, maybe this would not have happened.

They noted that the majority of cancers in these movies were incurable, and they commented that that’s not the reality today. Today, obviously, many of our cancers that weren’t curable have become quite curable for a percentage of patients, in addition to which, obviously, with early detection, we have a very high cure rate. How about trying to get that message out, too, that we’ve actually had increasing success?

They commented that there was very rarely, if ever, a conversation about multidisciplinary care, that somehow there are multiple doctors with multiple specialties involved. They noted that this is potentially a very important message to give out. They commented that in 12 of these movies, the patient refused cancer care. Again, that happens, but it’s clearly a rare event today. Maybe this is not really a very accurate depiction of what’s going on.

They commented on the fact that, obviously, we’re going back through the past 10 years, so there were no patients who received immunotherapy or targeted therapy. Again, the goal here is not to sell oncology care but to be accurate, or more accurate, about the state of treatment to the extent you can.

They noted that, in fact, there was essentially very little, if any, comment on palliative care or hospice care. The final point they made is that there was very little conversation in these movies about what we now recognize as financial distress in many of our patients. That’s an unfortunate reality and perhaps that might come in the future.

Again, the point of this was not to tell Hollywood how to make their movies but to have the oncology community recognize that if their patients or the families of their patients are seeing these movies, they are not getting a very accurate picture of what is happening in the oncology world today and that some education may very well be required.

Maurie Markman is Professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California, and President of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed the following relevant financial relationships: income in an amount equal to or greater than $250 from: GlaxoSmithKline; AstraZeneca.

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

This transcript has been edited for clarity. 

I’d like to talk about a very different topic from what I normally discuss, which is probably relatively rarely addressed in clinical conversations among clinicians. There was a very provocative commentary that appeared in JCO Oncology Practice, titled “Hollywood’s Take on Oncology: Portrayal of Cancer in Movies, 2010-2020.”

All of us, as we grow up — as kids, adolescents, young adults, adults, and older individuals — watch television and movies. The older of us know that the doctor in everybody’s home that we all wanted was Marcus Welby. Of course, there was Dr. Kildare, ER, Grey’s Anatomy, and St. Elsewhere. There was Love Story and Brian’s Song. We all know about these. 

This particular review was fascinating. The authors looked at 100 English-language movies that had cancer included in the storyline over the past decade. They asked some relatively simple questions: How did they discuss it? What were the tumor types they discussed? What were the outcomes? 

The question is, what is the public seeing? If you watch these movies and you don’t have family experience or personal experience with cancer, what do you think about cancer? Maybe this is what you know about it. Despite what the National Cancer Institute or the American Society of Clinical Oncology tells you, this may be what you know.

What they showed was really quite interesting. Only one third of the movies even said the cancer type, so in two thirds, you just knew they had “cancer.”

There is another very interesting phenomenon. What do you think was the most common cancer type when they did define the cancer? It was brain tumors, even though we know that brain tumors are certainly not even within the top 10. They’re obviously very serious cancers, but if you’re talking about common cancers, brain cancer doesn’t rank in the top 10, and it was the most common cancer on these shows.

The authors of this paper made the point of whether this would be an opportunity for filmmakers. Again, with the storyline, they’re trying to sell a product here, but wouldn’t this be the opportunity to provide some information about the reality of cancer? They could emphasize the fact that smokers get lung cancer. In my opinion, they could discuss cervical cancer and comment that if HPV vaccination had been done, maybe this would not have happened.

They noted that the majority of cancers in these movies were incurable, and they commented that that’s not the reality today. Today, obviously, many of our cancers that weren’t curable have become quite curable for a percentage of patients, in addition to which, obviously, with early detection, we have a very high cure rate. How about trying to get that message out, too, that we’ve actually had increasing success?

They commented that there was very rarely, if ever, a conversation about multidisciplinary care, that somehow there are multiple doctors with multiple specialties involved. They noted that this is potentially a very important message to give out. They commented that in 12 of these movies, the patient refused cancer care. Again, that happens, but it’s clearly a rare event today. Maybe this is not really a very accurate depiction of what’s going on.

They commented on the fact that, obviously, we’re going back through the past 10 years, so there were no patients who received immunotherapy or targeted therapy. Again, the goal here is not to sell oncology care but to be accurate, or more accurate, about the state of treatment to the extent you can.

They noted that, in fact, there was essentially very little, if any, comment on palliative care or hospice care. The final point they made is that there was very little conversation in these movies about what we now recognize as financial distress in many of our patients. That’s an unfortunate reality and perhaps that might come in the future.

Again, the point of this was not to tell Hollywood how to make their movies but to have the oncology community recognize that if their patients or the families of their patients are seeing these movies, they are not getting a very accurate picture of what is happening in the oncology world today and that some education may very well be required.

Maurie Markman is Professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California, and President of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed the following relevant financial relationships: income in an amount equal to or greater than $250 from: GlaxoSmithKline; AstraZeneca.

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

This transcript has been edited for clarity.

Tricia Ward: I’m joined today by Dr. Scott R. Garrison, MD, PhD. He is a professor in the Department of Family Medicine at the University of Alberta in Edmonton, Alberta, Canada, and director of the Pragmatic Trials Collaborative.

You presented two studies at ESC. One is the BedMed study, comparing day vs nighttime dosing of blood pressure therapy. Can you tell us the top-line findings? 
 

BedMed and BedMed-Frail

Dr. Garrison: We were looking to validate an earlier study that suggested a large benefit of taking blood pressure medication at bedtime, as far as reducing major adverse cardiovascular events (MACEs). That was the MAPEC study. They suggested a 60% reduction. The BedMed trial was in hypertensive primary care patients in five Canadian provinces. We randomized well over 3000 patients to bedtime or morning medications. We looked at MACEs — so all-cause death or hospitalizations for acute coronary syndrome, stroke, or heart failure, and a bunch of safety outcomes.

Essentially, we found that it made absolutely no difference whatever time of day you took it in terms of MACEs and it didn’t make any difference to the adverse effects. It was safe to take it at bedtime. But it did not convey any extra cardiovascular benefit.

Ms. Ward: And then you did a second study, called BedMed-Frail. Do you want to tell us the reason you did that?

Dr. Garrison: BedMed-Frail took place in a nursing home population. We believed that it was possible that frail, older adults might have very different risks and benefits, and that they would probably be underrepresented, as they normally are in the main trial. 

We thought that because bedtime blood pressure medications would be theoretically preferentially lowering night pressure, which is already the lowest pressure of the day, that if you were at risk for hypotensive or ischemic adverse events, that might make it worse. We looked at falls and fractures; worsening cognition in case they had vascular dementia; and whether they developed decubitus ulcers (pressure sores) because you need a certain amount of pressure to get past any obstruction — in this case, it’s the weight of your body if you’re lying in bed all the time. 

We also looked at problem behaviors. People who have dementia have what’s called “sundowning,” where agitation and confusion are worse as the evening is going on. We looked at that on the off chance that it had anything to do with blood pressures being lower. And the BedMed-Frail results mirror those of BedMed exactly. So there was no cardiovascular benefit, and in this population, that was largely driven by mortality; one third of these people died every year. 

Ms. Ward: The median age was about 88?

Dr. Garrison: Yes, the median age was 88. There was no cardiovascular mortality advantage to bedtime dosing, but neither was there any signal of safety concerns. 
 

Other Complementary and Conflicting Studies

Ms. Ward: These two studies mirror the TIME study from the United Kingdom.

Dr. Garrison: Yes. We found exactly what TIME found. Our point estimate was pretty much the same. The hazard ratio in the main trial was 0.96. Theirs, I believe, was 0.95. Our findings agree completely with those of TIME and differ substantially from the previous trials that suggested a large benefit.

Ms. Ward: Those previous trials were MAPEC and the Hygia Chronotherapy Trial.

Dr. Garrison: MAPEC was the first one. While we were doing our trial, and while the TIME investigators were doing their trial, both of us trying to validate MAPEC, the same group published another study called Hygia, which also reported a large reduction: a 45% reduction in MACE with bedtime dosing.

Ms. Ward: You didn’t present it, but there was also a meta-analysis presented here by somebody independent.

Dr. Garrison: Yes, Ricky Turgeon. I know Ricky. We gave him patient-level data for his meta-analysis, but I was not otherwise involved. 

Ms. Ward: And the conclusion is the same.

Dr. Garrison: It’s the same. He only found the same five trials: MAPEC, Hygia, TIME, BedMed, and BedMed-Frail. Combining them all together, the CIs still span 1.0, so it didn’t end up being significant. But he also analyzed TIME and the BedMed trials separately — again suggesting that those trials showed no benefit.

Ms. Ward: There was a TIME substudy of night owls vs early risers or morning people, and there was a hint (or whatever you should say for a subanalysis of a neutral trial) that timing might make a difference there.

Dr. Garrison: They recently published, I guess it is a substudy, where they looked at people’s chronotype according to whether you consider yourself an early bird or a night owl. Their assessment was more detailed. They reported that if people were tending toward being early birds and they took their blood pressure medicine in the morning, or if they were night owls and they took it in the evening, that they tended to have statistically significantly better outcomes than the opposite timing. In that analysis, they were only looking at nonfatal myocardial infarction and nonfatal stroke. 

