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Thermal ablation may reduce residual, recurrent adenomas
Thermal ablation of the defect margin after endoscopic mucosal resection (EMR-T) is associated with reduced recurrence in the treatment of large (≥20-mm) nonpedunculated colorectal polyps (LNPCPs), according to a prospective international cohort study.
Residual or recurrent adenomas (RRAs) are found during 15%-20% of first surveillance endoscopies. EMR-T was previously shown in a randomized trial to be effective at reducing adenoma recurrence during surveillance endoscopy (relative risk, 0.3; P < .01).
The U.S. Multi-Society Task Force currently recommends EMR-T for LNPCPs, but real-world effectiveness remains unknown, wrote Mayenaaz Sidhu, MBBS, of the department of gastroenterology and hepatology at Westmead Hospital in Sydney and colleagues in Gastroenterology. Therefore, they undertook an international, multicenter, prospective trial to evaluate the technique in the real world.
The researchers analyzed data from consecutive patients who were referred for treatment of LNPCPs at six tertiary centers. Between May 2016 and August 2020, the study included 1,049 LNPCPs from 1,049 patients. The mean age was 67.3 years, and the median lesion size was 35 mm. Of LNPCPs, 58.7% were tubulovillous adenomas. EMR was technically successful in 98.9% of cases. Overall, 19.1% of cases required an auxiliary modality to completely remove polypoid tissue; most often this was cold avulsion with adjuvant snare-tip soft coagulation (44.4%).
Complete EMR-T was achieved in 95.4% cases. Reasons for failure included extensive post-EMR defect (n = 29), unstable colonoscope position or difficult access (n = 14), and intraprocedural adverse events (n = 5).
Of 803 patients eligible for surveillance colonoscopy, 94% underwent the procedure at a median interval of 6 months. Overall, RRAs were found in 3% of cases. Among lesions with complete EMR-T, 1.4% (10 of 707) had RRAs at first surveillance colonoscopy versus 27.1% (13 of 48) with incomplete EMR-T (P < .001). In cases with incomplete EMR-T, lesions were larger (median size, 42.50 mm vs. 37.60 mm; P = .03), there was longer procedure time (mean, 60.2 vs. 35.0 minutes; P = .01), and there was a greater likelihood of referral for surgery (8.3% vs. 3.0%; P = .04).
Intraprocedural bleeding occurred in 6% of cases, and endoscopic hemostasis was achieved in all. Clinically significant post-EMR bleeding occurred in 6.8% of cases, 59.2% of which were managed conservatively, and the remainder were evaluated endoscopically. Bleeding was controlled in every case.
Unlike RRA risk scores that use size, morphology, site, and access score, EMR-T can be used proactively to reduce RRA frequency. It is believed to work by thermally ablating microscopic tissue at the margin. The adverse events reported in the current study were similar to a systematic review and meta-analysis.
“These findings clearly support and exceed those of a recent randomized trial for EMR-T in the colorectum. They likely reflect refinements in the performance of EMR-T over time, due to greater technical experience and enhanced confidence in its safety. At its inception, the approach to EMR-T may have been timid, however, as experience grew and the safety of EMR-T became evident, a meticulous approach to uniform and complete thermal ablation of the defect margin became the standard of care,” the authors wrote.
They added that EMR-T has been shown to benefit in complex LNPCPs, including those that have undergone previous excision attempts and those involving the anorectal junction. The procedure has no added cost, since many endoscopists can readily use snare-tip soft coagulation to manage bleeding events.
“Thermal ablation of the defect margin should be viewed as an essential component of high-quality EMR for LNPCPs, consistent with recent recommendations by the U.S. Multi-Society Task Force on Colorectal Cancer,” the authors wrote.
The study was funded by the Cancer Institute of New South Wales, the Gallipoli Medical Research Foundation, and the University of British Columbia. One author reported research support for Olympus, Cook Medical, and Boston Scientific, but the remaining authors disclosed no conflicts.
This prospective multicenter study “seals” it: Margin ablation should be the standard of care following endoscopic resection of large nonpedunculated colorectal polyps! The study results are impressive with an intention-to-treat recurrence rate of 3%, and only 1.4% if complete margin ablation is achieved!
The results surpass those of the randomized controlled trial from the same group (5% recurrence). According to the authors, refinement in using snare tip soft coagulation and ensuring a 2- to 3-mm wide ablation margin likely contributed to these outcomes. It should be noted that each of the 17 participating endoscopists underwent ablation training sessions overseen by the senior author. Although the technique might be easy to learn, the learning curve is unclear. The recurrence rate among endoscopists ranged from 0% to 11%, although the number is too low to make any firm conclusions.
Nevertheless, it appears that the two major obstacles of endoscopic large polyp resection have now been addressed. Clip closure reduces postprocedure bleeding by approximately 50%, and margin ablation minimizes the risk of recurrence! What does it mean for us practicing large polyp resection? We need to select the right method for the right lesion, apply effective means to remove residual polyp, ablate the margin, and close a defect. Other methods may evolve that can also achieve an effective resection, but for now margin ablation with snare tip soft coagulation is effective and should be an integral part.
Heiko Pohl, MD, MPH, is professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H. He reports receiving research grants from Cosmo Pharmaceuticals and from Steris.
This prospective multicenter study “seals” it: Margin ablation should be the standard of care following endoscopic resection of large nonpedunculated colorectal polyps! The study results are impressive with an intention-to-treat recurrence rate of 3%, and only 1.4% if complete margin ablation is achieved!
The results surpass those of the randomized controlled trial from the same group (5% recurrence). According to the authors, refinement in using snare tip soft coagulation and ensuring a 2- to 3-mm wide ablation margin likely contributed to these outcomes. It should be noted that each of the 17 participating endoscopists underwent ablation training sessions overseen by the senior author. Although the technique might be easy to learn, the learning curve is unclear. The recurrence rate among endoscopists ranged from 0% to 11%, although the number is too low to make any firm conclusions.
Nevertheless, it appears that the two major obstacles of endoscopic large polyp resection have now been addressed. Clip closure reduces postprocedure bleeding by approximately 50%, and margin ablation minimizes the risk of recurrence! What does it mean for us practicing large polyp resection? We need to select the right method for the right lesion, apply effective means to remove residual polyp, ablate the margin, and close a defect. Other methods may evolve that can also achieve an effective resection, but for now margin ablation with snare tip soft coagulation is effective and should be an integral part.
Heiko Pohl, MD, MPH, is professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H. He reports receiving research grants from Cosmo Pharmaceuticals and from Steris.
This prospective multicenter study “seals” it: Margin ablation should be the standard of care following endoscopic resection of large nonpedunculated colorectal polyps! The study results are impressive with an intention-to-treat recurrence rate of 3%, and only 1.4% if complete margin ablation is achieved!
The results surpass those of the randomized controlled trial from the same group (5% recurrence). According to the authors, refinement in using snare tip soft coagulation and ensuring a 2- to 3-mm wide ablation margin likely contributed to these outcomes. It should be noted that each of the 17 participating endoscopists underwent ablation training sessions overseen by the senior author. Although the technique might be easy to learn, the learning curve is unclear. The recurrence rate among endoscopists ranged from 0% to 11%, although the number is too low to make any firm conclusions.
Nevertheless, it appears that the two major obstacles of endoscopic large polyp resection have now been addressed. Clip closure reduces postprocedure bleeding by approximately 50%, and margin ablation minimizes the risk of recurrence! What does it mean for us practicing large polyp resection? We need to select the right method for the right lesion, apply effective means to remove residual polyp, ablate the margin, and close a defect. Other methods may evolve that can also achieve an effective resection, but for now margin ablation with snare tip soft coagulation is effective and should be an integral part.
Heiko Pohl, MD, MPH, is professor of medicine at the Geisel School of Medicine at Dartmouth, Hanover, N.H. He reports receiving research grants from Cosmo Pharmaceuticals and from Steris.
Thermal ablation of the defect margin after endoscopic mucosal resection (EMR-T) is associated with reduced recurrence in the treatment of large (≥20-mm) nonpedunculated colorectal polyps (LNPCPs), according to a prospective international cohort study.
Residual or recurrent adenomas (RRAs) are found during 15%-20% of first surveillance endoscopies. EMR-T was previously shown in a randomized trial to be effective at reducing adenoma recurrence during surveillance endoscopy (relative risk, 0.3; P < .01).
