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Few new cancer drugs replace current standards of care
, a new analysis shows.
Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.
“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”
The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.
To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.
The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.
Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.
A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.
Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.
A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.
Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.
The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).
The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”
The study was funded by a grant from Arnold Ventures.
A version of this article first appeared on Medscape.com.
, a new analysis shows.
Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.
“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”
The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.
To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.
The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.
Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.
A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.
Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.
A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.
Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.
The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).
The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”
The study was funded by a grant from Arnold Ventures.
A version of this article first appeared on Medscape.com.
, a new analysis shows.
Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.
“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”
The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.
To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.
The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.
Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.
A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.
Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.
A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.
Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.
The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).
The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”
The study was funded by a grant from Arnold Ventures.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Symptoms, not pelvic exams, pick up most endometrial cancer recurrences
Only 8.5% of endometrial cancer recurrences were caught by routine pelvic exams in asymptomatic women in a review of 234 cases at the University of Wisconsin–Madison.
It was a much lower rate than previously reported. Asymptomatic exams picked up just 4% of recurrences among high-risk women and 14% in low-risk women.
The findings are important as cancer care shifts away from in-person follow-up – including pelvic exams – to telemedicine in the wake of the COVID-19 pandemic, said investigators who were led by University of Wisconsin medical student Hailey Milakovich.
Physicians should reassure patients and providers anxious about skipping routine pelvic exams, she said. There’s a “relatively low risk of missing an endometrial cancer recurrence when forgoing pelvic examination. This information ... is especially relevant in the era of increased use of telemedicine.”
Patient symptoms, such a pain and vaginal bleeding, were by far how most recurrences were caught, accounting for almost 80% of detections among low-risk women and 60% among high-risk patients. It highlights the importance of telling women what to report to their providers, Ms. Milakovich said when she recently presented her study at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
“Our hope is that this information will help us better counsel our patients regarding the risk of” missing an exam, she said.
The findings speak to an ongoing question in gynecologic oncology: how intensely do endometrial cancer patients need to be followed after curative-intent treatment?
COVID-19 brought the issue to a head
Women who typically would have had several pelvic exams a year were channeled to virtual office visits and not pelvic exams. The move caused “some level of anxiety” for both patients and providers, Ms. Milakovich said.
The study discussant, University of California, Los Angeles, gynecologic oncologist Ritu Salani, MD, said the Wisconsin team found something “really important.”
The “investigators suggest there’s a really low utility for pelvic examinations. I think this is very timely” as health care shifts to telemedicine. It reduces the burden on women when “they don’t have to come in and pay for parking, take time off from work, or find childcare,” she said. The findings are also in line with a larger study on the issue, the TOTEM trial with almost 2,000 women, which found no overall survival benefit with intensive monitoring.
The dogma is that routine pelvic exams pick up almost 70% of endometrial cancer recurrences. The Wisconsin team wanted to test that in their 234 recurrence patients from 2010-2019, all of whom had clear documentation about how their recurrences were detected.
Ninety-nine women had low-risk disease, defined as stage 1 or 2, grade 1 or 2 endometrioid histology; 135 women had high-risk cancer, which was defined as stage 3 or 4 endometrioid disease or any other histology.
Recurrence was detected by symptoms in 78.8% of the low-risk group. Asymptomatic pelvic exams detected 14.1% of recurrences; imaging found 2%; biomarkers found 2%; and recurrences were detected by incidental findings in the rest.
Recurrence was found in the high-risk group by symptoms in 60%, imaging in 17.8%, biomarkers in 14.1%, asymptomatic pelvic exams in 4.4%, and incidental findings in 3.7%.
Patients were an average of 68.5 years old, 95.3% were White, and they lived an average of 50.2 miles from the university.
There was no commercial funding for the study. Ms. Milakovich didn’t have any disclosures. Dr. Salani is an adviser for GlaxoSmithKline, Merck, Genentech, and other companies.
Only 8.5% of endometrial cancer recurrences were caught by routine pelvic exams in asymptomatic women in a review of 234 cases at the University of Wisconsin–Madison.
It was a much lower rate than previously reported. Asymptomatic exams picked up just 4% of recurrences among high-risk women and 14% in low-risk women.
The findings are important as cancer care shifts away from in-person follow-up – including pelvic exams – to telemedicine in the wake of the COVID-19 pandemic, said investigators who were led by University of Wisconsin medical student Hailey Milakovich.
Physicians should reassure patients and providers anxious about skipping routine pelvic exams, she said. There’s a “relatively low risk of missing an endometrial cancer recurrence when forgoing pelvic examination. This information ... is especially relevant in the era of increased use of telemedicine.”
Patient symptoms, such a pain and vaginal bleeding, were by far how most recurrences were caught, accounting for almost 80% of detections among low-risk women and 60% among high-risk patients. It highlights the importance of telling women what to report to their providers, Ms. Milakovich said when she recently presented her study at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
“Our hope is that this information will help us better counsel our patients regarding the risk of” missing an exam, she said.
The findings speak to an ongoing question in gynecologic oncology: how intensely do endometrial cancer patients need to be followed after curative-intent treatment?
COVID-19 brought the issue to a head
Women who typically would have had several pelvic exams a year were channeled to virtual office visits and not pelvic exams. The move caused “some level of anxiety” for both patients and providers, Ms. Milakovich said.
The study discussant, University of California, Los Angeles, gynecologic oncologist Ritu Salani, MD, said the Wisconsin team found something “really important.”
The “investigators suggest there’s a really low utility for pelvic examinations. I think this is very timely” as health care shifts to telemedicine. It reduces the burden on women when “they don’t have to come in and pay for parking, take time off from work, or find childcare,” she said. The findings are also in line with a larger study on the issue, the TOTEM trial with almost 2,000 women, which found no overall survival benefit with intensive monitoring.
The dogma is that routine pelvic exams pick up almost 70% of endometrial cancer recurrences. The Wisconsin team wanted to test that in their 234 recurrence patients from 2010-2019, all of whom had clear documentation about how their recurrences were detected.
Ninety-nine women had low-risk disease, defined as stage 1 or 2, grade 1 or 2 endometrioid histology; 135 women had high-risk cancer, which was defined as stage 3 or 4 endometrioid disease or any other histology.
Recurrence was detected by symptoms in 78.8% of the low-risk group. Asymptomatic pelvic exams detected 14.1% of recurrences; imaging found 2%; biomarkers found 2%; and recurrences were detected by incidental findings in the rest.
Recurrence was found in the high-risk group by symptoms in 60%, imaging in 17.8%, biomarkers in 14.1%, asymptomatic pelvic exams in 4.4%, and incidental findings in 3.7%.
Patients were an average of 68.5 years old, 95.3% were White, and they lived an average of 50.2 miles from the university.
There was no commercial funding for the study. Ms. Milakovich didn’t have any disclosures. Dr. Salani is an adviser for GlaxoSmithKline, Merck, Genentech, and other companies.
Only 8.5% of endometrial cancer recurrences were caught by routine pelvic exams in asymptomatic women in a review of 234 cases at the University of Wisconsin–Madison.
It was a much lower rate than previously reported. Asymptomatic exams picked up just 4% of recurrences among high-risk women and 14% in low-risk women.
The findings are important as cancer care shifts away from in-person follow-up – including pelvic exams – to telemedicine in the wake of the COVID-19 pandemic, said investigators who were led by University of Wisconsin medical student Hailey Milakovich.
Physicians should reassure patients and providers anxious about skipping routine pelvic exams, she said. There’s a “relatively low risk of missing an endometrial cancer recurrence when forgoing pelvic examination. This information ... is especially relevant in the era of increased use of telemedicine.”