We did ask something that was related. We asked people: “Do we consider yourself more of an early bird or a night owl?” So we do have those data. For what I presented at ESC, we just looked at the primary outcome; we did subgroups according to early bird, night owl, and neither, and that was not statistically significant. It didn’t rule it out. There were some trends in the direction that the TIME group were suggesting. We do intend to do a closer look at that. 

But, you know, they call these “late-breaking trials,” and it really was in our case. We didn’t get the last of our data from the last province until the end of June, so we still are finishing up the analysis of the chronotype portion — so more to come in another month or so.
 

Do What You Like, or Stick to Morning Dosing?

Ms. Ward: For the purposes of people’s take-home message, does this mostly apply to once-daily–dosed antihypertensives?

Dr. Garrison: It was essentially once-daily medicines that were changed. The docs did have the opportunity to consolidate twice-daily meds into once-daily or switch to a different medication. That’s probably the area where adherence was the biggest issue, because it’s largely beta-blockers that were given twice daily at baseline, and they were less likely to want to change. 

At 6 months, 83% of once-daily medications were taken per allocation in the bedtime group and 95% per allocation in the morning group, which was actually pretty good. For angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium-channel blockers, the adherence was excellent. Again, it was beta-blockers taken twice a day where it fell down, and then also diuretics. But if you combine all diuretic medications (ie, pure diuretics and combo agents), still, 75% of them were successful at taking them at bedtime. Only 15% of people switching a diuretic to bedtime dosing actually had problems with nocturia. Most physicians think that they can’t get their patients to take those meds at bedtime, but you can. There’s probably no reason to take it at bedtime, but most people do tolerate it.

Ms. Ward: Is your advice to take it whenever you feel like? I know when TIME came out, Professor George Stergiou, who’s the incoming president of the International Society of Hypertension, said, well, maybe we should stick with the morning, because that’s what most of the trials did. 

Dr. Garrison: I think that›s a perfectly valid point of view, and maybe for a lot of people, that could be the default. There are some people, though, who will have a particular reason why one time is better. For instance, most people have no problems with calcium-channel blockers, but some get ankle swelling and you’re more likely to have that happen if you take them in the morning. Or lots of people want to take all their pills at the same time; blood pressure pills are easy ones to switch the timing of if you’re trying to accomplish that, and if that will help adherence. Basically, whatever time of day you can remember to take it the best is probably the right time.

Ms. Ward: Given where we are today, with your trials and TIME, do you think this is now settled science that it doesn’t make a difference?

Dr. Garrison: I’m probably the wrong person to ask, because I clearly have a bias. I think the methods in the TIME trial are really transparent and solid. I hope that when our papers come out, people will feel the same. You just have to look at the different trials. You need people like Dr. Stergiou to wade through the trials to help you with that.

Ms. Ward: Thank you very much for joining me today and discussing this trial.

Scott R. Garrison, MD, PhD, is Professor, Department of Family Medicine, University of Alberta in Edmonton, Alberta, Canada, and Staff Physician, Department of Family Medicine, Kaye Edmonton Clinic, and he has disclosed receiving research grants from Alberta Innovates (the Alberta Provincial Government) and the Canadian Institutes of Health Research (the Canadian Federal Government).

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

This transcript has been edited for clarity.

Tricia Ward: I’m joined today by Dr. Scott R. Garrison, MD, PhD. He is a professor in the Department of Family Medicine at the University of Alberta in Edmonton, Alberta, Canada, and director of the Pragmatic Trials Collaborative.

You presented two studies at ESC. One is the BedMed study, comparing day vs nighttime dosing of blood pressure therapy. Can you tell us the top-line findings? 
 

BedMed and BedMed-Frail

Dr. Garrison: We were looking to validate an earlier study that suggested a large benefit of taking blood pressure medication at bedtime, as far as reducing major adverse cardiovascular events (MACEs). That was the MAPEC study. They suggested a 60% reduction. The BedMed trial was in hypertensive primary care patients in five Canadian provinces. We randomized well over 3000 patients to bedtime or morning medications. We looked at MACEs — so all-cause death or hospitalizations for acute coronary syndrome, stroke, or heart failure, and a bunch of safety outcomes.

Essentially, we found that it made absolutely no difference whatever time of day you took it in terms of MACEs and it didn’t make any difference to the adverse effects. It was safe to take it at bedtime. But it did not convey any extra cardiovascular benefit.

Ms. Ward: And then you did a second study, called BedMed-Frail. Do you want to tell us the reason you did that?

Dr. Garrison: BedMed-Frail took place in a nursing home population. We believed that it was possible that frail, older adults might have very different risks and benefits, and that they would probably be underrepresented, as they normally are in the main trial. 

We thought that because bedtime blood pressure medications would be theoretically preferentially lowering night pressure, which is already the lowest pressure of the day, that if you were at risk for hypotensive or ischemic adverse events, that might make it worse. We looked at falls and fractures; worsening cognition in case they had vascular dementia; and whether they developed decubitus ulcers (pressure sores) because you need a certain amount of pressure to get past any obstruction — in this case, it’s the weight of your body if you’re lying in bed all the time. 

We also looked at problem behaviors. People who have dementia have what’s called “sundowning,” where agitation and confusion are worse as the evening is going on. We looked at that on the off chance that it had anything to do with blood pressures being lower. And the BedMed-Frail results mirror those of BedMed exactly. So there was no cardiovascular benefit, and in this population, that was largely driven by mortality; one third of these people died every year. 

Ms. Ward: The median age was about 88?

Dr. Garrison: Yes, the median age was 88. There was no cardiovascular mortality advantage to bedtime dosing, but neither was there any signal of safety concerns. 
 

Other Complementary and Conflicting Studies

Ms. Ward: These two studies mirror the TIME study from the United Kingdom.

Dr. Garrison: Yes. We found exactly what TIME found. Our point estimate was pretty much the same. The hazard ratio in the main trial was 0.96. Theirs, I believe, was 0.95. Our findings agree completely with those of TIME and differ substantially from the previous trials that suggested a large benefit.

Ms. Ward: Those previous trials were MAPEC and the Hygia Chronotherapy Trial.

Dr. Garrison: MAPEC was the first one. While we were doing our trial, and while the TIME investigators were doing their trial, both of us trying to validate MAPEC, the same group published another study called Hygia, which also reported a large reduction: a 45% reduction in MACE with bedtime dosing.

Ms. Ward: You didn’t present it, but there was also a meta-analysis presented here by somebody independent.

Dr. Garrison: Yes, Ricky Turgeon. I know Ricky. We gave him patient-level data for his meta-analysis, but I was not otherwise involved. 

Ms. Ward: And the conclusion is the same.

Dr. Garrison: It’s the same. He only found the same five trials: MAPEC, Hygia, TIME, BedMed, and BedMed-Frail. Combining them all together, the CIs still span 1.0, so it didn’t end up being significant. But he also analyzed TIME and the BedMed trials separately — again suggesting that those trials showed no benefit.

Ms. Ward: There was a TIME substudy of night owls vs early risers or morning people, and there was a hint (or whatever you should say for a subanalysis of a neutral trial) that timing might make a difference there.

Dr. Garrison: They recently published, I guess it is a substudy, where they looked at people’s chronotype according to whether you consider yourself an early bird or a night owl. Their assessment was more detailed. They reported that if people were tending toward being early birds and they took their blood pressure medicine in the morning, or if they were night owls and they took it in the evening, that they tended to have statistically significantly better outcomes than the opposite timing. In that analysis, they were only looking at nonfatal myocardial infarction and nonfatal stroke. 

We did ask something that was related. We asked people: “Do we consider yourself more of an early bird or a night owl?” So we do have those data. For what I presented at ESC, we just looked at the primary outcome; we did subgroups according to early bird, night owl, and neither, and that was not statistically significant. It didn’t rule it out. There were some trends in the direction that the TIME group were suggesting. We do intend to do a closer look at that. 

But, you know, they call these “late-breaking trials,” and it really was in our case. We didn’t get the last of our data from the last province until the end of June, so we still are finishing up the analysis of the chronotype portion — so more to come in another month or so.
 

Do What You Like, or Stick to Morning Dosing?

Ms. Ward: For the purposes of people’s take-home message, does this mostly apply to once-daily–dosed antihypertensives?

Dr. Garrison: It was essentially once-daily medicines that were changed. The docs did have the opportunity to consolidate twice-daily meds into once-daily or switch to a different medication. That’s probably the area where adherence was the biggest issue, because it’s largely beta-blockers that were given twice daily at baseline, and they were less likely to want to change. 

At 6 months, 83% of once-daily medications were taken per allocation in the bedtime group and 95% per allocation in the morning group, which was actually pretty good. For angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium-channel blockers, the adherence was excellent. Again, it was beta-blockers taken twice a day where it fell down, and then also diuretics. But if you combine all diuretic medications (ie, pure diuretics and combo agents), still, 75% of them were successful at taking them at bedtime. Only 15% of people switching a diuretic to bedtime dosing actually had problems with nocturia. Most physicians think that they can’t get their patients to take those meds at bedtime, but you can. There’s probably no reason to take it at bedtime, but most people do tolerate it.