The U.S. Multi-Society Task Force currently recommends EMR-T for LNPCPs, but real-world effectiveness remains unknown, wrote Mayenaaz Sidhu, MBBS, of the department of gastroenterology and hepatology at Westmead Hospital in Sydney and colleagues in Gastroenterology. Therefore, they undertook an international, multicenter, prospective trial to evaluate the technique in the real world.
The researchers analyzed data from consecutive patients who were referred for treatment of LNPCPs at six tertiary centers. Between May 2016 and August 2020, the study included 1,049 LNPCPs from 1,049 patients. The mean age was 67.3 years, and the median lesion size was 35 mm. Of LNPCPs, 58.7% were tubulovillous adenomas. EMR was technically successful in 98.9% of cases. Overall, 19.1% of cases required an auxiliary modality to completely remove polypoid tissue; most often this was cold avulsion with adjuvant snare-tip soft coagulation (44.4%).
Complete EMR-T was achieved in 95.4% cases. Reasons for failure included extensive post-EMR defect (n = 29), unstable colonoscope position or difficult access (n = 14), and intraprocedural adverse events (n = 5).
Of 803 patients eligible for surveillance colonoscopy, 94% underwent the procedure at a median interval of 6 months. Overall, RRAs were found in 3% of cases. Among lesions with complete EMR-T, 1.4% (10 of 707) had RRAs at first surveillance colonoscopy versus 27.1% (13 of 48) with incomplete EMR-T (P < .001). In cases with incomplete EMR-T, lesions were larger (median size, 42.50 mm vs. 37.60 mm; P = .03), there was longer procedure time (mean, 60.2 vs. 35.0 minutes; P = .01), and there was a greater likelihood of referral for surgery (8.3% vs. 3.0%; P = .04).
Intraprocedural bleeding occurred in 6% of cases, and endoscopic hemostasis was achieved in all. Clinically significant post-EMR bleeding occurred in 6.8% of cases, 59.2% of which were managed conservatively, and the remainder were evaluated endoscopically. Bleeding was controlled in every case.
Unlike RRA risk scores that use size, morphology, site, and access score, EMR-T can be used proactively to reduce RRA frequency. It is believed to work by thermally ablating microscopic tissue at the margin. The adverse events reported in the current study were similar to a systematic review and meta-analysis.
“These findings clearly support and exceed those of a recent randomized trial for EMR-T in the colorectum. They likely reflect refinements in the performance of EMR-T over time, due to greater technical experience and enhanced confidence in its safety. At its inception, the approach to EMR-T may have been timid, however, as experience grew and the safety of EMR-T became evident, a meticulous approach to uniform and complete thermal ablation of the defect margin became the standard of care,” the authors wrote.
They added that EMR-T has been shown to benefit in complex LNPCPs, including those that have undergone previous excision attempts and those involving the anorectal junction. The procedure has no added cost, since many endoscopists can readily use snare-tip soft coagulation to manage bleeding events.
“Thermal ablation of the defect margin should be viewed as an essential component of high-quality EMR for LNPCPs, consistent with recent recommendations by the U.S. Multi-Society Task Force on Colorectal Cancer,” the authors wrote.
The study was funded by the Cancer Institute of New South Wales, the Gallipoli Medical Research Foundation, and the University of British Columbia. One author reported research support for Olympus, Cook Medical, and Boston Scientific, but the remaining authors disclosed no conflicts.
Thermal ablation of the defect margin after endoscopic mucosal resection (EMR-T) is associated with reduced recurrence in the treatment of large (≥20-mm) nonpedunculated colorectal polyps (LNPCPs), according to a prospective international cohort study.
Residual or recurrent adenomas (RRAs) are found during 15%-20% of first surveillance endoscopies. EMR-T was previously shown in a randomized trial to be effective at reducing adenoma recurrence during surveillance endoscopy (relative risk, 0.3; P < .01).
The U.S. Multi-Society Task Force currently recommends EMR-T for LNPCPs, but real-world effectiveness remains unknown, wrote Mayenaaz Sidhu, MBBS, of the department of gastroenterology and hepatology at Westmead Hospital in Sydney and colleagues in Gastroenterology. Therefore, they undertook an international, multicenter, prospective trial to evaluate the technique in the real world.
The researchers analyzed data from consecutive patients who were referred for treatment of LNPCPs at six tertiary centers. Between May 2016 and August 2020, the study included 1,049 LNPCPs from 1,049 patients. The mean age was 67.3 years, and the median lesion size was 35 mm. Of LNPCPs, 58.7% were tubulovillous adenomas. EMR was technically successful in 98.9% of cases. Overall, 19.1% of cases required an auxiliary modality to completely remove polypoid tissue; most often this was cold avulsion with adjuvant snare-tip soft coagulation (44.4%).
Complete EMR-T was achieved in 95.4% cases. Reasons for failure included extensive post-EMR defect (n = 29), unstable colonoscope position or difficult access (n = 14), and intraprocedural adverse events (n = 5).
Of 803 patients eligible for surveillance colonoscopy, 94% underwent the procedure at a median interval of 6 months. Overall, RRAs were found in 3% of cases. Among lesions with complete EMR-T, 1.4% (10 of 707) had RRAs at first surveillance colonoscopy versus 27.1% (13 of 48) with incomplete EMR-T (P < .001). In cases with incomplete EMR-T, lesions were larger (median size, 42.50 mm vs. 37.60 mm; P = .03), there was longer procedure time (mean, 60.2 vs. 35.0 minutes; P = .01), and there was a greater likelihood of referral for surgery (8.3% vs. 3.0%; P = .04).
Intraprocedural bleeding occurred in 6% of cases, and endoscopic hemostasis was achieved in all. Clinically significant post-EMR bleeding occurred in 6.8% of cases, 59.2% of which were managed conservatively, and the remainder were evaluated endoscopically. Bleeding was controlled in every case.
Unlike RRA risk scores that use size, morphology, site, and access score, EMR-T can be used proactively to reduce RRA frequency. It is believed to work by thermally ablating microscopic tissue at the margin. The adverse events reported in the current study were similar to a systematic review and meta-analysis.
“These findings clearly support and exceed those of a recent randomized trial for EMR-T in the colorectum. They likely reflect refinements in the performance of EMR-T over time, due to greater technical experience and enhanced confidence in its safety. At its inception, the approach to EMR-T may have been timid, however, as experience grew and the safety of EMR-T became evident, a meticulous approach to uniform and complete thermal ablation of the defect margin became the standard of care,” the authors wrote.
They added that EMR-T has been shown to benefit in complex LNPCPs, including those that have undergone previous excision attempts and those involving the anorectal junction. The procedure has no added cost, since many endoscopists can readily use snare-tip soft coagulation to manage bleeding events.
“Thermal ablation of the defect margin should be viewed as an essential component of high-quality EMR for LNPCPs, consistent with recent recommendations by the U.S. Multi-Society Task Force on Colorectal Cancer,” the authors wrote.
The study was funded by the Cancer Institute of New South Wales, the Gallipoli Medical Research Foundation, and the University of British Columbia. One author reported research support for Olympus, Cook Medical, and Boston Scientific, but the remaining authors disclosed no conflicts.
FROM GASTROENTEROLOGY
Updates in clinical practice guidelines for Lyme disease
According to the Centers for Disease Control and Prevention, Lyme disease is the fastest growing vector-borne disease, affecting approximately 300,000 Americans every year. It is caused by the spirochete, Borrelia burgdorferi which is transmitted to humans by the deer tick. Lyme disease is often an overlooked diagnosis for myriad reasons, including inaccurate test results.
Recent guidelines for the prevention, diagnosis, and treatment of Lyme disease have been developed by a panel from the Infectious Disease Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR) using evidence-based recommendations.
Infection prevention
We all know that the best way to treat any disease is by preventing it. The following measures are recommended as tools to prevent infection: personal protective wear, repellents, and removal of the attached tick. Recommended repellents include DEET, picaridin, IR3535, oil of lemon, eucalyptus, para-Menthane-3,8-diol (PMD), 2-undecanone, and permethrin. If a tick is found, it should be removed promptly by mechanical measures, such as with tweezers. The tweezers should be inserted between the tick body and skin to ensure removal of the entire tick. Burning an attached tick or applying a noxious chemical to the tick is not recommended.