Patient symptoms, such a pain and vaginal bleeding, were by far how most recurrences were caught, accounting for almost 80% of detections among low-risk women and 60% among high-risk patients. It highlights the importance of telling women what to report to their providers, Ms. Milakovich said when she recently presented her study at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
“Our hope is that this information will help us better counsel our patients regarding the risk of” missing an exam, she said.
The findings speak to an ongoing question in gynecologic oncology: how intensely do endometrial cancer patients need to be followed after curative-intent treatment?
COVID-19 brought the issue to a head
Women who typically would have had several pelvic exams a year were channeled to virtual office visits and not pelvic exams. The move caused “some level of anxiety” for both patients and providers, Ms. Milakovich said.
The study discussant, University of California, Los Angeles, gynecologic oncologist Ritu Salani, MD, said the Wisconsin team found something “really important.”
The “investigators suggest there’s a really low utility for pelvic examinations. I think this is very timely” as health care shifts to telemedicine. It reduces the burden on women when “they don’t have to come in and pay for parking, take time off from work, or find childcare,” she said. The findings are also in line with a larger study on the issue, the TOTEM trial with almost 2,000 women, which found no overall survival benefit with intensive monitoring.
The dogma is that routine pelvic exams pick up almost 70% of endometrial cancer recurrences. The Wisconsin team wanted to test that in their 234 recurrence patients from 2010-2019, all of whom had clear documentation about how their recurrences were detected.
Ninety-nine women had low-risk disease, defined as stage 1 or 2, grade 1 or 2 endometrioid histology; 135 women had high-risk cancer, which was defined as stage 3 or 4 endometrioid disease or any other histology.
Recurrence was detected by symptoms in 78.8% of the low-risk group. Asymptomatic pelvic exams detected 14.1% of recurrences; imaging found 2%; biomarkers found 2%; and recurrences were detected by incidental findings in the rest.
Recurrence was found in the high-risk group by symptoms in 60%, imaging in 17.8%, biomarkers in 14.1%, asymptomatic pelvic exams in 4.4%, and incidental findings in 3.7%.
Patients were an average of 68.5 years old, 95.3% were White, and they lived an average of 50.2 miles from the university.
There was no commercial funding for the study. Ms. Milakovich didn’t have any disclosures. Dr. Salani is an adviser for GlaxoSmithKline, Merck, Genentech, and other companies.
FROM SGO 2022
Complex surgery 10 times more likely with some ovarian tumors
according to a report at the Society of Gynecologic Oncology annual meeting.
Investigators found that women with those features, compared with those without them, are 10 times more likely to have a high-complexity surgery and almost 27 times more likely to have something other than a complete (RD0) resection.
The findings speak to a common dilemma in advanced ovarian cancer, whether women should have surgery or chemotherapy first. Part of the decision hinges on the likelihood of surgical success, explained lead investigator Diogo Torres, MD, a gynecologic oncologist at Ochsner Health in New Orleans.
He and his team concluded that “preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced [ovarian cancer] to better triage these cases to alternative approaches.”
For years “we’ve been trying to figure out” how best to make the call between primary debulking and neoadjuvant chemotherapy, said Pamela T. Soliman, MD, MPH,a gynecologic oncologist at the University of Texas MD Anderson Cancer Center, Houston, who discussed the abstract at the meeting.
Imaging alone or CA-125 are often used to make the decision, but they’re unreliable. Diagnostic laparoscopy is accurate, but it isn’t used much, she said.
What’s unique about Dr. Torres’s approach is that, by including tumor subtype, it incorporates tumor biology. It makes sense because his team previously found that women with mesenchymal (MES) tumors are more likely than those with other subtypes to have upper abdominal and miliary disease.
The approach needs validation in a larger study, but “I really commend” the team “for incorporating biology into the decision-making because it is clearly a step in the right direction,” Dr. Soliman said.
The study included 129 women who underwent primary debulking surgery for stage 3c or 4 high-grade serous ovarian cancer; 46x women (36%) had MES tumors according to RNA profiling of surgical specimens.
Preoperative CTs were reviewed to assess diaphragmatic disease; gastrohepatic/portahepatis lesions; root of superior mesenteric artery involvement; presence of moderate to severe ascites; intrahepatic lesions, and diffuse peritoneal thickening greater than 4 mm.
Fifty-nine women (46%) were classified as “CT high,” meaning that they had two or more of those findings. Women with no more than one were categorized as “CT low.”
Patients with MES tumors and CT-high disease had the lowest rates of complete resections, 8% versus 46% for the entire cohort and 72% for non-MES, CT-low women. MES, CT-high women were also the most likely to have high-complexity surgery (81% versus 35% in the non-MES, CT-low group).
Adjusting for age, stage, and American Society of Anesthesiologists score, the odds of high-complexity surgery were 9.53 times higher and the odds of something less than a complete resection were 26.73 times greater in MES, CT-high patients, compared with non-MES, CT-low women.
“Further studies are needed to evaluate and validate this model using preoperative biopsy specimens” instead of surgical specimens, the investigators said.
No funding was reported for the work. Dr. Torres didn’t have any disclosures. Dr. Soliman is an adviser for Eisai and Amgen, a consultant for Medscape, and receives research funding from Novartis and Incyte.
according to a report at the Society of Gynecologic Oncology annual meeting.
Investigators found that women with those features, compared with those without them, are 10 times more likely to have a high-complexity surgery and almost 27 times more likely to have something other than a complete (RD0) resection.
The findings speak to a common dilemma in advanced ovarian cancer, whether women should have surgery or chemotherapy first. Part of the decision hinges on the likelihood of surgical success, explained lead investigator Diogo Torres, MD, a gynecologic oncologist at Ochsner Health in New Orleans.
He and his team concluded that “preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced [ovarian cancer] to better triage these cases to alternative approaches.”
For years “we’ve been trying to figure out” how best to make the call between primary debulking and neoadjuvant chemotherapy, said Pamela T. Soliman, MD, MPH,a gynecologic oncologist at the University of Texas MD Anderson Cancer Center, Houston, who discussed the abstract at the meeting.
Imaging alone or CA-125 are often used to make the decision, but they’re unreliable. Diagnostic laparoscopy is accurate, but it isn’t used much, she said.
What’s unique about Dr. Torres’s approach is that, by including tumor subtype, it incorporates tumor biology. It makes sense because his team previously found that women with mesenchymal (MES) tumors are more likely than those with other subtypes to have upper abdominal and miliary disease.
The approach needs validation in a larger study, but “I really commend” the team “for incorporating biology into the decision-making because it is clearly a step in the right direction,” Dr. Soliman said.
The study included 129 women who underwent primary debulking surgery for stage 3c or 4 high-grade serous ovarian cancer; 46x women (36%) had MES tumors according to RNA profiling of surgical specimens.
Preoperative CTs were reviewed to assess diaphragmatic disease; gastrohepatic/portahepatis lesions; root of superior mesenteric artery involvement; presence of moderate to severe ascites; intrahepatic lesions, and diffuse peritoneal thickening greater than 4 mm.
Fifty-nine women (46%) were classified as “CT high,” meaning that they had two or more of those findings. Women with no more than one were categorized as “CT low.”
Patients with MES tumors and CT-high disease had the lowest rates of complete resections, 8% versus 46% for the entire cohort and 72% for non-MES, CT-low women. MES, CT-high women were also the most likely to have high-complexity surgery (81% versus 35% in the non-MES, CT-low group).
Adjusting for age, stage, and American Society of Anesthesiologists score, the odds of high-complexity surgery were 9.53 times higher and the odds of something less than a complete resection were 26.73 times greater in MES, CT-high patients, compared with non-MES, CT-low women.
“Further studies are needed to evaluate and validate this model using preoperative biopsy specimens” instead of surgical specimens, the investigators said.
No funding was reported for the work. Dr. Torres didn’t have any disclosures. Dr. Soliman is an adviser for Eisai and Amgen, a consultant for Medscape, and receives research funding from Novartis and Incyte.
according to a report at the Society of Gynecologic Oncology annual meeting.