Ms. Ward: Is your advice to take it whenever you feel like? I know when TIME came out, Professor George Stergiou, who’s the incoming president of the International Society of Hypertension, said, well, maybe we should stick with the morning, because that’s what most of the trials did. 

Dr. Garrison: I think that›s a perfectly valid point of view, and maybe for a lot of people, that could be the default. There are some people, though, who will have a particular reason why one time is better. For instance, most people have no problems with calcium-channel blockers, but some get ankle swelling and you’re more likely to have that happen if you take them in the morning. Or lots of people want to take all their pills at the same time; blood pressure pills are easy ones to switch the timing of if you’re trying to accomplish that, and if that will help adherence. Basically, whatever time of day you can remember to take it the best is probably the right time.

Ms. Ward: Given where we are today, with your trials and TIME, do you think this is now settled science that it doesn’t make a difference?

Dr. Garrison: I’m probably the wrong person to ask, because I clearly have a bias. I think the methods in the TIME trial are really transparent and solid. I hope that when our papers come out, people will feel the same. You just have to look at the different trials. You need people like Dr. Stergiou to wade through the trials to help you with that.

Ms. Ward: Thank you very much for joining me today and discussing this trial.

Scott R. Garrison, MD, PhD, is Professor, Department of Family Medicine, University of Alberta in Edmonton, Alberta, Canada, and Staff Physician, Department of Family Medicine, Kaye Edmonton Clinic, and he has disclosed receiving research grants from Alberta Innovates (the Alberta Provincial Government) and the Canadian Institutes of Health Research (the Canadian Federal Government).

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

This transcript has been edited for clarity.

Tricia Ward: I’m joined today by Dr. Scott R. Garrison, MD, PhD. He is a professor in the Department of Family Medicine at the University of Alberta in Edmonton, Alberta, Canada, and director of the Pragmatic Trials Collaborative.

You presented two studies at ESC. One is the BedMed study, comparing day vs nighttime dosing of blood pressure therapy. Can you tell us the top-line findings? 
 

BedMed and BedMed-Frail

Dr. Garrison: We were looking to validate an earlier study that suggested a large benefit of taking blood pressure medication at bedtime, as far as reducing major adverse cardiovascular events (MACEs). That was the MAPEC study. They suggested a 60% reduction. The BedMed trial was in hypertensive primary care patients in five Canadian provinces. We randomized well over 3000 patients to bedtime or morning medications. We looked at MACEs — so all-cause death or hospitalizations for acute coronary syndrome, stroke, or heart failure, and a bunch of safety outcomes.

Essentially, we found that it made absolutely no difference whatever time of day you took it in terms of MACEs and it didn’t make any difference to the adverse effects. It was safe to take it at bedtime. But it did not convey any extra cardiovascular benefit.

Ms. Ward: And then you did a second study, called BedMed-Frail. Do you want to tell us the reason you did that?

Dr. Garrison: BedMed-Frail took place in a nursing home population. We believed that it was possible that frail, older adults might have very different risks and benefits, and that they would probably be underrepresented, as they normally are in the main trial. 

We thought that because bedtime blood pressure medications would be theoretically preferentially lowering night pressure, which is already the lowest pressure of the day, that if you were at risk for hypotensive or ischemic adverse events, that might make it worse. We looked at falls and fractures; worsening cognition in case they had vascular dementia; and whether they developed decubitus ulcers (pressure sores) because you need a certain amount of pressure to get past any obstruction — in this case, it’s the weight of your body if you’re lying in bed all the time. 

We also looked at problem behaviors. People who have dementia have what’s called “sundowning,” where agitation and confusion are worse as the evening is going on. We looked at that on the off chance that it had anything to do with blood pressures being lower. And the BedMed-Frail results mirror those of BedMed exactly. So there was no cardiovascular benefit, and in this population, that was largely driven by mortality; one third of these people died every year. 

Ms. Ward: The median age was about 88?

Dr. Garrison: Yes, the median age was 88. There was no cardiovascular mortality advantage to bedtime dosing, but neither was there any signal of safety concerns. 
 

Other Complementary and Conflicting Studies

Ms. Ward: These two studies mirror the TIME study from the United Kingdom.

Dr. Garrison: Yes. We found exactly what TIME found. Our point estimate was pretty much the same. The hazard ratio in the main trial was 0.96. Theirs, I believe, was 0.95. Our findings agree completely with those of TIME and differ substantially from the previous trials that suggested a large benefit.

Ms. Ward: Those previous trials were MAPEC and the Hygia Chronotherapy Trial.

Dr. Garrison: MAPEC was the first one. While we were doing our trial, and while the TIME investigators were doing their trial, both of us trying to validate MAPEC, the same group published another study called Hygia, which also reported a large reduction: a 45% reduction in MACE with bedtime dosing.

Ms. Ward: You didn’t present it, but there was also a meta-analysis presented here by somebody independent.

Dr. Garrison: Yes, Ricky Turgeon. I know Ricky. We gave him patient-level data for his meta-analysis, but I was not otherwise involved. 

Ms. Ward: And the conclusion is the same.

Dr. Garrison: It’s the same. He only found the same five trials: MAPEC, Hygia, TIME, BedMed, and BedMed-Frail. Combining them all together, the CIs still span 1.0, so it didn’t end up being significant. But he also analyzed TIME and the BedMed trials separately — again suggesting that those trials showed no benefit.

Ms. Ward: There was a TIME substudy of night owls vs early risers or morning people, and there was a hint (or whatever you should say for a subanalysis of a neutral trial) that timing might make a difference there.

Dr. Garrison: They recently published, I guess it is a substudy, where they looked at people’s chronotype according to whether you consider yourself an early bird or a night owl. Their assessment was more detailed. They reported that if people were tending toward being early birds and they took their blood pressure medicine in the morning, or if they were night owls and they took it in the evening, that they tended to have statistically significantly better outcomes than the opposite timing. In that analysis, they were only looking at nonfatal myocardial infarction and nonfatal stroke. 

We did ask something that was related. We asked people: “Do we consider yourself more of an early bird or a night owl?” So we do have those data. For what I presented at ESC, we just looked at the primary outcome; we did subgroups according to early bird, night owl, and neither, and that was not statistically significant. It didn’t rule it out. There were some trends in the direction that the TIME group were suggesting. We do intend to do a closer look at that. 

But, you know, they call these “late-breaking trials,” and it really was in our case. We didn’t get the last of our data from the last province until the end of June, so we still are finishing up the analysis of the chronotype portion — so more to come in another month or so.
 

Do What You Like, or Stick to Morning Dosing?

Ms. Ward: For the purposes of people’s take-home message, does this mostly apply to once-daily–dosed antihypertensives?

Dr. Garrison: It was essentially once-daily medicines that were changed. The docs did have the opportunity to consolidate twice-daily meds into once-daily or switch to a different medication. That’s probably the area where adherence was the biggest issue, because it’s largely beta-blockers that were given twice daily at baseline, and they were less likely to want to change. 

At 6 months, 83% of once-daily medications were taken per allocation in the bedtime group and 95% per allocation in the morning group, which was actually pretty good. For angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium-channel blockers, the adherence was excellent. Again, it was beta-blockers taken twice a day where it fell down, and then also diuretics. But if you combine all diuretic medications (ie, pure diuretics and combo agents), still, 75% of them were successful at taking them at bedtime. Only 15% of people switching a diuretic to bedtime dosing actually had problems with nocturia. Most physicians think that they can’t get their patients to take those meds at bedtime, but you can. There’s probably no reason to take it at bedtime, but most people do tolerate it.

Ms. Ward: Is your advice to take it whenever you feel like? I know when TIME came out, Professor George Stergiou, who’s the incoming president of the International Society of Hypertension, said, well, maybe we should stick with the morning, because that’s what most of the trials did. 

Dr. Garrison: I think that›s a perfectly valid point of view, and maybe for a lot of people, that could be the default. There are some people, though, who will have a particular reason why one time is better. For instance, most people have no problems with calcium-channel blockers, but some get ankle swelling and you’re more likely to have that happen if you take them in the morning. Or lots of people want to take all their pills at the same time; blood pressure pills are easy ones to switch the timing of if you’re trying to accomplish that, and if that will help adherence. Basically, whatever time of day you can remember to take it the best is probably the right time.

Ms. Ward: Given where we are today, with your trials and TIME, do you think this is now settled science that it doesn’t make a difference?

Dr. Garrison: I’m probably the wrong person to ask, because I clearly have a bias. I think the methods in the TIME trial are really transparent and solid. I hope that when our papers come out, people will feel the same. You just have to look at the different trials. You need people like Dr. Stergiou to wade through the trials to help you with that.

Ms. Ward: Thank you very much for joining me today and discussing this trial.

Scott R. Garrison, MD, PhD, is Professor, Department of Family Medicine, University of Alberta in Edmonton, Alberta, Canada, and Staff Physician, Department of Family Medicine, Kaye Edmonton Clinic, and he has disclosed receiving research grants from Alberta Innovates (the Alberta Provincial Government) and the Canadian Institutes of Health Research (the Canadian Federal Government).