Diagnosis
Diagnosing Lyme disease is often difficult given that tests can be negative for some time after a tick bite, even when the infection is present. There is good evidence to show that submitting the removed tick for identification is good practice. However, there is no evidence supporting testing the removed tick for the presence of Borrelia burgdorferi as it does not reliably predict infection in humans. It also is recommended to avoid testing asymptomatic people following a tick bite.
Following a high-risk tick bite, adults and children can be given prophylactic antibiotics within 72 hours. It is not helpful for low-risk bites. If the risk level is uncertain, it is better to observe before giving antibiotics. For adults, a single 200-mg dose of doxycycline can be given. In children, 4.4 mg per kg of body weight, up to 200 mg max, can be used for those under 45 kg.
For patients with a tick exposure and erythema migrans, a clinical diagnosis of Lyme disease can be made without further testing. If the clinical presentation is not typical, it is recommended to do an antibody test on an acute phase serum sample followed by a convalescent serum sample in 2-3 weeks if the initial test is negative. Recommended antibiotics for treatment include doxycycline for 10 days or amoxicillin or cefuroxime for 14 days. If a patient is unable to take these, azithromycin may be used for 7 days.
The guidelines also make recommendations regarding testing for Lyme neuroborreliosis, for which neurologic presentations, for adults with psychiatric illnesses, and for children with developmental/behavioral/psychiatric disorders. They further make recommendations for treatment of Lyme disease involving the brain or spinal column, facial nerve palsy, carditis, cardiomyopathy, and arthritis, which are beyond the scope of this discussion.
As family doctors, we are often the first ones patients call upon after a tick bite. We are the ones who diagnosis and treat Lyme disease, so it is imperative that we stay up to date with current clinical guidelines and practice evidence-based medicine. These most recent guidelines from several specialty societies can provide the answers to many of our patients’ questions. They also serve as a great tool to help with our clinical decision-making regarding tick bites. Lyme disease can be a scary infection for patients but, if we offer them the recommended measures, it doesn’t have to be.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].
According to the Centers for Disease Control and Prevention, Lyme disease is the fastest growing vector-borne disease, affecting approximately 300,000 Americans every year. It is caused by the spirochete, Borrelia burgdorferi which is transmitted to humans by the deer tick. Lyme disease is often an overlooked diagnosis for myriad reasons, including inaccurate test results.
Recent guidelines for the prevention, diagnosis, and treatment of Lyme disease have been developed by a panel from the Infectious Disease Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR) using evidence-based recommendations.
Infection prevention
We all know that the best way to treat any disease is by preventing it. The following measures are recommended as tools to prevent infection: personal protective wear, repellents, and removal of the attached tick. Recommended repellents include DEET, picaridin, IR3535, oil of lemon, eucalyptus, para-Menthane-3,8-diol (PMD), 2-undecanone, and permethrin. If a tick is found, it should be removed promptly by mechanical measures, such as with tweezers. The tweezers should be inserted between the tick body and skin to ensure removal of the entire tick. Burning an attached tick or applying a noxious chemical to the tick is not recommended.
Diagnosis
Diagnosing Lyme disease is often difficult given that tests can be negative for some time after a tick bite, even when the infection is present. There is good evidence to show that submitting the removed tick for identification is good practice. However, there is no evidence supporting testing the removed tick for the presence of Borrelia burgdorferi as it does not reliably predict infection in humans. It also is recommended to avoid testing asymptomatic people following a tick bite.
Following a high-risk tick bite, adults and children can be given prophylactic antibiotics within 72 hours. It is not helpful for low-risk bites. If the risk level is uncertain, it is better to observe before giving antibiotics. For adults, a single 200-mg dose of doxycycline can be given. In children, 4.4 mg per kg of body weight, up to 200 mg max, can be used for those under 45 kg.
For patients with a tick exposure and erythema migrans, a clinical diagnosis of Lyme disease can be made without further testing. If the clinical presentation is not typical, it is recommended to do an antibody test on an acute phase serum sample followed by a convalescent serum sample in 2-3 weeks if the initial test is negative. Recommended antibiotics for treatment include doxycycline for 10 days or amoxicillin or cefuroxime for 14 days. If a patient is unable to take these, azithromycin may be used for 7 days.
The guidelines also make recommendations regarding testing for Lyme neuroborreliosis, for which neurologic presentations, for adults with psychiatric illnesses, and for children with developmental/behavioral/psychiatric disorders. They further make recommendations for treatment of Lyme disease involving the brain or spinal column, facial nerve palsy, carditis, cardiomyopathy, and arthritis, which are beyond the scope of this discussion.
As family doctors, we are often the first ones patients call upon after a tick bite. We are the ones who diagnosis and treat Lyme disease, so it is imperative that we stay up to date with current clinical guidelines and practice evidence-based medicine. These most recent guidelines from several specialty societies can provide the answers to many of our patients’ questions. They also serve as a great tool to help with our clinical decision-making regarding tick bites. Lyme disease can be a scary infection for patients but, if we offer them the recommended measures, it doesn’t have to be.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].
According to the Centers for Disease Control and Prevention, Lyme disease is the fastest growing vector-borne disease, affecting approximately 300,000 Americans every year. It is caused by the spirochete, Borrelia burgdorferi which is transmitted to humans by the deer tick. Lyme disease is often an overlooked diagnosis for myriad reasons, including inaccurate test results.
Recent guidelines for the prevention, diagnosis, and treatment of Lyme disease have been developed by a panel from the Infectious Disease Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR) using evidence-based recommendations.
Infection prevention
We all know that the best way to treat any disease is by preventing it. The following measures are recommended as tools to prevent infection: personal protective wear, repellents, and removal of the attached tick. Recommended repellents include DEET, picaridin, IR3535, oil of lemon, eucalyptus, para-Menthane-3,8-diol (PMD), 2-undecanone, and permethrin. If a tick is found, it should be removed promptly by mechanical measures, such as with tweezers. The tweezers should be inserted between the tick body and skin to ensure removal of the entire tick. Burning an attached tick or applying a noxious chemical to the tick is not recommended.
Diagnosis
Diagnosing Lyme disease is often difficult given that tests can be negative for some time after a tick bite, even when the infection is present. There is good evidence to show that submitting the removed tick for identification is good practice. However, there is no evidence supporting testing the removed tick for the presence of Borrelia burgdorferi as it does not reliably predict infection in humans. It also is recommended to avoid testing asymptomatic people following a tick bite.
Following a high-risk tick bite, adults and children can be given prophylactic antibiotics within 72 hours. It is not helpful for low-risk bites. If the risk level is uncertain, it is better to observe before giving antibiotics. For adults, a single 200-mg dose of doxycycline can be given. In children, 4.4 mg per kg of body weight, up to 200 mg max, can be used for those under 45 kg.
For patients with a tick exposure and erythema migrans, a clinical diagnosis of Lyme disease can be made without further testing. If the clinical presentation is not typical, it is recommended to do an antibody test on an acute phase serum sample followed by a convalescent serum sample in 2-3 weeks if the initial test is negative. Recommended antibiotics for treatment include doxycycline for 10 days or amoxicillin or cefuroxime for 14 days. If a patient is unable to take these, azithromycin may be used for 7 days.
The guidelines also make recommendations regarding testing for Lyme neuroborreliosis, for which neurologic presentations, for adults with psychiatric illnesses, and for children with developmental/behavioral/psychiatric disorders. They further make recommendations for treatment of Lyme disease involving the brain or spinal column, facial nerve palsy, carditis, cardiomyopathy, and arthritis, which are beyond the scope of this discussion.
As family doctors, we are often the first ones patients call upon after a tick bite. We are the ones who diagnosis and treat Lyme disease, so it is imperative that we stay up to date with current clinical guidelines and practice evidence-based medicine. These most recent guidelines from several specialty societies can provide the answers to many of our patients’ questions. They also serve as a great tool to help with our clinical decision-making regarding tick bites. Lyme disease can be a scary infection for patients but, if we offer them the recommended measures, it doesn’t have to be.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].
Medicare rules for CPAP: Nonadherence begets more nonadherence for low-income patients
The relationship between adherence and benefit for those prescribed continuous positive airway pressure (CPAP) devices is clear. However, a Medicare-reimbursement rule that demands adherence blind to circumstances appears to be denying access to many low-income patients, according to an analysis delivered at the annual health policy and advocacy conference sponsored by the American College of Chest Physicians.