Investigators found that women with those features, compared with those without them, are 10 times more likely to have a high-complexity surgery and almost 27 times more likely to have something other than a complete (RD0) resection.
The findings speak to a common dilemma in advanced ovarian cancer, whether women should have surgery or chemotherapy first. Part of the decision hinges on the likelihood of surgical success, explained lead investigator Diogo Torres, MD, a gynecologic oncologist at Ochsner Health in New Orleans.
He and his team concluded that “preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced [ovarian cancer] to better triage these cases to alternative approaches.”
For years “we’ve been trying to figure out” how best to make the call between primary debulking and neoadjuvant chemotherapy, said Pamela T. Soliman, MD, MPH,a gynecologic oncologist at the University of Texas MD Anderson Cancer Center, Houston, who discussed the abstract at the meeting.
Imaging alone or CA-125 are often used to make the decision, but they’re unreliable. Diagnostic laparoscopy is accurate, but it isn’t used much, she said.
What’s unique about Dr. Torres’s approach is that, by including tumor subtype, it incorporates tumor biology. It makes sense because his team previously found that women with mesenchymal (MES) tumors are more likely than those with other subtypes to have upper abdominal and miliary disease.
The approach needs validation in a larger study, but “I really commend” the team “for incorporating biology into the decision-making because it is clearly a step in the right direction,” Dr. Soliman said.
The study included 129 women who underwent primary debulking surgery for stage 3c or 4 high-grade serous ovarian cancer; 46x women (36%) had MES tumors according to RNA profiling of surgical specimens.
Preoperative CTs were reviewed to assess diaphragmatic disease; gastrohepatic/portahepatis lesions; root of superior mesenteric artery involvement; presence of moderate to severe ascites; intrahepatic lesions, and diffuse peritoneal thickening greater than 4 mm.
Fifty-nine women (46%) were classified as “CT high,” meaning that they had two or more of those findings. Women with no more than one were categorized as “CT low.”
Patients with MES tumors and CT-high disease had the lowest rates of complete resections, 8% versus 46% for the entire cohort and 72% for non-MES, CT-low women. MES, CT-high women were also the most likely to have high-complexity surgery (81% versus 35% in the non-MES, CT-low group).
Adjusting for age, stage, and American Society of Anesthesiologists score, the odds of high-complexity surgery were 9.53 times higher and the odds of something less than a complete resection were 26.73 times greater in MES, CT-high patients, compared with non-MES, CT-low women.
“Further studies are needed to evaluate and validate this model using preoperative biopsy specimens” instead of surgical specimens, the investigators said.
No funding was reported for the work. Dr. Torres didn’t have any disclosures. Dr. Soliman is an adviser for Eisai and Amgen, a consultant for Medscape, and receives research funding from Novartis and Incyte.
FROM SGO 2022
FDA approves new immunotherapy combo for metastatic melanoma
in adults and children 12 years or older, according to the drug’s manufacturer, Bristol-Myers Squibb.
Approval was based on the company’s RELATIVITY-047 trial, which found a median progression-free survival (PFS) of 10.1 months among 355 patients randomly assigned to the combination therapy compared with 4.6 months among 359 patients who received nivolumab alone (hazard ratio, 0.75; P = .0055).
In the combination therapy group, 18.9% of patients reported a grade 3/4 drug-related adverse event, compared with 9.7% in the nivolumab group; 14.6% of patients in the combination group had drug-related adverse events leading to discontinuation versus 6.7% of those receiving monotherapy, the company noted in a press release.
Relatlimab is the company’s third immune checkpoint inhibitor to reach the U.S. market, joining the PD-1 inhibitor nivolumab and the CTLA-4 blocker ipilimumab. Relatlimab targets LAG-3, a cell-surface receptor found on activated CD4+ T cells.
Nivolumab plus ipilimumab is currently the standard of care for previously untreated metastatic or inoperable melanoma. Both combinations produce similar PFS, but the incidence of grade 3/4 adverse events is higher with ipilimumab, according to a Jan. 6, 2022, editorial in the New England Journal of Medicine.
Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants.
Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial caused by hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
The approved dosage is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks.
A version of this article first appeared on Medscape.com.
in adults and children 12 years or older, according to the drug’s manufacturer, Bristol-Myers Squibb.
Approval was based on the company’s RELATIVITY-047 trial, which found a median progression-free survival (PFS) of 10.1 months among 355 patients randomly assigned to the combination therapy compared with 4.6 months among 359 patients who received nivolumab alone (hazard ratio, 0.75; P = .0055).
In the combination therapy group, 18.9% of patients reported a grade 3/4 drug-related adverse event, compared with 9.7% in the nivolumab group; 14.6% of patients in the combination group had drug-related adverse events leading to discontinuation versus 6.7% of those receiving monotherapy, the company noted in a press release.
Relatlimab is the company’s third immune checkpoint inhibitor to reach the U.S. market, joining the PD-1 inhibitor nivolumab and the CTLA-4 blocker ipilimumab. Relatlimab targets LAG-3, a cell-surface receptor found on activated CD4+ T cells.
Nivolumab plus ipilimumab is currently the standard of care for previously untreated metastatic or inoperable melanoma. Both combinations produce similar PFS, but the incidence of grade 3/4 adverse events is higher with ipilimumab, according to a Jan. 6, 2022, editorial in the New England Journal of Medicine.
Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants.
Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial caused by hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
The approved dosage is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks.
A version of this article first appeared on Medscape.com.
in adults and children 12 years or older, according to the drug’s manufacturer, Bristol-Myers Squibb.
Approval was based on the company’s RELATIVITY-047 trial, which found a median progression-free survival (PFS) of 10.1 months among 355 patients randomly assigned to the combination therapy compared with 4.6 months among 359 patients who received nivolumab alone (hazard ratio, 0.75; P = .0055).
In the combination therapy group, 18.9% of patients reported a grade 3/4 drug-related adverse event, compared with 9.7% in the nivolumab group; 14.6% of patients in the combination group had drug-related adverse events leading to discontinuation versus 6.7% of those receiving monotherapy, the company noted in a press release.
Relatlimab is the company’s third immune checkpoint inhibitor to reach the U.S. market, joining the PD-1 inhibitor nivolumab and the CTLA-4 blocker ipilimumab. Relatlimab targets LAG-3, a cell-surface receptor found on activated CD4+ T cells.
Nivolumab plus ipilimumab is currently the standard of care for previously untreated metastatic or inoperable melanoma. Both combinations produce similar PFS, but the incidence of grade 3/4 adverse events is higher with ipilimumab, according to a Jan. 6, 2022, editorial in the New England Journal of Medicine.
Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants.
Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial caused by hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
The approved dosage is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks.
A version of this article first appeared on Medscape.com.
Adverse skin effects of cancer immunotherapy reviewed
Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.
, according to members of a European Academy of Dermatology and Venereology (EADV) task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.
Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.
Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.
ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.
“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.
The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.
Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.
Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.
Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.
“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”
Pruritus
ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus.
The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.
Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
Maculopapular rash
Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.
“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.
Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.
Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
Psoriasis-like rash
The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.
“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add.
Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.
The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.
In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).
“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.
The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.
A version of this article first appeared on Medscape.com.
Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.
, according to members of a European Academy of Dermatology and Venereology (EADV) task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.
Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.
Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.
ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.
“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.
The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.
Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.
Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.
Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.
“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”
Pruritus
ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus.
The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.
Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
Maculopapular rash
Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.
“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.
Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.
Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
Psoriasis-like rash
The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.
“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add.
Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.
The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.
In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).
“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.
The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.
A version of this article first appeared on Medscape.com.
Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.
, according to members of a European Academy of Dermatology and Venereology (EADV) task force.
“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.
Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.
Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.
ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.
“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.
The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.
Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.
Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.
Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.
“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”
Pruritus
ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus.
The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.
Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
Maculopapular rash
Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.
“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.
Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.
Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
Psoriasis-like rash
The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.
“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add.
Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.
The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.
In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).
“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.
The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.
A version of this article first appeared on Medscape.com.
Untargeted CT scans leads to overdiagnoses in lung cancer
Such overdiagnosis was illustrated in a recent study from JAMA Internal Medicine of women in Taiwan who were screened for lung cancer using low-dose CT (LDCT).
The study, and the accompanying editorial, pointed out the potential for large databases of routine clinical data to track long-term outcomes, and potentially identify patient subgroups that could benefit from early diagnosis using digital technologies.
The Taiwanese findings echo a similar trend identified in a 2018 post hoc analysis of the Danish Lung Cancer Screening Trial, which estimated that 67.2% of cancers found during that CT screening program for current or former smokers were overdiagnosed. The authors recommended that researchers report rates of overdiagnosis in future screening studies.
The authors of the Taiwan study noted that LDCT is low cost and is frequently offered to individuals who are not considered at high risk of lung cancer, and advertisements in Taiwan often target women, who rarely smoke. The researchers examined data from the Taiwan National Cancer Registry. They looked for evidence of an increased incidence of early-stage detection and reduced incidence of late-stage diagnosis. They found that, from 2004 to 2018, there was an increase of lung cancer incidence from 2.3 to 14.4 per 100,000 (difference, 12.1; 95% confidence interval, 11.3-12.8), but no significant difference in the incidence of late-stage disease (from 18.7 to 19.3 per 100,000; difference, 0.6; 95% CI, –0.5 to 1.7).
“This combination of findings, an additional 12.1 early-stage cancers per 100,000 population and no reduction in late-stage cancers, is strongly suggestive of overdiagnosis,” the authors wrote.
It can be difficult to convince people of the potential harms of overdiagnosis, especially when patients have a nodule removed and remain healthy years later. “It’s very counterintuitive, but it’s a reality, and I think this paper paints the reality very, very clearly,” said Daniel Capurro, MD, PhD, deputy director of the Centre for the Digital Transformation of Health at University of Melbourne, and an author of the editorial.
The issue is that some lung cancers progress so slowly that they may never cause a problem clinically, and their removal can lead to unnecessary cost and risk. And it’s not just cancer. “There are a bunch of other conditions that are defined by specific criteria, but we don’t add the prognosis to that definition. At the individual patient level, we don’t know the prognosis,” Dr. Capurro said.
Dr. Capurro discussed the increasing use of digital technologies like smartphone apps. Machine learning can potentially use such data to diagnose conditions like sleep or mood disorders before they become clinically significant, allowing earlier intervention, but they could also lead to overdiagnosis. Dr. Capurro proposed using longitudinal databases to track patient outcomes, which could be applied to digital screening technologies.
“You might be able to find unknown patterns that help discriminate between these pathological definitions. You should be able to train (digital screens) with the pathological definition plus the disease trajectory as a way to improve that label,” he said.
The study was funded by the Taiwan Ministry of Health and Welfare Clinical Trial Center.
Such overdiagnosis was illustrated in a recent study from JAMA Internal Medicine of women in Taiwan who were screened for lung cancer using low-dose CT (LDCT).
The study, and the accompanying editorial, pointed out the potential for large databases of routine clinical data to track long-term outcomes, and potentially identify patient subgroups that could benefit from early diagnosis using digital technologies.
The Taiwanese findings echo a similar trend identified in a 2018 post hoc analysis of the Danish Lung Cancer Screening Trial, which estimated that 67.2% of cancers found during that CT screening program for current or former smokers were overdiagnosed. The authors recommended that researchers report rates of overdiagnosis in future screening studies.
The authors of the Taiwan study noted that LDCT is low cost and is frequently offered to individuals who are not considered at high risk of lung cancer, and advertisements in Taiwan often target women, who rarely smoke. The researchers examined data from the Taiwan National Cancer Registry. They looked for evidence of an increased incidence of early-stage detection and reduced incidence of late-stage diagnosis. They found that, from 2004 to 2018, there was an increase of lung cancer incidence from 2.3 to 14.4 per 100,000 (difference, 12.1; 95% confidence interval, 11.3-12.8), but no significant difference in the incidence of late-stage disease (from 18.7 to 19.3 per 100,000; difference, 0.6; 95% CI, –0.5 to 1.7).
“This combination of findings, an additional 12.1 early-stage cancers per 100,000 population and no reduction in late-stage cancers, is strongly suggestive of overdiagnosis,” the authors wrote.
It can be difficult to convince people of the potential harms of overdiagnosis, especially when patients have a nodule removed and remain healthy years later. “It’s very counterintuitive, but it’s a reality, and I think this paper paints the reality very, very clearly,” said Daniel Capurro, MD, PhD, deputy director of the Centre for the Digital Transformation of Health at University of Melbourne, and an author of the editorial.
The issue is that some lung cancers progress so slowly that they may never cause a problem clinically, and their removal can lead to unnecessary cost and risk. And it’s not just cancer. “There are a bunch of other conditions that are defined by specific criteria, but we don’t add the prognosis to that definition. At the individual patient level, we don’t know the prognosis,” Dr. Capurro said.
Dr. Capurro discussed the increasing use of digital technologies like smartphone apps. Machine learning can potentially use such data to diagnose conditions like sleep or mood disorders before they become clinically significant, allowing earlier intervention, but they could also lead to overdiagnosis. Dr. Capurro proposed using longitudinal databases to track patient outcomes, which could be applied to digital screening technologies.
“You might be able to find unknown patterns that help discriminate between these pathological definitions. You should be able to train (digital screens) with the pathological definition plus the disease trajectory as a way to improve that label,” he said.
The study was funded by the Taiwan Ministry of Health and Welfare Clinical Trial Center.
Such overdiagnosis was illustrated in a recent study from JAMA Internal Medicine of women in Taiwan who were screened for lung cancer using low-dose CT (LDCT).
The study, and the accompanying editorial, pointed out the potential for large databases of routine clinical data to track long-term outcomes, and potentially identify patient subgroups that could benefit from early diagnosis using digital technologies.
The Taiwanese findings echo a similar trend identified in a 2018 post hoc analysis of the Danish Lung Cancer Screening Trial, which estimated that 67.2% of cancers found during that CT screening program for current or former smokers were overdiagnosed. The authors recommended that researchers report rates of overdiagnosis in future screening studies.
The authors of the Taiwan study noted that LDCT is low cost and is frequently offered to individuals who are not considered at high risk of lung cancer, and advertisements in Taiwan often target women, who rarely smoke. The researchers examined data from the Taiwan National Cancer Registry. They looked for evidence of an increased incidence of early-stage detection and reduced incidence of late-stage diagnosis. They found that, from 2004 to 2018, there was an increase of lung cancer incidence from 2.3 to 14.4 per 100,000 (difference, 12.1; 95% confidence interval, 11.3-12.8), but no significant difference in the incidence of late-stage disease (from 18.7 to 19.3 per 100,000; difference, 0.6; 95% CI, –0.5 to 1.7).
“This combination of findings, an additional 12.1 early-stage cancers per 100,000 population and no reduction in late-stage cancers, is strongly suggestive of overdiagnosis,” the authors wrote.
It can be difficult to convince people of the potential harms of overdiagnosis, especially when patients have a nodule removed and remain healthy years later. “It’s very counterintuitive, but it’s a reality, and I think this paper paints the reality very, very clearly,” said Daniel Capurro, MD, PhD, deputy director of the Centre for the Digital Transformation of Health at University of Melbourne, and an author of the editorial.