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

Hematologists and rheumatologists may be able to adopt a more aggressive approach for managing low-grade marginal lymphoma in Sjögren disease, particularly mucosa-associated lymphoid tissue (MALT) lymphoma, based on recent findings that confirmed a key early biomarker and found that a systemic treatment strategy reduced Sjögren disease activity and the risk for lymphoma relapse.

Two European studies published in The Lancet Rheumatology — one a case-control study reporting that rheumatoid factor (RF) was an early and strong predictor of Sjögren disease–related MALT lymphoma and the other a retrospective study that found a combination of chemotherapy and anti-CD20 therapy with rituximab as a first-line treatment for lymphoma was more effective than localized treatment or watch-and-wait approach in minimizing autoimmune activity and treating the lymphoma — potentially shed new light on strategies to manage Sjögren disease–related lymphoma.

A commentary accompanying the studies noted that 5%-10% of patients with Sjögren disease will develop non-Hodgkin B-cell lymphoma, with marginal lymphoma the most common type of low-grade lymphoma. The commentary, led by Suzanne Arends, MD, a rheumatologist at the University of Groningen in Groningen, the Netherlands, found the studies “clinically relevant” but stated that the lack of consistent definitions between the two studies along with their retrospective nature prevent any “definitive conclusions.”
 

High Lymphoma Risk in Sjögren Disease

“It is the autoimmune disease in which the risk of lymphoma is the highest, a 10- to 20-fold increase of the risk of lymphoma in this disease,” Xavier Mariette, MD, PhD, co-senior author of the retrospective treatment study, said of Sjögren disease.

These lymphomas are predominantly the marginal zone type, specifically MALT occurring in the salivary glands, the same site of the autoimmune disease, said Dr. Mariette, who is the head of Rheumatology and professor at Université Paris-Saclay and Hôpital Bicêtre. Autoimmune B cells become lymphomatous. “So there is a continuity between autoimmunity and lymphoma genesis,” Dr. Mariette told this news organization. Typically, hematologists do not treat the lymphoma if it doesn’t migrate beyond the salivary glands, he said.

RF Biomarker

The case-control study by researchers in Italy and Greece included 80 patients with Sjögren-related MALT lymphoma matched to controls with Sjögren disease who did not have lymphoma.

“We showed that rheumatoid factor positivity at the time of Sjögren’s disease diagnosis serves as the most reliable and temporally distant independent predictor of MALT lymphoma development,” lead author Andreas Goules, MD, a pathophysiologist at the National and Kapodistrian University of Athens, Athens, Greece, told this news organization.

What Future Studies Should Look At

The studies call for further research into biomarkers for Sjögren disease–related lymphoma and treatment of the disease, both Dr. Mariette and Dr. Goules said.

Dr. Goules said a multicenter prospective study is needed to measure RF positivity and RF titers over time and determine whether higher levels mean an increased risk for lymphoma development or a shorter time interval until lymphoma onset. “Such a study requires a large number of RF-positive Sjögren’s disease patients who would be followed up for a long period of time,” Dr. Goules said.

To further evaluate treatment approaches for Sjögren disease–related lymphoma, Dr. Mariette said, a prospective study should compare the watch-and-wait approach with combination chemotherapy and anti-CD20 therapy. “It would be difficult to run because the primary endpoint would be lymphoma progression–free survival, and the secondary would be Sjögren’s relapse and mortality, but it would take a lot of time,” he said.

He added, “It’s a reason why this retrospective study is important. Maybe if we had another retrospective study reaching the same conclusion, I think it would be very, very strong evidence.”

Funding for the case-control study came from the European Commission–Horizon 2020 program. The retrospective treatment study had no outside funding. Dr. Mariette disclosed financial relationships with AstraZeneca, Bristol-Myers Squibb, Galapagos, GlaxoSmithKline, Novartis, and Pfizer. Dr. Alderuccio, Dr. Goules, and Dr. Baer had no relevant relationships to disclose.

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

Hematologists and rheumatologists may be able to adopt a more aggressive approach for managing low-grade marginal lymphoma in Sjögren disease, particularly mucosa-associated lymphoid tissue (MALT) lymphoma, based on recent findings that confirmed a key early biomarker and found that a systemic treatment strategy reduced Sjögren disease activity and the risk for lymphoma relapse.

Two European studies published in The Lancet Rheumatology — one a case-control study reporting that rheumatoid factor (RF) was an early and strong predictor of Sjögren disease–related MALT lymphoma and the other a retrospective study that found a combination of chemotherapy and anti-CD20 therapy with rituximab as a first-line treatment for lymphoma was more effective than localized treatment or watch-and-wait approach in minimizing autoimmune activity and treating the lymphoma — potentially shed new light on strategies to manage Sjögren disease–related lymphoma.

A commentary accompanying the studies noted that 5%-10% of patients with Sjögren disease will develop non-Hodgkin B-cell lymphoma, with marginal lymphoma the most common type of low-grade lymphoma. The commentary, led by Suzanne Arends, MD, a rheumatologist at the University of Groningen in Groningen, the Netherlands, found the studies “clinically relevant” but stated that the lack of consistent definitions between the two studies along with their retrospective nature prevent any “definitive conclusions.”
 

High Lymphoma Risk in Sjögren Disease

“It is the autoimmune disease in which the risk of lymphoma is the highest, a 10- to 20-fold increase of the risk of lymphoma in this disease,” Xavier Mariette, MD, PhD, co-senior author of the retrospective treatment study, said of Sjögren disease.

These lymphomas are predominantly the marginal zone type, specifically MALT occurring in the salivary glands, the same site of the autoimmune disease, said Dr. Mariette, who is the head of Rheumatology and professor at Université Paris-Saclay and Hôpital Bicêtre. Autoimmune B cells become lymphomatous. “So there is a continuity between autoimmunity and lymphoma genesis,” Dr. Mariette told this news organization. Typically, hematologists do not treat the lymphoma if it doesn’t migrate beyond the salivary glands, he said.

RF Biomarker

The case-control study by researchers in Italy and Greece included 80 patients with Sjögren-related MALT lymphoma matched to controls with Sjögren disease who did not have lymphoma.

“We showed that rheumatoid factor positivity at the time of Sjögren’s disease diagnosis serves as the most reliable and temporally distant independent predictor of MALT lymphoma development,” lead author Andreas Goules, MD, a pathophysiologist at the National and Kapodistrian University of Athens, Athens, Greece, told this news organization.

What Future Studies Should Look At

The studies call for further research into biomarkers for Sjögren disease–related lymphoma and treatment of the disease, both Dr. Mariette and Dr. Goules said.

Dr. Goules said a multicenter prospective study is needed to measure RF positivity and RF titers over time and determine whether higher levels mean an increased risk for lymphoma development or a shorter time interval until lymphoma onset. “Such a study requires a large number of RF-positive Sjögren’s disease patients who would be followed up for a long period of time,” Dr. Goules said.

To further evaluate treatment approaches for Sjögren disease–related lymphoma, Dr. Mariette said, a prospective study should compare the watch-and-wait approach with combination chemotherapy and anti-CD20 therapy. “It would be difficult to run because the primary endpoint would be lymphoma progression–free survival, and the secondary would be Sjögren’s relapse and mortality, but it would take a lot of time,” he said.

He added, “It’s a reason why this retrospective study is important. Maybe if we had another retrospective study reaching the same conclusion, I think it would be very, very strong evidence.”

Funding for the case-control study came from the European Commission–Horizon 2020 program. The retrospective treatment study had no outside funding. Dr. Mariette disclosed financial relationships with AstraZeneca, Bristol-Myers Squibb, Galapagos, GlaxoSmithKline, Novartis, and Pfizer. Dr. Alderuccio, Dr. Goules, and Dr. Baer had no relevant relationships to disclose.

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

Hematologists and rheumatologists may be able to adopt a more aggressive approach for managing low-grade marginal lymphoma in Sjögren disease, particularly mucosa-associated lymphoid tissue (MALT) lymphoma, based on recent findings that confirmed a key early biomarker and found that a systemic treatment strategy reduced Sjögren disease activity and the risk for lymphoma relapse.

Two European studies published in The Lancet Rheumatology — one a case-control study reporting that rheumatoid factor (RF) was an early and strong predictor of Sjögren disease–related MALT lymphoma and the other a retrospective study that found a combination of chemotherapy and anti-CD20 therapy with rituximab as a first-line treatment for lymphoma was more effective than localized treatment or watch-and-wait approach in minimizing autoimmune activity and treating the lymphoma — potentially shed new light on strategies to manage Sjögren disease–related lymphoma.

A commentary accompanying the studies noted that 5%-10% of patients with Sjögren disease will develop non-Hodgkin B-cell lymphoma, with marginal lymphoma the most common type of low-grade lymphoma. The commentary, led by Suzanne Arends, MD, a rheumatologist at the University of Groningen in Groningen, the Netherlands, found the studies “clinically relevant” but stated that the lack of consistent definitions between the two studies along with their retrospective nature prevent any “definitive conclusions.”
 