Over the past several years, adherence to CPAP has improved substantially following a series of studies that demonstrated the device must be used at least 4 hours per night to achieve improved outcomes. Medicare defines adherence as using the device more than 4 hours per night for 70% of nights (21 nights) during a consecutive 30-day period any time in the first 3 months of initial usage.
However, the studies that show improved adherence show a lag among those in the lowest income quartile, according to Sairam Parthasarathy, MD, director of the Center for Sleep and Circadian Sciences at the University of Arizona, Tucson.
When patients are followed for a year after being prescribed CPAP, the lag for the low-income patients is not seen immediately. Rather, adherence studies show a steady climb in adherence in all income groups initially, but ”right at 90 days there is a marked change,” said Dr. Parthasarathy.
This change happens to coincide with Medicare policy that denies reimbursement for CPAP after 90 days if patients are not using CPAP at least 4 hours per night, which is the threshold associated with benefit.
The correlation between this policy and income disparity is “observational” rather than proven, but Dr. Parthasarathy is confident it is valid. He believes it is a prime example of a health inequity driven by poorly conceived policy.
“The 90-day rule needs to go,” he said, calling the choice of threshold “man-made.” He added: “This is the only disease condition for which a therapy is withheld if it is not used according to some magical threshold. I cannot think of a more draconian policy.”
In an effort to illustrate the problem, he likened this policy to withholding insulin in a diabetes patient judged nonadherent because of a persistently elevated Hb1Ac.
At 90 days, adherence rates remain at a relatively early point in their upwards trajectory in all income groups. One year later, adherence rates are more than twice as high in the highest income relative to the lowest quartile and approaching twofold greater in quartiles 2 and 3.
“It takes time to get used to these devices,” Dr. Parthasarathy explained. Given studies demonstrating that “more is better” with CPAP, whether measured by sleep scales or quality of life, Dr. Parthasarathy advocates strategies to improve adherence, but he questioned an approach that penalizes low-income patients for a definition of nonadherence at an arbitrary point in time. He suggested it is just one example of health policies that ultimately penalize individuals with lower incomes.
“There are millions of dollars spent every year on understanding the genetics of disease, but the biggest influence on how long you live is the ZIP code of where you live,” said Dr. Parthasarathy, referring to ZIP codes as a surrogate for socioeconomic status.
This is not to imply, however, that genetics are irrelevant, Dr. Parthasarathy said. He pointed to data linking genetic traits that determine melanin levels and circadian rhythms. He noted one genotype associated with later bedtimes that is more commonly found in African-Americans and Hispanics. This has relevance to a variety of sleep disorders and other health conditions, but it might serve as a fundamental disadvantage for children with this genotype, Dr. Parthasarathy maintained. He cited a study conducted at his center that found Hispanic children sleep on average 30 minutes less than White children (Sleep Med 2016;18:61-6). The reason was simple. Hispanic children went to bed 30 minutes later but rose at the same time.
The later bedtimes and reduced sleep could potentially be one obstacle among many, such as the need for lower-income patients to hold several jobs, that prevent these patients from becoming accustomed to CPAP at the same speed as wealthier patients, according to Dr. Parthasarathy.
The current Medicare policy that withholds CPAP on the basis of a single definition of nonadherence appears to lead directly to an inequity in treatment of sleep apnea, he maintained. Dr. Parthasarathy, who was a coauthor of a recently published paper on addressing disparities in sleep health (Chest 2021;159:1232-40), described this issue as part of a larger problem of the failure to deliver health care that is sensitive to the cultural and racial differences underlying these inequities.
Kathleen Sarmiento, MD, FCCP, director, VISN 21 Sleep Clinical Resource Hub for the San Francisco VA Health Care System, agreed. “This type of issue is exactly what our committee would like to address,” said Dr. Sarmiento, a member of the CHEST Health Policy and Advocacy Committee and the moderator of the session in which Dr. Parthasarathy presented his data.
The association between the 90-day Medicare rule for CPAP reimbursement and reduced access to this therapy among patients of lower economic status is compelling, she indicated. Within the goal of advocacy for health policies that will reduce inequities, Dr. Sarmiento explained that the committee is attempting to identify and reverse the source of these types of disparity.
“Specific rules or regulations are actionable targets to effect broader change in health care access and health care delivery,” said Dr. Sarmiento, alluding to the mission of the Health Policy and Advocacy Committee.
Dr. Parthasarathy and Dr. Sarmiento report no relevant conflicts of interest.
The relationship between adherence and benefit for those prescribed continuous positive airway pressure (CPAP) devices is clear. However, a Medicare-reimbursement rule that demands adherence blind to circumstances appears to be denying access to many low-income patients, according to an analysis delivered at the annual health policy and advocacy conference sponsored by the American College of Chest Physicians.
Over the past several years, adherence to CPAP has improved substantially following a series of studies that demonstrated the device must be used at least 4 hours per night to achieve improved outcomes. Medicare defines adherence as using the device more than 4 hours per night for 70% of nights (21 nights) during a consecutive 30-day period any time in the first 3 months of initial usage.
However, the studies that show improved adherence show a lag among those in the lowest income quartile, according to Sairam Parthasarathy, MD, director of the Center for Sleep and Circadian Sciences at the University of Arizona, Tucson.
When patients are followed for a year after being prescribed CPAP, the lag for the low-income patients is not seen immediately. Rather, adherence studies show a steady climb in adherence in all income groups initially, but ”right at 90 days there is a marked change,” said Dr. Parthasarathy.
This change happens to coincide with Medicare policy that denies reimbursement for CPAP after 90 days if patients are not using CPAP at least 4 hours per night, which is the threshold associated with benefit.
The correlation between this policy and income disparity is “observational” rather than proven, but Dr. Parthasarathy is confident it is valid. He believes it is a prime example of a health inequity driven by poorly conceived policy.
“The 90-day rule needs to go,” he said, calling the choice of threshold “man-made.” He added: “This is the only disease condition for which a therapy is withheld if it is not used according to some magical threshold. I cannot think of a more draconian policy.”
In an effort to illustrate the problem, he likened this policy to withholding insulin in a diabetes patient judged nonadherent because of a persistently elevated Hb1Ac.
At 90 days, adherence rates remain at a relatively early point in their upwards trajectory in all income groups. One year later, adherence rates are more than twice as high in the highest income relative to the lowest quartile and approaching twofold greater in quartiles 2 and 3.
“It takes time to get used to these devices,” Dr. Parthasarathy explained. Given studies demonstrating that “more is better” with CPAP, whether measured by sleep scales or quality of life, Dr. Parthasarathy advocates strategies to improve adherence, but he questioned an approach that penalizes low-income patients for a definition of nonadherence at an arbitrary point in time. He suggested it is just one example of health policies that ultimately penalize individuals with lower incomes.
“There are millions of dollars spent every year on understanding the genetics of disease, but the biggest influence on how long you live is the ZIP code of where you live,” said Dr. Parthasarathy, referring to ZIP codes as a surrogate for socioeconomic status.
This is not to imply, however, that genetics are irrelevant, Dr. Parthasarathy said. He pointed to data linking genetic traits that determine melanin levels and circadian rhythms. He noted one genotype associated with later bedtimes that is more commonly found in African-Americans and Hispanics. This has relevance to a variety of sleep disorders and other health conditions, but it might serve as a fundamental disadvantage for children with this genotype, Dr. Parthasarathy maintained. He cited a study conducted at his center that found Hispanic children sleep on average 30 minutes less than White children (Sleep Med 2016;18:61-6). The reason was simple. Hispanic children went to bed 30 minutes later but rose at the same time.
The later bedtimes and reduced sleep could potentially be one obstacle among many, such as the need for lower-income patients to hold several jobs, that prevent these patients from becoming accustomed to CPAP at the same speed as wealthier patients, according to Dr. Parthasarathy.
The current Medicare policy that withholds CPAP on the basis of a single definition of nonadherence appears to lead directly to an inequity in treatment of sleep apnea, he maintained. Dr. Parthasarathy, who was a coauthor of a recently published paper on addressing disparities in sleep health (Chest 2021;159:1232-40), described this issue as part of a larger problem of the failure to deliver health care that is sensitive to the cultural and racial differences underlying these inequities.