The issue is that some lung cancers progress so slowly that they may never cause a problem clinically, and their removal can lead to unnecessary cost and risk. And it’s not just cancer. “There are a bunch of other conditions that are defined by specific criteria, but we don’t add the prognosis to that definition. At the individual patient level, we don’t know the prognosis,” Dr. Capurro said.
Dr. Capurro discussed the increasing use of digital technologies like smartphone apps. Machine learning can potentially use such data to diagnose conditions like sleep or mood disorders before they become clinically significant, allowing earlier intervention, but they could also lead to overdiagnosis. Dr. Capurro proposed using longitudinal databases to track patient outcomes, which could be applied to digital screening technologies.
“You might be able to find unknown patterns that help discriminate between these pathological definitions. You should be able to train (digital screens) with the pathological definition plus the disease trajectory as a way to improve that label,” he said.
The study was funded by the Taiwan Ministry of Health and Welfare Clinical Trial Center.
FROM JAMA INTERNAL MEDICINE
Ways to lessen toxic effects of chemo in older adults
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.1-3
Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
Geriatric assessment and chemotherapy-related toxic effects
A cluster randomized trial1 at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.
The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.
The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
Geriatric assessment in community oncology practices
A recent study by Supriya G. Mohile, MD, and colleagues2 is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.
The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
Geriatric assessment and oncologist-patient communication
A secondary analysis3 of data from Dr. Mohile and colleagues2 evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.
In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.
Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.
References
1. Li D et al. JAMA Oncol. 2021;7:e214158.
2. Mohile SG et al. Lancet. 2021;398:1894-1904.
3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.
A version of this article first appeared on Medscape.com.
FDA approves first PARP inhibitor for early BRCA+ breast cancer
BRCA+ breast cancer
Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.
The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.
The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.
The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.
Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.
The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.
A version of this article first appeared on Medscape.com.
Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.
The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.
The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.
The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.
Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.
The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.
A version of this article first appeared on Medscape.com.
Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.
The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.
The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.
The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.
Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.
The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.
A version of this article first appeared on Medscape.com.
BRCA+ breast cancer
BRCA+ breast cancer
Registry data support lowering CRC screening age to 45
Approximately one-third of people between 45 and 49 years of age who undergo colonoscopies have neoplastic colorectal pathology, according to a retrospective analysis.
According to the researchers, led by Parth Trivedi, MD, of the Icahn School of Medicine at Mount Sinai, New York, there has progressively been a “disturbing” rise in early-onset colorectal cancer (CRC) in the United States, which has prompted guidelines from the American Cancer Society to the U.S. Preventive Services Task Force to recommend lowering the CRC screening starting age to 45 years old for average-risk individuals. Despite these recommendations, little research to date has fully characterized the prevalence of colorectal neoplasia in individuals younger than the currently recommended CRC onset screening age of 50 years.
Dr. Trivedi and colleagues, who published their study findings in Gastroenterology, retrospectively reviewed colonoscopy data recorded in the Gastrointestinal Quality Improvement Consortium Registry to address the current knowledge gaps on early-onset CRC. Collected data were for procedures conducted at 123 AMSURG ambulatory endoscopy centers across 29 states between January 2014 and February 2021. In total, 2,921,816 colonoscopies during the study period among patients aged 18-54 years were recorded by AMSURG-associated endoscopists; of these, 562,559 met inclusion criteria for high-quality screening or diagnostic colonoscopy procedures.
The researchers pooled a young-onset age group, including patients between the ages of 18 and 49 years old, in whom 145,998 procedures were performed, including 79,934 procedures in patients aged 45-49 years. A comparator group with 336,627 procedures in patients aged 50-54 years was also included in the study. The findings were categorized into CRC, advanced premalignant lesions (APL), and “any neoplasia,” the latter of which included all adenomas, sessile serrated polyps, and CRC.
Among patients aged 18-44 years, the most frequent indications were “diagnostic-other” (45.6%) as well as “diagnostic-bleeding” (39.4%). Among patients between 45 and 49 years of age, the most frequent indications were “screening” (41.4%) and “diagnostic-other” (30.7%). Nearly all (90%) procedures among those aged 50-54 years were for screening.
A multivariable logistic regression identified 5 variables predictive of either APL or CRC in patients between 18 and 49 years of age: increasing age (odds ratio, 1.08; 95% confidence interval, 1.07-1.08; P <0.01), male sex (OR = 1.67; 95% CI, 1.63-1.70; P <0.01), White race (vs. African American: OR = 0.76; 95% CI, 0.73-0.79, P <0.01; vs. Asian: OR = 0.89; 95% CI, 0.84-0.94, P <0.01), family history of CRC (OR = 1.21; 95% CI, 1.16-1.26; P <0.01) and polyps (OR = 1.33; 95% CI, 1.24-1.43; P <0.01), and examinations for bleeding (OR = 1.15; 95% CI, 1.12-1.18; P <0.01) or screening (OR = 1.20; 95% CI, 1.16-1.24; P <0.01).
The prevalence of neoplastic findings in the young-onset age-group increased with increasing age for the categories of any neoplasia, APLs, and CRC. Among patients aged 40-44, 26.59% had any neoplasia, 5.76% had APL, and 0.53% had CRC. In those aged 45-49 years, around 32% had any neoplasia, approximately 7.5% had APLs, and nearly 0.58% had CRC. In the 50- to 54-year-old group, the prevalences of any neoplasia, APL, and CRC were 37.72%, 9.48%, and 0.32%, respectively.
Across all age groups, a family history of CRC was associated with a higher prevalence of any neoplasia and APL. In addition, the rates of any APL and neoplasia in patients with a family history of CRC were comparable to patients who were 5 years older but had no family history of the disease. Across most young-onset age group, individuals with a positive family history had a lower CRC prevalence versus patients with no family history.
The researchers noted that their population data are derived from ambulatory endoscopy centers, which may introduce bias associated with insurance coverage or patient preference to attend specific endoscopic centers. Additionally, the investigators stated that many records on race and ethnicity were missing, further limiting the findings.
“The present analysis of neoplastic colorectal pathology among individuals younger than age 50 suggests that lowering the screening age to 45 for men and women of all races and ethnicities will likely detect important pathology rather frequently,” they concluded. In addition, the researchers noted that the study results “underscore the importance of early messaging to patients and providers in the years leading up to age 45.” Ultimately, improved “awareness of pathology prevalence in individuals younger than age 45 can help guide clinicians in the clinical management of CRC risk,” the researchers wrote.
Several of the researchers reported conflicts of interest with Exact Sciences Corp and Freenome. The study received no industry funding.
Approximately one-third of people between 45 and 49 years of age who undergo colonoscopies have neoplastic colorectal pathology, according to a retrospective analysis.
According to the researchers, led by Parth Trivedi, MD, of the Icahn School of Medicine at Mount Sinai, New York, there has progressively been a “disturbing” rise in early-onset colorectal cancer (CRC) in the United States, which has prompted guidelines from the American Cancer Society to the U.S. Preventive Services Task Force to recommend lowering the CRC screening starting age to 45 years old for average-risk individuals. Despite these recommendations, little research to date has fully characterized the prevalence of colorectal neoplasia in individuals younger than the currently recommended CRC onset screening age of 50 years.
Dr. Trivedi and colleagues, who published their study findings in Gastroenterology, retrospectively reviewed colonoscopy data recorded in the Gastrointestinal Quality Improvement Consortium Registry to address the current knowledge gaps on early-onset CRC. Collected data were for procedures conducted at 123 AMSURG ambulatory endoscopy centers across 29 states between January 2014 and February 2021. In total, 2,921,816 colonoscopies during the study period among patients aged 18-54 years were recorded by AMSURG-associated endoscopists; of these, 562,559 met inclusion criteria for high-quality screening or diagnostic colonoscopy procedures.