High Lymphoma Risk in Sjögren Disease

“It is the autoimmune disease in which the risk of lymphoma is the highest, a 10- to 20-fold increase of the risk of lymphoma in this disease,” Xavier Mariette, MD, PhD, co-senior author of the retrospective treatment study, said of Sjögren disease.

These lymphomas are predominantly the marginal zone type, specifically MALT occurring in the salivary glands, the same site of the autoimmune disease, said Dr. Mariette, who is the head of Rheumatology and professor at Université Paris-Saclay and Hôpital Bicêtre. Autoimmune B cells become lymphomatous. “So there is a continuity between autoimmunity and lymphoma genesis,” Dr. Mariette told this news organization. Typically, hematologists do not treat the lymphoma if it doesn’t migrate beyond the salivary glands, he said.

RF Biomarker

The case-control study by researchers in Italy and Greece included 80 patients with Sjögren-related MALT lymphoma matched to controls with Sjögren disease who did not have lymphoma.

“We showed that rheumatoid factor positivity at the time of Sjögren’s disease diagnosis serves as the most reliable and temporally distant independent predictor of MALT lymphoma development,” lead author Andreas Goules, MD, a pathophysiologist at the National and Kapodistrian University of Athens, Athens, Greece, told this news organization.

What Future Studies Should Look At

The studies call for further research into biomarkers for Sjögren disease–related lymphoma and treatment of the disease, both Dr. Mariette and Dr. Goules said.

Dr. Goules said a multicenter prospective study is needed to measure RF positivity and RF titers over time and determine whether higher levels mean an increased risk for lymphoma development or a shorter time interval until lymphoma onset. “Such a study requires a large number of RF-positive Sjögren’s disease patients who would be followed up for a long period of time,” Dr. Goules said.

To further evaluate treatment approaches for Sjögren disease–related lymphoma, Dr. Mariette said, a prospective study should compare the watch-and-wait approach with combination chemotherapy and anti-CD20 therapy. “It would be difficult to run because the primary endpoint would be lymphoma progression–free survival, and the secondary would be Sjögren’s relapse and mortality, but it would take a lot of time,” he said.

He added, “It’s a reason why this retrospective study is important. Maybe if we had another retrospective study reaching the same conclusion, I think it would be very, very strong evidence.”

Funding for the case-control study came from the European Commission–Horizon 2020 program. The retrospective treatment study had no outside funding. Dr. Mariette disclosed financial relationships with AstraZeneca, Bristol-Myers Squibb, Galapagos, GlaxoSmithKline, Novartis, and Pfizer. Dr. Alderuccio, Dr. Goules, and Dr. Baer had no relevant relationships to disclose.

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

TOPLINE:

Higher rheumatoid arthritis (RA) disease activity is associated with an accelerated kidney function decline and increased risk for chronic kidney disease (CKD) stages G3a and G3b.

METHODOLOGY:

• Researchers analyzed data from the CorEvitas RA registry, a prospective observational cohort in the United States, between 2001 and 2022, to evaluate the longitudinal association between RA disease activity and changes in kidney function.
• They included 31,129 patients with RA (median age, 58 years; 76.3% women) who had a baseline estimated glomerular filtration rate (eGFR) ≥ 60 mL/min per 1.73 m² and received treatment with disease-modifying antirheumatic drugs (DMARDs).
• The participants were categorized into those in remission (n = 6647) and those with low (n = 10,028), moderate (n = 8548), and high (n = 5906) disease activity based on the time-averaged Clinical Disease Activity Index and followed for a median duration of 3.5 years.
• The primary outcome was a longitudinal change in eGFR, and the secondary outcomes were the development of CKD stage G3a (eGFR < 60 mL/min/1.73 m2) and stage G3b (eGFR < 45 mL/min/1.73 m2).

TAKEAWAY:

• Higher RA disease activity was associated with a faster decline in eGFR, with those having moderate and high RA disease activity experiencing an additional mean annual decline of 0.17 mL/min per 1.73 m² and 0.18 mL/min per 1.73 m², respectively, compared with those in remission.
• The decline in annual eGFR was even more accelerated when patients had consistently high disease activity since the time of enrollment (−0.43 mL/min per 1.73 m²).
• Patients with high RA disease activity had a 1.27 times (adjusted hazard ratio, 1.27; 95% CI, 1.05-1.52) higher risk of developing CKD stage G3a and a 1.93 times (aHR, 1.93; 95% CI, 1.16-3.20) higher risk for CKD stage G3b, compared with those in remission.

IN PRACTICE:

“This study suggests that controlling disease activity may potentially contribute to preserving kidney function in patients with RA,” the authors wrote.

SOURCE:

This study was led by Sho Fukui, MD, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital and Harvard Medical School, both in Boston, Massachusetts, and was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

This study relied on serum creatinine and not cystatin C to estimate kidney function. It also did not collect information on the severity of comorbidities, which may have introduced residual confounding. Further studies are warranted to check the effect of DMARD therapy on renal function.

DISCLOSURES:

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors reported serving as scientific advisers or consultants, receiving consulting fees or salary support, or having other ties with pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Higher rheumatoid arthritis (RA) disease activity is associated with an accelerated kidney function decline and increased risk for chronic kidney disease (CKD) stages G3a and G3b.

METHODOLOGY:

• Researchers analyzed data from the CorEvitas RA registry, a prospective observational cohort in the United States, between 2001 and 2022, to evaluate the longitudinal association between RA disease activity and changes in kidney function.
• They included 31,129 patients with RA (median age, 58 years; 76.3% women) who had a baseline estimated glomerular filtration rate (eGFR) ≥ 60 mL/min per 1.73 m² and received treatment with disease-modifying antirheumatic drugs (DMARDs).
• The participants were categorized into those in remission (n = 6647) and those with low (n = 10,028), moderate (n = 8548), and high (n = 5906) disease activity based on the time-averaged Clinical Disease Activity Index and followed for a median duration of 3.5 years.
• The primary outcome was a longitudinal change in eGFR, and the secondary outcomes were the development of CKD stage G3a (eGFR < 60 mL/min/1.73 m2) and stage G3b (eGFR < 45 mL/min/1.73 m2).

TAKEAWAY:

• Higher RA disease activity was associated with a faster decline in eGFR, with those having moderate and high RA disease activity experiencing an additional mean annual decline of 0.17 mL/min per 1.73 m² and 0.18 mL/min per 1.73 m², respectively, compared with those in remission.
• The decline in annual eGFR was even more accelerated when patients had consistently high disease activity since the time of enrollment (−0.43 mL/min per 1.73 m²).
• Patients with high RA disease activity had a 1.27 times (adjusted hazard ratio, 1.27; 95% CI, 1.05-1.52) higher risk of developing CKD stage G3a and a 1.93 times (aHR, 1.93; 95% CI, 1.16-3.20) higher risk for CKD stage G3b, compared with those in remission.

IN PRACTICE:

“This study suggests that controlling disease activity may potentially contribute to preserving kidney function in patients with RA,” the authors wrote.

SOURCE:

This study was led by Sho Fukui, MD, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital and Harvard Medical School, both in Boston, Massachusetts, and was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

This study relied on serum creatinine and not cystatin C to estimate kidney function. It also did not collect information on the severity of comorbidities, which may have introduced residual confounding. Further studies are warranted to check the effect of DMARD therapy on renal function.

DISCLOSURES:

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors reported serving as scientific advisers or consultants, receiving consulting fees or salary support, or having other ties with pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Higher rheumatoid arthritis (RA) disease activity is associated with an accelerated kidney function decline and increased risk for chronic kidney disease (CKD) stages G3a and G3b.

METHODOLOGY:

• Researchers analyzed data from the CorEvitas RA registry, a prospective observational cohort in the United States, between 2001 and 2022, to evaluate the longitudinal association between RA disease activity and changes in kidney function.
• They included 31,129 patients with RA (median age, 58 years; 76.3% women) who had a baseline estimated glomerular filtration rate (eGFR) ≥ 60 mL/min per 1.73 m² and received treatment with disease-modifying antirheumatic drugs (DMARDs).
• The participants were categorized into those in remission (n = 6647) and those with low (n = 10,028), moderate (n = 8548), and high (n = 5906) disease activity based on the time-averaged Clinical Disease Activity Index and followed for a median duration of 3.5 years.
• The primary outcome was a longitudinal change in eGFR, and the secondary outcomes were the development of CKD stage G3a (eGFR < 60 mL/min/1.73 m2) and stage G3b (eGFR < 45 mL/min/1.73 m2).

TAKEAWAY:

• Higher RA disease activity was associated with a faster decline in eGFR, with those having moderate and high RA disease activity experiencing an additional mean annual decline of 0.17 mL/min per 1.73 m² and 0.18 mL/min per 1.73 m², respectively, compared with those in remission.
• The decline in annual eGFR was even more accelerated when patients had consistently high disease activity since the time of enrollment (−0.43 mL/min per 1.73 m²).
• Patients with high RA disease activity had a 1.27 times (adjusted hazard ratio, 1.27; 95% CI, 1.05-1.52) higher risk of developing CKD stage G3a and a 1.93 times (aHR, 1.93; 95% CI, 1.16-3.20) higher risk for CKD stage G3b, compared with those in remission.