Kathleen Sarmiento, MD, FCCP, director, VISN 21 Sleep Clinical Resource Hub for the San Francisco VA Health Care System, agreed. “This type of issue is exactly what our committee would like to address,” said Dr. Sarmiento, a member of the CHEST Health Policy and Advocacy Committee and the moderator of the session in which Dr. Parthasarathy presented his data.
The association between the 90-day Medicare rule for CPAP reimbursement and reduced access to this therapy among patients of lower economic status is compelling, she indicated. Within the goal of advocacy for health policies that will reduce inequities, Dr. Sarmiento explained that the committee is attempting to identify and reverse the source of these types of disparity.
“Specific rules or regulations are actionable targets to effect broader change in health care access and health care delivery,” said Dr. Sarmiento, alluding to the mission of the Health Policy and Advocacy Committee.
Dr. Parthasarathy and Dr. Sarmiento report no relevant conflicts of interest.
The relationship between adherence and benefit for those prescribed continuous positive airway pressure (CPAP) devices is clear. However, a Medicare-reimbursement rule that demands adherence blind to circumstances appears to be denying access to many low-income patients, according to an analysis delivered at the annual health policy and advocacy conference sponsored by the American College of Chest Physicians.
Over the past several years, adherence to CPAP has improved substantially following a series of studies that demonstrated the device must be used at least 4 hours per night to achieve improved outcomes. Medicare defines adherence as using the device more than 4 hours per night for 70% of nights (21 nights) during a consecutive 30-day period any time in the first 3 months of initial usage.
However, the studies that show improved adherence show a lag among those in the lowest income quartile, according to Sairam Parthasarathy, MD, director of the Center for Sleep and Circadian Sciences at the University of Arizona, Tucson.
When patients are followed for a year after being prescribed CPAP, the lag for the low-income patients is not seen immediately. Rather, adherence studies show a steady climb in adherence in all income groups initially, but ”right at 90 days there is a marked change,” said Dr. Parthasarathy.
This change happens to coincide with Medicare policy that denies reimbursement for CPAP after 90 days if patients are not using CPAP at least 4 hours per night, which is the threshold associated with benefit.
The correlation between this policy and income disparity is “observational” rather than proven, but Dr. Parthasarathy is confident it is valid. He believes it is a prime example of a health inequity driven by poorly conceived policy.
“The 90-day rule needs to go,” he said, calling the choice of threshold “man-made.” He added: “This is the only disease condition for which a therapy is withheld if it is not used according to some magical threshold. I cannot think of a more draconian policy.”
In an effort to illustrate the problem, he likened this policy to withholding insulin in a diabetes patient judged nonadherent because of a persistently elevated Hb1Ac.
At 90 days, adherence rates remain at a relatively early point in their upwards trajectory in all income groups. One year later, adherence rates are more than twice as high in the highest income relative to the lowest quartile and approaching twofold greater in quartiles 2 and 3.
“It takes time to get used to these devices,” Dr. Parthasarathy explained. Given studies demonstrating that “more is better” with CPAP, whether measured by sleep scales or quality of life, Dr. Parthasarathy advocates strategies to improve adherence, but he questioned an approach that penalizes low-income patients for a definition of nonadherence at an arbitrary point in time. He suggested it is just one example of health policies that ultimately penalize individuals with lower incomes.
“There are millions of dollars spent every year on understanding the genetics of disease, but the biggest influence on how long you live is the ZIP code of where you live,” said Dr. Parthasarathy, referring to ZIP codes as a surrogate for socioeconomic status.
This is not to imply, however, that genetics are irrelevant, Dr. Parthasarathy said. He pointed to data linking genetic traits that determine melanin levels and circadian rhythms. He noted one genotype associated with later bedtimes that is more commonly found in African-Americans and Hispanics. This has relevance to a variety of sleep disorders and other health conditions, but it might serve as a fundamental disadvantage for children with this genotype, Dr. Parthasarathy maintained. He cited a study conducted at his center that found Hispanic children sleep on average 30 minutes less than White children (Sleep Med 2016;18:61-6). The reason was simple. Hispanic children went to bed 30 minutes later but rose at the same time.
The later bedtimes and reduced sleep could potentially be one obstacle among many, such as the need for lower-income patients to hold several jobs, that prevent these patients from becoming accustomed to CPAP at the same speed as wealthier patients, according to Dr. Parthasarathy.
The current Medicare policy that withholds CPAP on the basis of a single definition of nonadherence appears to lead directly to an inequity in treatment of sleep apnea, he maintained. Dr. Parthasarathy, who was a coauthor of a recently published paper on addressing disparities in sleep health (Chest 2021;159:1232-40), described this issue as part of a larger problem of the failure to deliver health care that is sensitive to the cultural and racial differences underlying these inequities.
Kathleen Sarmiento, MD, FCCP, director, VISN 21 Sleep Clinical Resource Hub for the San Francisco VA Health Care System, agreed. “This type of issue is exactly what our committee would like to address,” said Dr. Sarmiento, a member of the CHEST Health Policy and Advocacy Committee and the moderator of the session in which Dr. Parthasarathy presented his data.
The association between the 90-day Medicare rule for CPAP reimbursement and reduced access to this therapy among patients of lower economic status is compelling, she indicated. Within the goal of advocacy for health policies that will reduce inequities, Dr. Sarmiento explained that the committee is attempting to identify and reverse the source of these types of disparity.
“Specific rules or regulations are actionable targets to effect broader change in health care access and health care delivery,” said Dr. Sarmiento, alluding to the mission of the Health Policy and Advocacy Committee.
Dr. Parthasarathy and Dr. Sarmiento report no relevant conflicts of interest.
FROM A HEALTH POLICY AND ADVOCACY CONFERENCE
Mavrilimumab may aid severe COVID-19 recovery
Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.
There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.
The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.
Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).
Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.
Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.
In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.
“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.
“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”
Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia
“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.
She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”
The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.
“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.
Study details and other outcome results
The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.
Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.
The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.
Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.
“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).
“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.
There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).
Timing of mavrilimumab administration and safety
Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”
Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”
No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.
Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.
“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.
“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.
Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.
Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.
Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.
Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.
There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.
The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.
Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).
Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.
Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.
In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.
“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.
“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”
Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia
“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.
She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”
The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.
“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.
Study details and other outcome results
The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.
Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.
The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.
Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.
“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).
“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.
There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).
Timing of mavrilimumab administration and safety
Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”
Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”
No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.
Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.
“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.
“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.
Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.
Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.
Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.
Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.
There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.
The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.
Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).
Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.
Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.
In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.
“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.
“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”
Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia
“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.
She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”
The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.
“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.
Study details and other outcome results
The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.
Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.
The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.
Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.
“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).
“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.
There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).
Timing of mavrilimumab administration and safety
Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”
Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”
No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.
Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.
“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.
“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.
Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.
Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.
Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.
FROM EULAR 2021 CONGRESS
One year after a single RAP treatment, patients give the results high marks
One year after a single treatment of cellulite with the Rapid Acoustic Pulse (RAP) device, 42 out of 43 patients said that they felt good about the results, an interim analysis from a multicenter study showed.
“I think this speaks to the duration of improvement” associated with this treatment, lead study author Elizabeth L. Tanzi, MD, said during the annual conference of the American Society for Laser Medicine and Surgery.
The study is an extension of a prospective pivotal clinical trial that Dr. Tanzi first presented during late-breaking abstract session at the 2020 virtual annual meeting of the American Academy of Dermatology. For the trial, she and her colleagues at four sites evaluated the safety and effectiveness of the RAP device in 62 women who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. In February 2021, the Food and Drug Administration cleared the device for the short-term improvement in the appearance of cellulite.
“The high peak pressure and fast repetition rate of this device will exploit the viscoelastic tissue compared to other acoustic wave devices that are on the market,” said Dr. Tanzi, associate clinical professor of dermatology at George Washington University, Washington. “Those compressed pulses from electronic filtering and reflector shape eliminate cavitation, heat, and pain. So, what we see physically is fiber septa disruption, as well as other nonthermal physical effects.”
She and her colleagues used a specific photography and fixed lighting setup to record the treated areas at baseline, 12 weeks, and 52 weeks, and administered a patient satisfaction questionnaire at 12 and 52 weeks. Prior to treatment, the investigators marked the dimples and ridges intended for treatment. After placing a hydrogel dressing, it took 45-60 minutes to treat both buttocks and thighs with the RAP device. “It was completely noninvasive,” said Dr. Tanzi, who practices in Chevy Chase, Md. “There was no anesthesia used: no incisions and no needles.”