The researchers pooled a young-onset age group, including patients between the ages of 18 and 49 years old, in whom 145,998 procedures were performed, including 79,934 procedures in patients aged 45-49 years. A comparator group with 336,627 procedures in patients aged 50-54 years was also included in the study. The findings were categorized into CRC, advanced premalignant lesions (APL), and “any neoplasia,” the latter of which included all adenomas, sessile serrated polyps, and CRC.
Among patients aged 18-44 years, the most frequent indications were “diagnostic-other” (45.6%) as well as “diagnostic-bleeding” (39.4%). Among patients between 45 and 49 years of age, the most frequent indications were “screening” (41.4%) and “diagnostic-other” (30.7%). Nearly all (90%) procedures among those aged 50-54 years were for screening.
A multivariable logistic regression identified 5 variables predictive of either APL or CRC in patients between 18 and 49 years of age: increasing age (odds ratio, 1.08; 95% confidence interval, 1.07-1.08; P <0.01), male sex (OR = 1.67; 95% CI, 1.63-1.70; P <0.01), White race (vs. African American: OR = 0.76; 95% CI, 0.73-0.79, P <0.01; vs. Asian: OR = 0.89; 95% CI, 0.84-0.94, P <0.01), family history of CRC (OR = 1.21; 95% CI, 1.16-1.26; P <0.01) and polyps (OR = 1.33; 95% CI, 1.24-1.43; P <0.01), and examinations for bleeding (OR = 1.15; 95% CI, 1.12-1.18; P <0.01) or screening (OR = 1.20; 95% CI, 1.16-1.24; P <0.01).
The prevalence of neoplastic findings in the young-onset age-group increased with increasing age for the categories of any neoplasia, APLs, and CRC. Among patients aged 40-44, 26.59% had any neoplasia, 5.76% had APL, and 0.53% had CRC. In those aged 45-49 years, around 32% had any neoplasia, approximately 7.5% had APLs, and nearly 0.58% had CRC. In the 50- to 54-year-old group, the prevalences of any neoplasia, APL, and CRC were 37.72%, 9.48%, and 0.32%, respectively.
Across all age groups, a family history of CRC was associated with a higher prevalence of any neoplasia and APL. In addition, the rates of any APL and neoplasia in patients with a family history of CRC were comparable to patients who were 5 years older but had no family history of the disease. Across most young-onset age group, individuals with a positive family history had a lower CRC prevalence versus patients with no family history.
The researchers noted that their population data are derived from ambulatory endoscopy centers, which may introduce bias associated with insurance coverage or patient preference to attend specific endoscopic centers. Additionally, the investigators stated that many records on race and ethnicity were missing, further limiting the findings.
“The present analysis of neoplastic colorectal pathology among individuals younger than age 50 suggests that lowering the screening age to 45 for men and women of all races and ethnicities will likely detect important pathology rather frequently,” they concluded. In addition, the researchers noted that the study results “underscore the importance of early messaging to patients and providers in the years leading up to age 45.” Ultimately, improved “awareness of pathology prevalence in individuals younger than age 45 can help guide clinicians in the clinical management of CRC risk,” the researchers wrote.
Several of the researchers reported conflicts of interest with Exact Sciences Corp and Freenome. The study received no industry funding.
Approximately one-third of people between 45 and 49 years of age who undergo colonoscopies have neoplastic colorectal pathology, according to a retrospective analysis.
According to the researchers, led by Parth Trivedi, MD, of the Icahn School of Medicine at Mount Sinai, New York, there has progressively been a “disturbing” rise in early-onset colorectal cancer (CRC) in the United States, which has prompted guidelines from the American Cancer Society to the U.S. Preventive Services Task Force to recommend lowering the CRC screening starting age to 45 years old for average-risk individuals. Despite these recommendations, little research to date has fully characterized the prevalence of colorectal neoplasia in individuals younger than the currently recommended CRC onset screening age of 50 years.
Dr. Trivedi and colleagues, who published their study findings in Gastroenterology, retrospectively reviewed colonoscopy data recorded in the Gastrointestinal Quality Improvement Consortium Registry to address the current knowledge gaps on early-onset CRC. Collected data were for procedures conducted at 123 AMSURG ambulatory endoscopy centers across 29 states between January 2014 and February 2021. In total, 2,921,816 colonoscopies during the study period among patients aged 18-54 years were recorded by AMSURG-associated endoscopists; of these, 562,559 met inclusion criteria for high-quality screening or diagnostic colonoscopy procedures.
The researchers pooled a young-onset age group, including patients between the ages of 18 and 49 years old, in whom 145,998 procedures were performed, including 79,934 procedures in patients aged 45-49 years. A comparator group with 336,627 procedures in patients aged 50-54 years was also included in the study. The findings were categorized into CRC, advanced premalignant lesions (APL), and “any neoplasia,” the latter of which included all adenomas, sessile serrated polyps, and CRC.
Among patients aged 18-44 years, the most frequent indications were “diagnostic-other” (45.6%) as well as “diagnostic-bleeding” (39.4%). Among patients between 45 and 49 years of age, the most frequent indications were “screening” (41.4%) and “diagnostic-other” (30.7%). Nearly all (90%) procedures among those aged 50-54 years were for screening.
A multivariable logistic regression identified 5 variables predictive of either APL or CRC in patients between 18 and 49 years of age: increasing age (odds ratio, 1.08; 95% confidence interval, 1.07-1.08; P <0.01), male sex (OR = 1.67; 95% CI, 1.63-1.70; P <0.01), White race (vs. African American: OR = 0.76; 95% CI, 0.73-0.79, P <0.01; vs. Asian: OR = 0.89; 95% CI, 0.84-0.94, P <0.01), family history of CRC (OR = 1.21; 95% CI, 1.16-1.26; P <0.01) and polyps (OR = 1.33; 95% CI, 1.24-1.43; P <0.01), and examinations for bleeding (OR = 1.15; 95% CI, 1.12-1.18; P <0.01) or screening (OR = 1.20; 95% CI, 1.16-1.24; P <0.01).
The prevalence of neoplastic findings in the young-onset age-group increased with increasing age for the categories of any neoplasia, APLs, and CRC. Among patients aged 40-44, 26.59% had any neoplasia, 5.76% had APL, and 0.53% had CRC. In those aged 45-49 years, around 32% had any neoplasia, approximately 7.5% had APLs, and nearly 0.58% had CRC. In the 50- to 54-year-old group, the prevalences of any neoplasia, APL, and CRC were 37.72%, 9.48%, and 0.32%, respectively.
Across all age groups, a family history of CRC was associated with a higher prevalence of any neoplasia and APL. In addition, the rates of any APL and neoplasia in patients with a family history of CRC were comparable to patients who were 5 years older but had no family history of the disease. Across most young-onset age group, individuals with a positive family history had a lower CRC prevalence versus patients with no family history.
The researchers noted that their population data are derived from ambulatory endoscopy centers, which may introduce bias associated with insurance coverage or patient preference to attend specific endoscopic centers. Additionally, the investigators stated that many records on race and ethnicity were missing, further limiting the findings.
“The present analysis of neoplastic colorectal pathology among individuals younger than age 50 suggests that lowering the screening age to 45 for men and women of all races and ethnicities will likely detect important pathology rather frequently,” they concluded. In addition, the researchers noted that the study results “underscore the importance of early messaging to patients and providers in the years leading up to age 45.” Ultimately, improved “awareness of pathology prevalence in individuals younger than age 45 can help guide clinicians in the clinical management of CRC risk,” the researchers wrote.
Several of the researchers reported conflicts of interest with Exact Sciences Corp and Freenome. The study received no industry funding.
FROM GASTROENTEROLOGY
New 3D printable stent holds promise for tracheal tumors
Airflow obstruction caused by a malignant tracheal tumor may be managed with a uniquely designed, 3-dimensional (3D) drug-eluting tracheal stent that, at least in animal models so far, works well and may soon be ready for human trials, Chinese investigators are reporting.