IN PRACTICE:

“This study suggests that controlling disease activity may potentially contribute to preserving kidney function in patients with RA,” the authors wrote.

SOURCE:

This study was led by Sho Fukui, MD, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital and Harvard Medical School, both in Boston, Massachusetts, and was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

This study relied on serum creatinine and not cystatin C to estimate kidney function. It also did not collect information on the severity of comorbidities, which may have introduced residual confounding. Further studies are warranted to check the effect of DMARD therapy on renal function.

DISCLOSURES:

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Some authors reported serving as scientific advisers or consultants, receiving consulting fees or salary support, or having other ties with pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Patients with both rheumatoid arthritis (RA) and atrial fibrillation (AF) have a higher risk for ischemic stroke than those with only AF. They are also less likely to receive oral anticoagulant treatment, which may contribute to this increased stroke risk.

METHODOLOGY:

• Researchers conducted a registry-based retrospective cohort study using the Norwegian Cardio-Rheuma Register to evaluate the risk for ischemic stroke following the diagnosis of AF in patients with or without RA.
• They included 163,595 patients with newly diagnosed AF between 2010 and 2017, of whom 2750 had RA. Patients had to be diagnosed with RA before the diagnosis of AF.
• They also assessed whether patients with RA were less likely to receive oral anticoagulants for stroke prevention within 3 months of AF diagnosis than those without RA.
• The median follow-up time was 2.5 years for patients with RA and 3.0 years for those without RA.
• The primary endpoint was ischemic stroke, which was identified through hospital admissions and visits.

TAKEAWAY:

• At 5 years, patients with both RA and AF showed a higher cumulative incidence of ischemic stroke than those with only AF (7.3% vs 5.0%).
• Among patients with AF, the risk of having a stroke was 25% higher in those with RA than in those without RA (adjusted hazard ratio, 1.25; 95% CI, 1.05-1.50).
• Patients with RA were also less likely to receive treatment with oral anticoagulants than those without RA, driven by concerns over potential interactions with RA medications, bleeding risk, or other factors (adjusted odds ratio, 0.88; 95% CI, 0.80-0.97). 

IN PRACTICE:

“Our study prompts preventive measures such as meticulous cardiovascular risk factor control among patients with RA and AF and raises the question whether the presence of RA should be taken into account when considering OAC [oral anticoagulant] treatment for AF patients,” the authors wrote.

SOURCE:

This study was led by Anne M. Kerola, MD, PhD, Helsinki University Hospital and University of Helsinki in Finland. It was published online in Rheumatology.

LIMITATIONS: 

This study lacked data on smoking, blood pressure measurements, alcohol use, and obesity, which may have affected the comprehensiveness of the findings. The study population was limited to Norway and may not be generalizable to other populations.

DISCLOSURES:

This study was supported by the Olav Thon Foundation, the Research Council of Norway, and the Foundation for Research in Rheumatology. Some authors received speaker fees, participated in advisory boards, served as consultants, or had other ties with some pharmaceutical companies and institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Patients with both rheumatoid arthritis (RA) and atrial fibrillation (AF) have a higher risk for ischemic stroke than those with only AF. They are also less likely to receive oral anticoagulant treatment, which may contribute to this increased stroke risk.

METHODOLOGY:

• Researchers conducted a registry-based retrospective cohort study using the Norwegian Cardio-Rheuma Register to evaluate the risk for ischemic stroke following the diagnosis of AF in patients with or without RA.
• They included 163,595 patients with newly diagnosed AF between 2010 and 2017, of whom 2750 had RA. Patients had to be diagnosed with RA before the diagnosis of AF.
• They also assessed whether patients with RA were less likely to receive oral anticoagulants for stroke prevention within 3 months of AF diagnosis than those without RA.
• The median follow-up time was 2.5 years for patients with RA and 3.0 years for those without RA.
• The primary endpoint was ischemic stroke, which was identified through hospital admissions and visits.

TAKEAWAY:

• At 5 years, patients with both RA and AF showed a higher cumulative incidence of ischemic stroke than those with only AF (7.3% vs 5.0%).
• Among patients with AF, the risk of having a stroke was 25% higher in those with RA than in those without RA (adjusted hazard ratio, 1.25; 95% CI, 1.05-1.50).
• Patients with RA were also less likely to receive treatment with oral anticoagulants than those without RA, driven by concerns over potential interactions with RA medications, bleeding risk, or other factors (adjusted odds ratio, 0.88; 95% CI, 0.80-0.97). 

IN PRACTICE:

“Our study prompts preventive measures such as meticulous cardiovascular risk factor control among patients with RA and AF and raises the question whether the presence of RA should be taken into account when considering OAC [oral anticoagulant] treatment for AF patients,” the authors wrote.

SOURCE:

This study was led by Anne M. Kerola, MD, PhD, Helsinki University Hospital and University of Helsinki in Finland. It was published online in Rheumatology.

LIMITATIONS: 

This study lacked data on smoking, blood pressure measurements, alcohol use, and obesity, which may have affected the comprehensiveness of the findings. The study population was limited to Norway and may not be generalizable to other populations.

DISCLOSURES:

This study was supported by the Olav Thon Foundation, the Research Council of Norway, and the Foundation for Research in Rheumatology. Some authors received speaker fees, participated in advisory boards, served as consultants, or had other ties with some pharmaceutical companies and institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Patients with both rheumatoid arthritis (RA) and atrial fibrillation (AF) have a higher risk for ischemic stroke than those with only AF. They are also less likely to receive oral anticoagulant treatment, which may contribute to this increased stroke risk.

METHODOLOGY:

• Researchers conducted a registry-based retrospective cohort study using the Norwegian Cardio-Rheuma Register to evaluate the risk for ischemic stroke following the diagnosis of AF in patients with or without RA.
• They included 163,595 patients with newly diagnosed AF between 2010 and 2017, of whom 2750 had RA. Patients had to be diagnosed with RA before the diagnosis of AF.
• They also assessed whether patients with RA were less likely to receive oral anticoagulants for stroke prevention within 3 months of AF diagnosis than those without RA.
• The median follow-up time was 2.5 years for patients with RA and 3.0 years for those without RA.
• The primary endpoint was ischemic stroke, which was identified through hospital admissions and visits.

TAKEAWAY:

• At 5 years, patients with both RA and AF showed a higher cumulative incidence of ischemic stroke than those with only AF (7.3% vs 5.0%).
• Among patients with AF, the risk of having a stroke was 25% higher in those with RA than in those without RA (adjusted hazard ratio, 1.25; 95% CI, 1.05-1.50).
• Patients with RA were also less likely to receive treatment with oral anticoagulants than those without RA, driven by concerns over potential interactions with RA medications, bleeding risk, or other factors (adjusted odds ratio, 0.88; 95% CI, 0.80-0.97). 

IN PRACTICE:

“Our study prompts preventive measures such as meticulous cardiovascular risk factor control among patients with RA and AF and raises the question whether the presence of RA should be taken into account when considering OAC [oral anticoagulant] treatment for AF patients,” the authors wrote.

SOURCE:

This study was led by Anne M. Kerola, MD, PhD, Helsinki University Hospital and University of Helsinki in Finland. It was published online in Rheumatology.

LIMITATIONS: 

This study lacked data on smoking, blood pressure measurements, alcohol use, and obesity, which may have affected the comprehensiveness of the findings. The study population was limited to Norway and may not be generalizable to other populations.

DISCLOSURES:

This study was supported by the Olav Thon Foundation, the Research Council of Norway, and the Foundation for Research in Rheumatology. Some authors received speaker fees, participated in advisory boards, served as consultants, or had other ties with some pharmaceutical companies and institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Teclistamab, a T-cell engager that targets B-cell maturation antigen (BCMA), improved disease activity in four patients with refractory autoimmune conditions. In a separately published case report, teclistamab treatment induced remission in a patient with refractory systemic lupus erythematosus (SLE).

BACKGROUND: 

• Chimeric antigen receptor (CAR) T cells or T-cell engagers against CD19 have been effective in small studies of patients with treatment-resistant autoimmune diseases.
• Some patients have disease rooted in long-lived plasma cells that express BCMA but not CD19, making them resistant to CD19 CAR T-cell therapy.
• Teclistamab acts on T cells through CD3 and targets plasmablasts and plasma cells through BCMA.

METHODOLOGY:

• In one case series, researchers administered teclistamab subcutaneously to four patients with autoimmune diseases resistant to more than five immunosuppressants, including rituximab.
• Patient 1 had systemic sclerosis, patient 2 had primary Sjögren disease, patient 3 had idiopathic inflammatory myositis, and patient 4 had rheumatoid arthritis.
• Researchers incrementally increased teclistamab dosage in an inpatient setting: 0.06 mg/kg on day 1, 0.3 mg/kg on day 3, and 1.5 mg/kg on day 5. Patients 2, 3, and 4 received one maintenance dose of 1.5 mg/kg after 4 weeks, and patient 1 received a 1.5-mg/kg dose after 12 weeks.
• In the single case report, the patient with SLE received a step-up dosage of teclistamab (0.06 mg/kg and 0.3 mg/kg) followed by 0.8 mg/kg on day 7. She received 1.5 mg/kg at weeks 2 and 5.