Among 57 patients who were evaluated at 12 weeks, the pain score on a scale of 0-10 was 2.4, while 61.5% strongly agreed and 35.9% agreed that their cellulite appeared improved. In addition, three blinded assessors were able to correctly identify the treated thigh 96% of the time and physician-graded Global Aesthetic Improvement Scale assessments showed 90% improvement of cellulite.
Follow-up analysis
For the current subject satisfaction analysis, the investigators evaluated results from 43 patients in the trial who were followed for at least 52 weeks (a mean of 60 weeks). Of the 43 patients, 30 (69.8%) strongly agreed and 13 (30.2%) agreed that their cellulite “appears improved.” In addition, 29 (67.4%) strongly agreed, 13 (30.2%) agreed, and 1 (2.3%) disagreed with the statement “I feel there is good improvement” of their cellulite.
“Currently, we are evaluating the blinded assessors’ view of these patients and not just going with [findings from] the patient satisfaction survey, but I think these are encouraging results,” Dr. Tanzi said. “We found that 42 out of 43 patients said, ‘yes; I feel that there was good improvement of the area at 52 weeks.’ ”
Dr. Tanzi disclosed that she is a member of the speakers bureau for Eucerin. She is a member of the advisory board for Allergan, Endo Pharmaceuticals, Pulse Biosciences, Sciton, and Soliton. Soliton markets the RAP device.
One year after a single treatment of cellulite with the Rapid Acoustic Pulse (RAP) device, 42 out of 43 patients said that they felt good about the results, an interim analysis from a multicenter study showed.
“I think this speaks to the duration of improvement” associated with this treatment, lead study author Elizabeth L. Tanzi, MD, said during the annual conference of the American Society for Laser Medicine and Surgery.
The study is an extension of a prospective pivotal clinical trial that Dr. Tanzi first presented during late-breaking abstract session at the 2020 virtual annual meeting of the American Academy of Dermatology. For the trial, she and her colleagues at four sites evaluated the safety and effectiveness of the RAP device in 62 women who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. In February 2021, the Food and Drug Administration cleared the device for the short-term improvement in the appearance of cellulite.
“The high peak pressure and fast repetition rate of this device will exploit the viscoelastic tissue compared to other acoustic wave devices that are on the market,” said Dr. Tanzi, associate clinical professor of dermatology at George Washington University, Washington. “Those compressed pulses from electronic filtering and reflector shape eliminate cavitation, heat, and pain. So, what we see physically is fiber septa disruption, as well as other nonthermal physical effects.”
She and her colleagues used a specific photography and fixed lighting setup to record the treated areas at baseline, 12 weeks, and 52 weeks, and administered a patient satisfaction questionnaire at 12 and 52 weeks. Prior to treatment, the investigators marked the dimples and ridges intended for treatment. After placing a hydrogel dressing, it took 45-60 minutes to treat both buttocks and thighs with the RAP device. “It was completely noninvasive,” said Dr. Tanzi, who practices in Chevy Chase, Md. “There was no anesthesia used: no incisions and no needles.”
Among 57 patients who were evaluated at 12 weeks, the pain score on a scale of 0-10 was 2.4, while 61.5% strongly agreed and 35.9% agreed that their cellulite appeared improved. In addition, three blinded assessors were able to correctly identify the treated thigh 96% of the time and physician-graded Global Aesthetic Improvement Scale assessments showed 90% improvement of cellulite.
Follow-up analysis
For the current subject satisfaction analysis, the investigators evaluated results from 43 patients in the trial who were followed for at least 52 weeks (a mean of 60 weeks). Of the 43 patients, 30 (69.8%) strongly agreed and 13 (30.2%) agreed that their cellulite “appears improved.” In addition, 29 (67.4%) strongly agreed, 13 (30.2%) agreed, and 1 (2.3%) disagreed with the statement “I feel there is good improvement” of their cellulite.
“Currently, we are evaluating the blinded assessors’ view of these patients and not just going with [findings from] the patient satisfaction survey, but I think these are encouraging results,” Dr. Tanzi said. “We found that 42 out of 43 patients said, ‘yes; I feel that there was good improvement of the area at 52 weeks.’ ”
Dr. Tanzi disclosed that she is a member of the speakers bureau for Eucerin. She is a member of the advisory board for Allergan, Endo Pharmaceuticals, Pulse Biosciences, Sciton, and Soliton. Soliton markets the RAP device.
One year after a single treatment of cellulite with the Rapid Acoustic Pulse (RAP) device, 42 out of 43 patients said that they felt good about the results, an interim analysis from a multicenter study showed.
“I think this speaks to the duration of improvement” associated with this treatment, lead study author Elizabeth L. Tanzi, MD, said during the annual conference of the American Society for Laser Medicine and Surgery.
The study is an extension of a prospective pivotal clinical trial that Dr. Tanzi first presented during late-breaking abstract session at the 2020 virtual annual meeting of the American Academy of Dermatology. For the trial, she and her colleagues at four sites evaluated the safety and effectiveness of the RAP device in 62 women who were treated with a single, rapid acoustic pulse treatment comprised of 1-2 minutes on each identified dimple or large ridge of cellulite. In February 2021, the Food and Drug Administration cleared the device for the short-term improvement in the appearance of cellulite.
“The high peak pressure and fast repetition rate of this device will exploit the viscoelastic tissue compared to other acoustic wave devices that are on the market,” said Dr. Tanzi, associate clinical professor of dermatology at George Washington University, Washington. “Those compressed pulses from electronic filtering and reflector shape eliminate cavitation, heat, and pain. So, what we see physically is fiber septa disruption, as well as other nonthermal physical effects.”
She and her colleagues used a specific photography and fixed lighting setup to record the treated areas at baseline, 12 weeks, and 52 weeks, and administered a patient satisfaction questionnaire at 12 and 52 weeks. Prior to treatment, the investigators marked the dimples and ridges intended for treatment. After placing a hydrogel dressing, it took 45-60 minutes to treat both buttocks and thighs with the RAP device. “It was completely noninvasive,” said Dr. Tanzi, who practices in Chevy Chase, Md. “There was no anesthesia used: no incisions and no needles.”
Among 57 patients who were evaluated at 12 weeks, the pain score on a scale of 0-10 was 2.4, while 61.5% strongly agreed and 35.9% agreed that their cellulite appeared improved. In addition, three blinded assessors were able to correctly identify the treated thigh 96% of the time and physician-graded Global Aesthetic Improvement Scale assessments showed 90% improvement of cellulite.
Follow-up analysis
For the current subject satisfaction analysis, the investigators evaluated results from 43 patients in the trial who were followed for at least 52 weeks (a mean of 60 weeks). Of the 43 patients, 30 (69.8%) strongly agreed and 13 (30.2%) agreed that their cellulite “appears improved.” In addition, 29 (67.4%) strongly agreed, 13 (30.2%) agreed, and 1 (2.3%) disagreed with the statement “I feel there is good improvement” of their cellulite.
“Currently, we are evaluating the blinded assessors’ view of these patients and not just going with [findings from] the patient satisfaction survey, but I think these are encouraging results,” Dr. Tanzi said. “We found that 42 out of 43 patients said, ‘yes; I feel that there was good improvement of the area at 52 weeks.’ ”
Dr. Tanzi disclosed that she is a member of the speakers bureau for Eucerin. She is a member of the advisory board for Allergan, Endo Pharmaceuticals, Pulse Biosciences, Sciton, and Soliton. Soliton markets the RAP device.
FROM ASLMS 2021
This is your chance to impact those in need with the CHEST Foundation
In 2020, the world was rocked by a global pandemic; our response was to provide COVID-19 community service grants to some of the most vulnerable populations. The CHEST Foundation, with support from donors and the Feldman Family Foundation, was able to provide $120,000 to support communities in need of essential items. Personal protective equipment, cleaning supplies, emergency food purchases, and more were purchased with these grants to aid communities disproportionately affected by the pandemic.
Without you, these grants would not have been possible. CHEST’s NetWorks worked all summer of 2020 to raise funds to make a tangible impact on at-risk communities in the wake of the pandemic. We’re counting on you again to help us raise money this year for more community service grants.
The NetWorks Challenge 2021 will fund community-based projects focused on health disparities and disproportionately underserved communities. Get ready to compete in the challenge to directly make an impact on those who could otherwise not afford access to health care.