The research was published online Jan. 29 in Materials Today Chemistry.
The problems with currently available stents used to treat airflow obstruction are considerable, corresponding author Shengrong Guo, PhD, professor of pharmaceutics, Shanghai Jiao Tong University, China, and colleagues observe. “Tracheal stents physically open up stenosis, recover airway patency, and promptly relieve symptoms, but [they] cannot treat the tumor,” they explain.
“Thus, tracheal restenosis always occurs soon [after], due to progressive tumor growth after stent placement,” they add. Moreover, implanted stents cover the entire tracheal mucosa, thus preventing mucus and sputum discharge, causing airway blockage, the investigators also note. Compounding these flaws is the unalterable fact that delivery of chemotherapy to a malignant tracheal tumor is inefficient, and systemic chemotherapy is always associated with systemic side effects.
All of these issues make it very challenging to treat these tumors, Dr. Guo noted. On the other hand, if there were a means to deliver a chemotherapeutic agent more directly to the disease site – as is done with drug-eluting beads, for example, in other tumor types – then at least drug delivery would be much more efficient. “In this study, a novel tracheal stent was designed with features of a C-shaped and trilayered wall,” the researchers explain.
The gap angle of the newly developed stent is 72°; the inner diameter is 0.5 cm, and it is 2.0 cm in length. The trilayered wall consists of an inner layer of poly (ε-caprolactone) (PCL), which is a biodegradable and implantable material used alone or compounded with other ingredients to print implants. The middle layer consists of magnetic nanoparticle (MNP)–loaded PCL. The authors explain that MNPs have been approved in the U.S. as contrast agents in MRI.
Combined with temperature-responsive materials, MNPs can serve as a source of magnetic thermotherapy as well, which can be used to control drug release and facilitate drug penetration into deeper tissues. The outer layer of the stent contains a paclitaxel-loaded ethylene-vinyl acetate copolymer layer.
“The C-shaped tracheal stents are easily fabricated on a roller by using a self-made specific three-dimensional printer,” the authors explain. They point out that the C-shaped tracheal stents do not cover the entire tracheal wall, and the uncovered gap in that wall allows for normal mucus and sputum discharge.
In vivo evaluation
Once the stents were printed, the researchers evaluated the biosafety and applicability of their C-shaped tracheal stents. Small rabbits weighing 2.5 to 3.0 kg were used as experimental models and were prepared for surgery. The stent was implanted in the rabbits’ tracheas through the use of a simple stent delivery device. During follow-up, the rabbits recovered well without any sign of infection or respiratory complications.
The animals were also eating well within about 5 days of the surgery, and their weight gradually increased, suggesting that the implantation of a stent with intermittent magnetic heating did not lead to any prominent systemic toxicities. “All rabbits were [euthanized] 30 days after the placement of the tracheal stents” and the stent was removed from the rabbits’ trachea, the researchers report.
Close observation of the trachea indicated that the gap left by the C-shaped stent could keep the airway patent without blocking either mucus or sputum discharge. “The stents have good biosafety in rabbits and keep airway patency for 1 month without the occurrence of mucus/sputum blockage after implantation in rabbit trachea,” Dr. Guo and colleagues conclude.
“These results provide a scientific basis for the development of novel self-expandable C-shaped tracheal stents with combinatorial tracheal support and local chemotherapy,” they affirm.
Pediatric airway obstruction
Thus far, the role of 3D printing seems to be most prominent in the treatment of pediatric airway obstruction, where it is used in the surgical planning stages and to create the implant itself. In a systematic review of its use for this, Joshua Stramiello, MD, University of California, San Diego, and colleagues identified 37 original articles, 11 of which discussed 3D printing for surgical planning, and 26 of which discussed 3D printing implants for interventions.
“3D printing for surgical planning not only improves preoperative assessment of surgical approach and stent customization but also helps facilitate patient/family education,” the authors observe. Most of the research so far has been focused on bioresorbable external airway splints and biological grafts, they add – “with both animal studies and human case reports showing good results in improving symptoms.” One clinical series focused on the use of a 3D-printed, patient-specific, bioresorbable airway splint in a cohort of critically ill children with severe tracheobronchomalacia. (Tracheobronchomalacia is the abnormal collapse of the windpipe).
When reported, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. At a median follow-up of 8.5 months, 12 children were long-term survivors, and all but one lived at home. As recently discussed by George Cheng, MD, cofounder of restor3D, a Duke University startup that created the first 3D-printed airway stent using a compressible biocompatible material with properties similar to that of silicone, personalized airway stents have the potential for advance customization, minimize pressure points, and improve airflow dynamics to increase mucus clearance.
In fact, the U.S. Food and Drug Administration has already cleared patient-specific airway stents developed by Thomas Gildea, MD, of the Cleveland Clinic. Both the Duke University and Cleveland Clinic stents have been used in patients, with promising outcomes, Dr. Cheng noted.
The authors and Dr. Stramiello and colleagues have disclosed no relevant financial relationships. Dr. Cheng is the cofounder of restor3D.
A version of this article first appeared on Medscape.com.
Airflow obstruction caused by a malignant tracheal tumor may be managed with a uniquely designed, 3-dimensional (3D) drug-eluting tracheal stent that, at least in animal models so far, works well and may soon be ready for human trials, Chinese investigators are reporting.
The research was published online Jan. 29 in Materials Today Chemistry.
The problems with currently available stents used to treat airflow obstruction are considerable, corresponding author Shengrong Guo, PhD, professor of pharmaceutics, Shanghai Jiao Tong University, China, and colleagues observe. “Tracheal stents physically open up stenosis, recover airway patency, and promptly relieve symptoms, but [they] cannot treat the tumor,” they explain.
“Thus, tracheal restenosis always occurs soon [after], due to progressive tumor growth after stent placement,” they add. Moreover, implanted stents cover the entire tracheal mucosa, thus preventing mucus and sputum discharge, causing airway blockage, the investigators also note. Compounding these flaws is the unalterable fact that delivery of chemotherapy to a malignant tracheal tumor is inefficient, and systemic chemotherapy is always associated with systemic side effects.
All of these issues make it very challenging to treat these tumors, Dr. Guo noted. On the other hand, if there were a means to deliver a chemotherapeutic agent more directly to the disease site – as is done with drug-eluting beads, for example, in other tumor types – then at least drug delivery would be much more efficient. “In this study, a novel tracheal stent was designed with features of a C-shaped and trilayered wall,” the researchers explain.
The gap angle of the newly developed stent is 72°; the inner diameter is 0.5 cm, and it is 2.0 cm in length. The trilayered wall consists of an inner layer of poly (ε-caprolactone) (PCL), which is a biodegradable and implantable material used alone or compounded with other ingredients to print implants. The middle layer consists of magnetic nanoparticle (MNP)–loaded PCL. The authors explain that MNPs have been approved in the U.S. as contrast agents in MRI.
Combined with temperature-responsive materials, MNPs can serve as a source of magnetic thermotherapy as well, which can be used to control drug release and facilitate drug penetration into deeper tissues. The outer layer of the stent contains a paclitaxel-loaded ethylene-vinyl acetate copolymer layer.
“The C-shaped tracheal stents are easily fabricated on a roller by using a self-made specific three-dimensional printer,” the authors explain. They point out that the C-shaped tracheal stents do not cover the entire tracheal wall, and the uncovered gap in that wall allows for normal mucus and sputum discharge.
In vivo evaluation
Once the stents were printed, the researchers evaluated the biosafety and applicability of their C-shaped tracheal stents. Small rabbits weighing 2.5 to 3.0 kg were used as experimental models and were prepared for surgery. The stent was implanted in the rabbits’ tracheas through the use of a simple stent delivery device. During follow-up, the rabbits recovered well without any sign of infection or respiratory complications.