TAKEAWAY: 

• Teclistamab therapy led to significant improvements in disease activity in all four patients, with notable reductions in skin disease, arthritis, and lung function scores.
• Teclistamab therapy had a good safety profile, with no neurotoxicity or myelotoxicity and only lower-grade cytokine release syndrome reported.
• Researchers observed seroconversion of PM-Scl-75, PM-Scl-100, rheumatoid factor, and autoantibodies against mutated citrullinated vimentin and lower levels of autoantibodies ANA, MDAS, SS-A/Ro, SS-B/La, and PL-7 after treatment.
• In the separate case report, the patient reached complete drug-free remission by week 6, as defined by the Systemic Lupus Erythematosus Disease Activity Index 2000.
• The level of anti–double-stranded DNA antibodies in the patient with SLE decreased rapidly, reaching normal range by week 5 and remaining undetectable through week 16.

IN PRACTICE:

“These data show that the targeting of the plasma-cell compartment by a BCMA-targeted T-cell engager is feasible in patients with autoimmune disease. Whether such therapy results in sustained clinical remission warrants further study,” write the authors of the four-patient case series.

SOURCE: 

Melanie Hagen, MD, Friedrich Alexander University Erlangen–Nuremberg, Germany, and colleagues reported their case series online in The New England Journal of Medicine. Tobias Alexander, MD, and colleagues at Charité–Universitätsmedizin Berlin, Germany, also described their single case report in The New England Journal of Medicine.

LIMITATIONS:

The small number of patients limits the generalizability of the findings. The short duration of follow-up may not capture long-term effects and potential late-onset adverse events. The lack of a control group makes it difficult to attribute improvements solely to teclistamab therapy.

DISCLOSURES:

The four-patient case series was supported by grants from the Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, and the European Union. The single case report was supported by grants from the Deutsche Forschungsgemeinschaft and the European Union. Several authors have disclosed financial relationships with pharmaceutical companies, including Janssen Biotech, which markets teclistamab.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Teclistamab, a T-cell engager that targets B-cell maturation antigen (BCMA), improved disease activity in four patients with refractory autoimmune conditions. In a separately published case report, teclistamab treatment induced remission in a patient with refractory systemic lupus erythematosus (SLE).

BACKGROUND: 

• Chimeric antigen receptor (CAR) T cells or T-cell engagers against CD19 have been effective in small studies of patients with treatment-resistant autoimmune diseases.
• Some patients have disease rooted in long-lived plasma cells that express BCMA but not CD19, making them resistant to CD19 CAR T-cell therapy.
• Teclistamab acts on T cells through CD3 and targets plasmablasts and plasma cells through BCMA.

METHODOLOGY:

• In one case series, researchers administered teclistamab subcutaneously to four patients with autoimmune diseases resistant to more than five immunosuppressants, including rituximab.
• Patient 1 had systemic sclerosis, patient 2 had primary Sjögren disease, patient 3 had idiopathic inflammatory myositis, and patient 4 had rheumatoid arthritis.
• Researchers incrementally increased teclistamab dosage in an inpatient setting: 0.06 mg/kg on day 1, 0.3 mg/kg on day 3, and 1.5 mg/kg on day 5. Patients 2, 3, and 4 received one maintenance dose of 1.5 mg/kg after 4 weeks, and patient 1 received a 1.5-mg/kg dose after 12 weeks.
• In the single case report, the patient with SLE received a step-up dosage of teclistamab (0.06 mg/kg and 0.3 mg/kg) followed by 0.8 mg/kg on day 7. She received 1.5 mg/kg at weeks 2 and 5.

TAKEAWAY: 

• Teclistamab therapy led to significant improvements in disease activity in all four patients, with notable reductions in skin disease, arthritis, and lung function scores.
• Teclistamab therapy had a good safety profile, with no neurotoxicity or myelotoxicity and only lower-grade cytokine release syndrome reported.
• Researchers observed seroconversion of PM-Scl-75, PM-Scl-100, rheumatoid factor, and autoantibodies against mutated citrullinated vimentin and lower levels of autoantibodies ANA, MDAS, SS-A/Ro, SS-B/La, and PL-7 after treatment.
• In the separate case report, the patient reached complete drug-free remission by week 6, as defined by the Systemic Lupus Erythematosus Disease Activity Index 2000.
• The level of anti–double-stranded DNA antibodies in the patient with SLE decreased rapidly, reaching normal range by week 5 and remaining undetectable through week 16.

IN PRACTICE:

“These data show that the targeting of the plasma-cell compartment by a BCMA-targeted T-cell engager is feasible in patients with autoimmune disease. Whether such therapy results in sustained clinical remission warrants further study,” write the authors of the four-patient case series.

SOURCE: 

Melanie Hagen, MD, Friedrich Alexander University Erlangen–Nuremberg, Germany, and colleagues reported their case series online in The New England Journal of Medicine. Tobias Alexander, MD, and colleagues at Charité–Universitätsmedizin Berlin, Germany, also described their single case report in The New England Journal of Medicine.

LIMITATIONS:

The small number of patients limits the generalizability of the findings. The short duration of follow-up may not capture long-term effects and potential late-onset adverse events. The lack of a control group makes it difficult to attribute improvements solely to teclistamab therapy.

DISCLOSURES:

The four-patient case series was supported by grants from the Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, and the European Union. The single case report was supported by grants from the Deutsche Forschungsgemeinschaft and the European Union. Several authors have disclosed financial relationships with pharmaceutical companies, including Janssen Biotech, which markets teclistamab.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Teclistamab, a T-cell engager that targets B-cell maturation antigen (BCMA), improved disease activity in four patients with refractory autoimmune conditions. In a separately published case report, teclistamab treatment induced remission in a patient with refractory systemic lupus erythematosus (SLE).

BACKGROUND: 

• Chimeric antigen receptor (CAR) T cells or T-cell engagers against CD19 have been effective in small studies of patients with treatment-resistant autoimmune diseases.
• Some patients have disease rooted in long-lived plasma cells that express BCMA but not CD19, making them resistant to CD19 CAR T-cell therapy.
• Teclistamab acts on T cells through CD3 and targets plasmablasts and plasma cells through BCMA.

METHODOLOGY:

• In one case series, researchers administered teclistamab subcutaneously to four patients with autoimmune diseases resistant to more than five immunosuppressants, including rituximab.
• Patient 1 had systemic sclerosis, patient 2 had primary Sjögren disease, patient 3 had idiopathic inflammatory myositis, and patient 4 had rheumatoid arthritis.
• Researchers incrementally increased teclistamab dosage in an inpatient setting: 0.06 mg/kg on day 1, 0.3 mg/kg on day 3, and 1.5 mg/kg on day 5. Patients 2, 3, and 4 received one maintenance dose of 1.5 mg/kg after 4 weeks, and patient 1 received a 1.5-mg/kg dose after 12 weeks.
• In the single case report, the patient with SLE received a step-up dosage of teclistamab (0.06 mg/kg and 0.3 mg/kg) followed by 0.8 mg/kg on day 7. She received 1.5 mg/kg at weeks 2 and 5.

TAKEAWAY: 

• Teclistamab therapy led to significant improvements in disease activity in all four patients, with notable reductions in skin disease, arthritis, and lung function scores.
• Teclistamab therapy had a good safety profile, with no neurotoxicity or myelotoxicity and only lower-grade cytokine release syndrome reported.
• Researchers observed seroconversion of PM-Scl-75, PM-Scl-100, rheumatoid factor, and autoantibodies against mutated citrullinated vimentin and lower levels of autoantibodies ANA, MDAS, SS-A/Ro, SS-B/La, and PL-7 after treatment.
• In the separate case report, the patient reached complete drug-free remission by week 6, as defined by the Systemic Lupus Erythematosus Disease Activity Index 2000.
• The level of anti–double-stranded DNA antibodies in the patient with SLE decreased rapidly, reaching normal range by week 5 and remaining undetectable through week 16.

IN PRACTICE:

“These data show that the targeting of the plasma-cell compartment by a BCMA-targeted T-cell engager is feasible in patients with autoimmune disease. Whether such therapy results in sustained clinical remission warrants further study,” write the authors of the four-patient case series.

SOURCE: 

Melanie Hagen, MD, Friedrich Alexander University Erlangen–Nuremberg, Germany, and colleagues reported their case series online in The New England Journal of Medicine. Tobias Alexander, MD, and colleagues at Charité–Universitätsmedizin Berlin, Germany, also described their single case report in The New England Journal of Medicine.

LIMITATIONS:

The small number of patients limits the generalizability of the findings. The short duration of follow-up may not capture long-term effects and potential late-onset adverse events. The lack of a control group makes it difficult to attribute improvements solely to teclistamab therapy.

DISCLOSURES:

The four-patient case series was supported by grants from the Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, and the European Union. The single case report was supported by grants from the Deutsche Forschungsgemeinschaft and the European Union. Several authors have disclosed financial relationships with pharmaceutical companies, including Janssen Biotech, which markets teclistamab.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Electronic alerts (e-alerts) for acute kidney injury (AKI) for hospitalized patients are linked to a lower risk for AKI progression, increased consultations with nephrologists, and post-AKI reduced use of nonsteroidal anti-inflammatory drugs (NSAIDs), but not with reduced mortality. 