This offering, dubbed Rita’s Fund, will award $2,500 to $10,000 to community-based projects providing resources to individuals to drastically change their quality of life. Medical equipment, transportation, and technology access aren’t available to all, but through this grant, they will be provided to those who need it most.
Rita’s Fund originated after hearing the story of Rita Castro during the virtual Listening Tour and our initiative to listen and identify barriers to trust, access, and equity in our most underserved communities. The CHEST Foundation was inspired by her story, as she was fighting a rapidly progressing lung condition with no support. Through donations she was able to receive the care she needed, and her diagnosis improved.
Your work during the NetWorks Challenge will help fund grants through Rita’s Fund and travel grants to attend this year’s CHEST Annual Meeting. We need your help to ensure individuals like Rita have access to better health and resources they can trust.
To learn more about this initiative and this year’s NetWorks Challenge, visit the CHEST Foundation’s website at https://foundation.chestnet.org.
In 2020, the world was rocked by a global pandemic; our response was to provide COVID-19 community service grants to some of the most vulnerable populations. The CHEST Foundation, with support from donors and the Feldman Family Foundation, was able to provide $120,000 to support communities in need of essential items. Personal protective equipment, cleaning supplies, emergency food purchases, and more were purchased with these grants to aid communities disproportionately affected by the pandemic.
Without you, these grants would not have been possible. CHEST’s NetWorks worked all summer of 2020 to raise funds to make a tangible impact on at-risk communities in the wake of the pandemic. We’re counting on you again to help us raise money this year for more community service grants.
The NetWorks Challenge 2021 will fund community-based projects focused on health disparities and disproportionately underserved communities. Get ready to compete in the challenge to directly make an impact on those who could otherwise not afford access to health care.
This offering, dubbed Rita’s Fund, will award $2,500 to $10,000 to community-based projects providing resources to individuals to drastically change their quality of life. Medical equipment, transportation, and technology access aren’t available to all, but through this grant, they will be provided to those who need it most.
Rita’s Fund originated after hearing the story of Rita Castro during the virtual Listening Tour and our initiative to listen and identify barriers to trust, access, and equity in our most underserved communities. The CHEST Foundation was inspired by her story, as she was fighting a rapidly progressing lung condition with no support. Through donations she was able to receive the care she needed, and her diagnosis improved.
Your work during the NetWorks Challenge will help fund grants through Rita’s Fund and travel grants to attend this year’s CHEST Annual Meeting. We need your help to ensure individuals like Rita have access to better health and resources they can trust.
To learn more about this initiative and this year’s NetWorks Challenge, visit the CHEST Foundation’s website at https://foundation.chestnet.org.
In 2020, the world was rocked by a global pandemic; our response was to provide COVID-19 community service grants to some of the most vulnerable populations. The CHEST Foundation, with support from donors and the Feldman Family Foundation, was able to provide $120,000 to support communities in need of essential items. Personal protective equipment, cleaning supplies, emergency food purchases, and more were purchased with these grants to aid communities disproportionately affected by the pandemic.
Without you, these grants would not have been possible. CHEST’s NetWorks worked all summer of 2020 to raise funds to make a tangible impact on at-risk communities in the wake of the pandemic. We’re counting on you again to help us raise money this year for more community service grants.
The NetWorks Challenge 2021 will fund community-based projects focused on health disparities and disproportionately underserved communities. Get ready to compete in the challenge to directly make an impact on those who could otherwise not afford access to health care.
This offering, dubbed Rita’s Fund, will award $2,500 to $10,000 to community-based projects providing resources to individuals to drastically change their quality of life. Medical equipment, transportation, and technology access aren’t available to all, but through this grant, they will be provided to those who need it most.
Rita’s Fund originated after hearing the story of Rita Castro during the virtual Listening Tour and our initiative to listen and identify barriers to trust, access, and equity in our most underserved communities. The CHEST Foundation was inspired by her story, as she was fighting a rapidly progressing lung condition with no support. Through donations she was able to receive the care she needed, and her diagnosis improved.
Your work during the NetWorks Challenge will help fund grants through Rita’s Fund and travel grants to attend this year’s CHEST Annual Meeting. We need your help to ensure individuals like Rita have access to better health and resources they can trust.
To learn more about this initiative and this year’s NetWorks Challenge, visit the CHEST Foundation’s website at https://foundation.chestnet.org.
In the previous year, 70% of oncologists reported sexual harassment
A new survey of sexual harassment among U.S. oncologists has found that 70% reported incidents from peers and/or supervisors in the previous 12 months.
The incidence was higher among women than men (80% vs. 56%), a difference that was statistically significant (P < .0001).
However, after experiencing sexual harassment from coworkers, men and women were alike in terms of reporting similarly negative outcomes in mental health, sense of safety, and turnover intentions (e.g., leaving or quitting).
“Our findings demonstrate that the impact of sexual harassment on both men and women is tangible and is not different,” said lead author Ishwaria Subbiah, MD, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston, during her presentation of the study on June 5 at the American Society of Clinical Oncology (ASCO) 2021. The meeting was held virtually because of the pandemic.
“The survey’s recall period [about harassment] was in the previous 12 months. The respondents weren’t reflecting on a lifetime of events,” Dr. Subbiah said in an interview. “That’s part of what makes the findings that much more sobering.”
The release of the survey results roughly coincided with a furor within oncology circles over details that have now come to light about Axel Grothey, MD, a high-profile medical oncologist who was forced out of the Mayo Clinic in Rochester, Minn., after having unethical sexual relations with mentees – only to move on to another major center with more mentees.
The new survey, which included 153 women and 118 men, was conducted in 2020.
Overall, 69% of respondents reported gender-based harassment, 17% reported unwanted sexual attention, and 3% reported sexual coercion from peers/supervisors. For the three types of sexual harassment, women reported higher rates of incidence; the greatest proportional disparity was in unwanted sexual attention (22% of women vs. 9% of men).
The types of sexual harassment are defined in a landmark 2018 report from the National Academies of Sciences, Engineering, and Medicine. Gender harassment is nonverbal or verbal behaviors that are hostile, objectifying, and excluding of or conveying second-class status about a gender. Unwanted sexual attention is advances, including touching, and seeking a sexual relationship despite discouragement. Sexual coercion involves seeking compliance with sexual demands by making job-related threats or promising job-related benefits.
The commonality in the three harassments is their being “unwanted,” Dr. Subbiah explained.
Another commonality is that “sexual harassment is a tool of power that one person yields over another,” commented Marina Stasenko, MD, a gynecologic oncologist at NYU Langone’s Perlmutter Cancer Center.
Dr. Stasenko led a 2018 study that found that 64% of U.S. gynecologic oncologists reported sexual harassment during training or practice, a much longer recall period than the 1 year in Dr. Subbiah’s study.
However, things may be changing regarding sexual harassment – at least in terms of victims speaking out, said Dr. Stasenko. Perhaps discussing personal experience “is becoming less taboo,” she told this news organization. “The media spotlight on sexual harassment within medicine has been bright [recently].”
That was borne out last week – a number of oncologists who had been harassed told their stories on Twitter in reaction to the report about Dr. Grothey at one of America’s top medical centers. Also, in another sign of the moment, an academic oncologist publicly said that rumors about Dr. Grothey were long-standing. “Heard from many colleagues that this behavior was known in the field and went on for years. Years,” tweeted Charu Aggarwal, MD, MPH, from the University of Pennsylvania, Philadelphia.
Other outcomes seem to make Dr. Grothey’s behavior at Mayo, which multiple oncologists said has occurred at every center, a watershed moment. Namely, he has been muted or dismissed by an array of organizations since the story broke.
ASCO disallowed Dr. Grothey from making presentations at the annual meeting (he was an author on 12 studies), the National Cancer Institute removed him from his position as co-chair of an influential steering committee that helps determine grant funding for research, and the OneOncology community care network dropped him as medical director of their research arm, as reported by The Cancer Letter. He was also removed from the OncoAlert Network, a global network of oncology professionals, and from the medical advisory board of Fight CRC, an advocacy group for patients with colorectal cancer, as reported by this news organization. His current employer, West Cancer Center, in Germantown, Tennessee, has also started an investigation.
In her presentation, Dr. Subbiah acknowledged a changing landscape, with “increasing attention in recent years” to sexual harassment thanks to the “broader cultural movements” of #metoo and #TIMESUP social media–based campaigns.