The animals were also eating well within about 5 days of the surgery, and their weight gradually increased, suggesting that the implantation of a stent with intermittent magnetic heating did not lead to any prominent systemic toxicities. “All rabbits were [euthanized] 30 days after the placement of the tracheal stents” and the stent was removed from the rabbits’ trachea, the researchers report.
Close observation of the trachea indicated that the gap left by the C-shaped stent could keep the airway patent without blocking either mucus or sputum discharge. “The stents have good biosafety in rabbits and keep airway patency for 1 month without the occurrence of mucus/sputum blockage after implantation in rabbit trachea,” Dr. Guo and colleagues conclude.
“These results provide a scientific basis for the development of novel self-expandable C-shaped tracheal stents with combinatorial tracheal support and local chemotherapy,” they affirm.
Pediatric airway obstruction
Thus far, the role of 3D printing seems to be most prominent in the treatment of pediatric airway obstruction, where it is used in the surgical planning stages and to create the implant itself. In a systematic review of its use for this, Joshua Stramiello, MD, University of California, San Diego, and colleagues identified 37 original articles, 11 of which discussed 3D printing for surgical planning, and 26 of which discussed 3D printing implants for interventions.
“3D printing for surgical planning not only improves preoperative assessment of surgical approach and stent customization but also helps facilitate patient/family education,” the authors observe. Most of the research so far has been focused on bioresorbable external airway splints and biological grafts, they add – “with both animal studies and human case reports showing good results in improving symptoms.” One clinical series focused on the use of a 3D-printed, patient-specific, bioresorbable airway splint in a cohort of critically ill children with severe tracheobronchomalacia. (Tracheobronchomalacia is the abnormal collapse of the windpipe).
When reported, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. At a median follow-up of 8.5 months, 12 children were long-term survivors, and all but one lived at home. As recently discussed by George Cheng, MD, cofounder of restor3D, a Duke University startup that created the first 3D-printed airway stent using a compressible biocompatible material with properties similar to that of silicone, personalized airway stents have the potential for advance customization, minimize pressure points, and improve airflow dynamics to increase mucus clearance.
In fact, the U.S. Food and Drug Administration has already cleared patient-specific airway stents developed by Thomas Gildea, MD, of the Cleveland Clinic. Both the Duke University and Cleveland Clinic stents have been used in patients, with promising outcomes, Dr. Cheng noted.
The authors and Dr. Stramiello and colleagues have disclosed no relevant financial relationships. Dr. Cheng is the cofounder of restor3D.
A version of this article first appeared on Medscape.com.
Airflow obstruction caused by a malignant tracheal tumor may be managed with a uniquely designed, 3-dimensional (3D) drug-eluting tracheal stent that, at least in animal models so far, works well and may soon be ready for human trials, Chinese investigators are reporting.
The research was published online Jan. 29 in Materials Today Chemistry.
The problems with currently available stents used to treat airflow obstruction are considerable, corresponding author Shengrong Guo, PhD, professor of pharmaceutics, Shanghai Jiao Tong University, China, and colleagues observe. “Tracheal stents physically open up stenosis, recover airway patency, and promptly relieve symptoms, but [they] cannot treat the tumor,” they explain.
“Thus, tracheal restenosis always occurs soon [after], due to progressive tumor growth after stent placement,” they add. Moreover, implanted stents cover the entire tracheal mucosa, thus preventing mucus and sputum discharge, causing airway blockage, the investigators also note. Compounding these flaws is the unalterable fact that delivery of chemotherapy to a malignant tracheal tumor is inefficient, and systemic chemotherapy is always associated with systemic side effects.
All of these issues make it very challenging to treat these tumors, Dr. Guo noted. On the other hand, if there were a means to deliver a chemotherapeutic agent more directly to the disease site – as is done with drug-eluting beads, for example, in other tumor types – then at least drug delivery would be much more efficient. “In this study, a novel tracheal stent was designed with features of a C-shaped and trilayered wall,” the researchers explain.
The gap angle of the newly developed stent is 72°; the inner diameter is 0.5 cm, and it is 2.0 cm in length. The trilayered wall consists of an inner layer of poly (ε-caprolactone) (PCL), which is a biodegradable and implantable material used alone or compounded with other ingredients to print implants. The middle layer consists of magnetic nanoparticle (MNP)–loaded PCL. The authors explain that MNPs have been approved in the U.S. as contrast agents in MRI.
Combined with temperature-responsive materials, MNPs can serve as a source of magnetic thermotherapy as well, which can be used to control drug release and facilitate drug penetration into deeper tissues. The outer layer of the stent contains a paclitaxel-loaded ethylene-vinyl acetate copolymer layer.
“The C-shaped tracheal stents are easily fabricated on a roller by using a self-made specific three-dimensional printer,” the authors explain. They point out that the C-shaped tracheal stents do not cover the entire tracheal wall, and the uncovered gap in that wall allows for normal mucus and sputum discharge.
In vivo evaluation
Once the stents were printed, the researchers evaluated the biosafety and applicability of their C-shaped tracheal stents. Small rabbits weighing 2.5 to 3.0 kg were used as experimental models and were prepared for surgery. The stent was implanted in the rabbits’ tracheas through the use of a simple stent delivery device. During follow-up, the rabbits recovered well without any sign of infection or respiratory complications.
The animals were also eating well within about 5 days of the surgery, and their weight gradually increased, suggesting that the implantation of a stent with intermittent magnetic heating did not lead to any prominent systemic toxicities. “All rabbits were [euthanized] 30 days after the placement of the tracheal stents” and the stent was removed from the rabbits’ trachea, the researchers report.
Close observation of the trachea indicated that the gap left by the C-shaped stent could keep the airway patent without blocking either mucus or sputum discharge. “The stents have good biosafety in rabbits and keep airway patency for 1 month without the occurrence of mucus/sputum blockage after implantation in rabbit trachea,” Dr. Guo and colleagues conclude.
“These results provide a scientific basis for the development of novel self-expandable C-shaped tracheal stents with combinatorial tracheal support and local chemotherapy,” they affirm.
Pediatric airway obstruction
Thus far, the role of 3D printing seems to be most prominent in the treatment of pediatric airway obstruction, where it is used in the surgical planning stages and to create the implant itself. In a systematic review of its use for this, Joshua Stramiello, MD, University of California, San Diego, and colleagues identified 37 original articles, 11 of which discussed 3D printing for surgical planning, and 26 of which discussed 3D printing implants for interventions.
“3D printing for surgical planning not only improves preoperative assessment of surgical approach and stent customization but also helps facilitate patient/family education,” the authors observe. Most of the research so far has been focused on bioresorbable external airway splints and biological grafts, they add – “with both animal studies and human case reports showing good results in improving symptoms.” One clinical series focused on the use of a 3D-printed, patient-specific, bioresorbable airway splint in a cohort of critically ill children with severe tracheobronchomalacia. (Tracheobronchomalacia is the abnormal collapse of the windpipe).
When reported, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. At a median follow-up of 8.5 months, 12 children were long-term survivors, and all but one lived at home. As recently discussed by George Cheng, MD, cofounder of restor3D, a Duke University startup that created the first 3D-printed airway stent using a compressible biocompatible material with properties similar to that of silicone, personalized airway stents have the potential for advance customization, minimize pressure points, and improve airflow dynamics to increase mucus clearance.
In fact, the U.S. Food and Drug Administration has already cleared patient-specific airway stents developed by Thomas Gildea, MD, of the Cleveland Clinic. Both the Duke University and Cleveland Clinic stents have been used in patients, with promising outcomes, Dr. Cheng noted.
The authors and Dr. Stramiello and colleagues have disclosed no relevant financial relationships. Dr. Cheng is the cofounder of restor3D.
A version of this article first appeared on Medscape.com.