METHODOLOGY:

• AKI is a common complication in hospitalized patients, leading to increased comorbidities, healthcare costs, and short- and long-term mortality, but the impact of early detection through electronic health care record systems (e-alerts) is unclear.
• Researchers conducted an updated systematic review and meta-analysis to assess the association of e-alerts for AKI with patient outcomes and clinical practice patterns.
• Overall, 13 studies involving 41,837 patients with AKI were included, comparing e-alerts for AKI with standard care or no e-alerts.
• The primary outcomes were mortality, AKI progression, dialysis events, and kidney recovery, and secondary outcomes were nephrologist consultations, post-AKI exposure to NSAIDs and other medications, and hospital length of stay and costs.
• The investigators assessed bias, the certainty of evidence, and whether the primary outcome conclusions of the meta-analysis were premature.

TAKEAWAY:

• The use of e-alerts for AKI was not associated with reduced mortality outcomes compared with no e-alerts (risk ratio [RR], 0.96; 95% CI, 0.89-1.03; 12 studies).
• E-alerts were associated with a reduced risk for AKI progression (RR, 0.91; 95% CI, 0.84-0.99; five studies); however, the results were found to be heterogeneous and possibly premature.
• E-alerts for AKI were also linked to increased nephrologist consultations (RR, 1.45; 95% CI, 1.04-2.02; 11 studies), reduced post-AKI NSAID exposure (RR, 0.75; 95% CI, 0.59-0.95; four studies), and improved AKI documentation (RR, 1.28; 95% CI, 1.04-1.58; eight studies).
• The use of e-alerts for AKI was associated with increased dialysis events (RR, 1.16; 95% CI, 1.05-1.28).

IN PRACTICE:

“We recommend that each hospital establish its own AKI e-alert system and individualized AKI management protocol tailored to its specific needs,” wrote the authors who also suggested the system be “integrated with earlier risk stratification methods, such as the renal angina index, artificial intelligence–based continuous AKI prediction, and care bundle implementation within a clinical decision support system to enhance early diagnosis and management, potentially improving outcomes.”

SOURCE:

This study was led by Jia-Jin Chen, MD, from the Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan. It was published online in JAMA Network Open.

LIMITATIONS: 

The limitations included the scarcity of randomized clinical trials in the meta-analysis. Few studies examined the impact of these e-alerts on the hospital length of stay, healthcare costs, AKI stage progression, and post-AKI kidney recovery, which limited the ability to draw conclusive statements on these aspects. Major adverse kidney events at 28 and 90 days were not reported in any of the enrolled studies, so the impact of AKI e-alerts and increased dialysis events on long-term outcomes remained uncertain.

DISCLOSURES:

The study was supported by grants from the Taiwanese Ministry of Health and Welfare and Linkou Chang Gung Memorial Hospital. The authors declared no conflicts of interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Electronic alerts (e-alerts) for acute kidney injury (AKI) for hospitalized patients are linked to a lower risk for AKI progression, increased consultations with nephrologists, and post-AKI reduced use of nonsteroidal anti-inflammatory drugs (NSAIDs), but not with reduced mortality. 

METHODOLOGY:

• AKI is a common complication in hospitalized patients, leading to increased comorbidities, healthcare costs, and short- and long-term mortality, but the impact of early detection through electronic health care record systems (e-alerts) is unclear.
• Researchers conducted an updated systematic review and meta-analysis to assess the association of e-alerts for AKI with patient outcomes and clinical practice patterns.
• Overall, 13 studies involving 41,837 patients with AKI were included, comparing e-alerts for AKI with standard care or no e-alerts.
• The primary outcomes were mortality, AKI progression, dialysis events, and kidney recovery, and secondary outcomes were nephrologist consultations, post-AKI exposure to NSAIDs and other medications, and hospital length of stay and costs.
• The investigators assessed bias, the certainty of evidence, and whether the primary outcome conclusions of the meta-analysis were premature.

TAKEAWAY:

• The use of e-alerts for AKI was not associated with reduced mortality outcomes compared with no e-alerts (risk ratio [RR], 0.96; 95% CI, 0.89-1.03; 12 studies).
• E-alerts were associated with a reduced risk for AKI progression (RR, 0.91; 95% CI, 0.84-0.99; five studies); however, the results were found to be heterogeneous and possibly premature.
• E-alerts for AKI were also linked to increased nephrologist consultations (RR, 1.45; 95% CI, 1.04-2.02; 11 studies), reduced post-AKI NSAID exposure (RR, 0.75; 95% CI, 0.59-0.95; four studies), and improved AKI documentation (RR, 1.28; 95% CI, 1.04-1.58; eight studies).
• The use of e-alerts for AKI was associated with increased dialysis events (RR, 1.16; 95% CI, 1.05-1.28).

IN PRACTICE:

“We recommend that each hospital establish its own AKI e-alert system and individualized AKI management protocol tailored to its specific needs,” wrote the authors who also suggested the system be “integrated with earlier risk stratification methods, such as the renal angina index, artificial intelligence–based continuous AKI prediction, and care bundle implementation within a clinical decision support system to enhance early diagnosis and management, potentially improving outcomes.”

SOURCE:

This study was led by Jia-Jin Chen, MD, from the Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan. It was published online in JAMA Network Open.

LIMITATIONS: 

The limitations included the scarcity of randomized clinical trials in the meta-analysis. Few studies examined the impact of these e-alerts on the hospital length of stay, healthcare costs, AKI stage progression, and post-AKI kidney recovery, which limited the ability to draw conclusive statements on these aspects. Major adverse kidney events at 28 and 90 days were not reported in any of the enrolled studies, so the impact of AKI e-alerts and increased dialysis events on long-term outcomes remained uncertain.

DISCLOSURES:

The study was supported by grants from the Taiwanese Ministry of Health and Welfare and Linkou Chang Gung Memorial Hospital. The authors declared no conflicts of interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Electronic alerts (e-alerts) for acute kidney injury (AKI) for hospitalized patients are linked to a lower risk for AKI progression, increased consultations with nephrologists, and post-AKI reduced use of nonsteroidal anti-inflammatory drugs (NSAIDs), but not with reduced mortality. 

METHODOLOGY:

• AKI is a common complication in hospitalized patients, leading to increased comorbidities, healthcare costs, and short- and long-term mortality, but the impact of early detection through electronic health care record systems (e-alerts) is unclear.
• Researchers conducted an updated systematic review and meta-analysis to assess the association of e-alerts for AKI with patient outcomes and clinical practice patterns.
• Overall, 13 studies involving 41,837 patients with AKI were included, comparing e-alerts for AKI with standard care or no e-alerts.
• The primary outcomes were mortality, AKI progression, dialysis events, and kidney recovery, and secondary outcomes were nephrologist consultations, post-AKI exposure to NSAIDs and other medications, and hospital length of stay and costs.
• The investigators assessed bias, the certainty of evidence, and whether the primary outcome conclusions of the meta-analysis were premature.

TAKEAWAY:

• The use of e-alerts for AKI was not associated with reduced mortality outcomes compared with no e-alerts (risk ratio [RR], 0.96; 95% CI, 0.89-1.03; 12 studies).
• E-alerts were associated with a reduced risk for AKI progression (RR, 0.91; 95% CI, 0.84-0.99; five studies); however, the results were found to be heterogeneous and possibly premature.
• E-alerts for AKI were also linked to increased nephrologist consultations (RR, 1.45; 95% CI, 1.04-2.02; 11 studies), reduced post-AKI NSAID exposure (RR, 0.75; 95% CI, 0.59-0.95; four studies), and improved AKI documentation (RR, 1.28; 95% CI, 1.04-1.58; eight studies).
• The use of e-alerts for AKI was associated with increased dialysis events (RR, 1.16; 95% CI, 1.05-1.28).

IN PRACTICE:

“We recommend that each hospital establish its own AKI e-alert system and individualized AKI management protocol tailored to its specific needs,” wrote the authors who also suggested the system be “integrated with earlier risk stratification methods, such as the renal angina index, artificial intelligence–based continuous AKI prediction, and care bundle implementation within a clinical decision support system to enhance early diagnosis and management, potentially improving outcomes.”

SOURCE:

This study was led by Jia-Jin Chen, MD, from the Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan City, Taiwan. It was published online in JAMA Network Open.

LIMITATIONS: 

The limitations included the scarcity of randomized clinical trials in the meta-analysis. Few studies examined the impact of these e-alerts on the hospital length of stay, healthcare costs, AKI stage progression, and post-AKI kidney recovery, which limited the ability to draw conclusive statements on these aspects. Major adverse kidney events at 28 and 90 days were not reported in any of the enrolled studies, so the impact of AKI e-alerts and increased dialysis events on long-term outcomes remained uncertain.

DISCLOSURES:

The study was supported by grants from the Taiwanese Ministry of Health and Welfare and Linkou Chang Gung Memorial Hospital. The authors declared no conflicts of interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.