Another oncologist nodded to the recent news about Dr. Grothey at the Mayo Clinic and suggested Dr. Subbiah’s study was part of a historic struggle for equity for women. “Sadly, both timely and timeless,” tweeted medical oncologist Tatiana Prowell, MD, of Johns Hopkins University, Baltimore, about the new study.
Academia has a problem
To conduct their survey, Dr. Subbiah and her coinvestigators reached out to 1,000 randomly selected U.S. members of ASCO via the organization’s research survey pool, as well as through Twitter and Facebook. The invitation to participate described the survey as being about the “workplace experience of oncologists” and that it aimed to mitigate response bias.
Of the 271 survey respondents, 250 were oncologists in practice and 21 were residents/fellows. Nearly all were heterosexual (94%) and U.S. citizens (87%). A majority (53%) were White, 35% were Asian/Pacific Islander, and 11% were Black or Hispanic. Most (68%) were more than 5 years out from training.
Most of the respondents (62%) were from academia.
“There is a big problem of sexual harassment in academic medicine,” said Pamela Kunz, MD, of Yale Cancer Center, New Haven, Conn., who was asked for comment. Dr. Kunz left Stanford University in 2020 after 19 years, citing repeated harassment.
“The institutions tend to protect the brand rather than the victim. Perpetrators are often not disciplined and may leave an institution under cover of a resignation only to go on and receive a better leadership role at another institution,” she said in an interview.
A “revolution” is needed to address the problem, Dr. Kunz said, citing needs to routinely discuss the topic, systems to measure and track it, methods to hold perpetrators accountable, and meaningful educational opportunities.
Harassment from patients/families also tallied
The new survey also queried participants with regard to sexual harassment from patients and/or families, which was reported by 67% of women and 35% of men (P < .0001).
As with harassment from peers/supervisors, gender harassment was the most common form and was reported by significantly higher percentages of women.
And as with coworkers, sexual harassment from patients/families was also significantly associated with detriments to mental health, workplace safety, and turnover intentions.
Sexual harassment from “insiders” (P = .001) but not patients (P = .55) was significantly associated with a decrease in a fourth metric in the study – job satisfaction.
“The goal of medicine and oncology is ‘ultimately to ease suffering,’” Dr. Subbiah said. That holds true for workplace wellness, including addressing harassment. “There should be no hesitation to go there and look at what is truly impacting the workplace,” she said.
“This is a difficult topic,” Dr. Subbiah acknowledged, adding that “the findings are sobering and merit open, global conversation among all oncology stakeholders.”
The study authors, Dr. Ganz, and Dr. Stasenko have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new survey of sexual harassment among U.S. oncologists has found that 70% reported incidents from peers and/or supervisors in the previous 12 months.
The incidence was higher among women than men (80% vs. 56%), a difference that was statistically significant (P < .0001).
However, after experiencing sexual harassment from coworkers, men and women were alike in terms of reporting similarly negative outcomes in mental health, sense of safety, and turnover intentions (e.g., leaving or quitting).
“Our findings demonstrate that the impact of sexual harassment on both men and women is tangible and is not different,” said lead author Ishwaria Subbiah, MD, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston, during her presentation of the study on June 5 at the American Society of Clinical Oncology (ASCO) 2021. The meeting was held virtually because of the pandemic.
“The survey’s recall period [about harassment] was in the previous 12 months. The respondents weren’t reflecting on a lifetime of events,” Dr. Subbiah said in an interview. “That’s part of what makes the findings that much more sobering.”
The release of the survey results roughly coincided with a furor within oncology circles over details that have now come to light about Axel Grothey, MD, a high-profile medical oncologist who was forced out of the Mayo Clinic in Rochester, Minn., after having unethical sexual relations with mentees – only to move on to another major center with more mentees.
The new survey, which included 153 women and 118 men, was conducted in 2020.
Overall, 69% of respondents reported gender-based harassment, 17% reported unwanted sexual attention, and 3% reported sexual coercion from peers/supervisors. For the three types of sexual harassment, women reported higher rates of incidence; the greatest proportional disparity was in unwanted sexual attention (22% of women vs. 9% of men).
The types of sexual harassment are defined in a landmark 2018 report from the National Academies of Sciences, Engineering, and Medicine. Gender harassment is nonverbal or verbal behaviors that are hostile, objectifying, and excluding of or conveying second-class status about a gender. Unwanted sexual attention is advances, including touching, and seeking a sexual relationship despite discouragement. Sexual coercion involves seeking compliance with sexual demands by making job-related threats or promising job-related benefits.
The commonality in the three harassments is their being “unwanted,” Dr. Subbiah explained.
Another commonality is that “sexual harassment is a tool of power that one person yields over another,” commented Marina Stasenko, MD, a gynecologic oncologist at NYU Langone’s Perlmutter Cancer Center.
Dr. Stasenko led a 2018 study that found that 64% of U.S. gynecologic oncologists reported sexual harassment during training or practice, a much longer recall period than the 1 year in Dr. Subbiah’s study.
However, things may be changing regarding sexual harassment – at least in terms of victims speaking out, said Dr. Stasenko. Perhaps discussing personal experience “is becoming less taboo,” she told this news organization. “The media spotlight on sexual harassment within medicine has been bright [recently].”
That was borne out last week – a number of oncologists who had been harassed told their stories on Twitter in reaction to the report about Dr. Grothey at one of America’s top medical centers. Also, in another sign of the moment, an academic oncologist publicly said that rumors about Dr. Grothey were long-standing. “Heard from many colleagues that this behavior was known in the field and went on for years. Years,” tweeted Charu Aggarwal, MD, MPH, from the University of Pennsylvania, Philadelphia.
Other outcomes seem to make Dr. Grothey’s behavior at Mayo, which multiple oncologists said has occurred at every center, a watershed moment. Namely, he has been muted or dismissed by an array of organizations since the story broke.
ASCO disallowed Dr. Grothey from making presentations at the annual meeting (he was an author on 12 studies), the National Cancer Institute removed him from his position as co-chair of an influential steering committee that helps determine grant funding for research, and the OneOncology community care network dropped him as medical director of their research arm, as reported by The Cancer Letter. He was also removed from the OncoAlert Network, a global network of oncology professionals, and from the medical advisory board of Fight CRC, an advocacy group for patients with colorectal cancer, as reported by this news organization. His current employer, West Cancer Center, in Germantown, Tennessee, has also started an investigation.
In her presentation, Dr. Subbiah acknowledged a changing landscape, with “increasing attention in recent years” to sexual harassment thanks to the “broader cultural movements” of #metoo and #TIMESUP social media–based campaigns.
Another oncologist nodded to the recent news about Dr. Grothey at the Mayo Clinic and suggested Dr. Subbiah’s study was part of a historic struggle for equity for women. “Sadly, both timely and timeless,” tweeted medical oncologist Tatiana Prowell, MD, of Johns Hopkins University, Baltimore, about the new study.
Academia has a problem
To conduct their survey, Dr. Subbiah and her coinvestigators reached out to 1,000 randomly selected U.S. members of ASCO via the organization’s research survey pool, as well as through Twitter and Facebook. The invitation to participate described the survey as being about the “workplace experience of oncologists” and that it aimed to mitigate response bias.
Of the 271 survey respondents, 250 were oncologists in practice and 21 were residents/fellows. Nearly all were heterosexual (94%) and U.S. citizens (87%). A majority (53%) were White, 35% were Asian/Pacific Islander, and 11% were Black or Hispanic. Most (68%) were more than 5 years out from training.
Most of the respondents (62%) were from academia.
“There is a big problem of sexual harassment in academic medicine,” said Pamela Kunz, MD, of Yale Cancer Center, New Haven, Conn., who was asked for comment. Dr. Kunz left Stanford University in 2020 after 19 years, citing repeated harassment.
“The institutions tend to protect the brand rather than the victim. Perpetrators are often not disciplined and may leave an institution under cover of a resignation only to go on and receive a better leadership role at another institution,” she said in an interview.
A “revolution” is needed to address the problem, Dr. Kunz said, citing needs to routinely discuss the topic, systems to measure and track it, methods to hold perpetrators accountable, and meaningful educational opportunities.
Harassment from patients/families also tallied
The new survey also queried participants with regard to sexual harassment from patients and/or families, which was reported by 67% of women and 35% of men (P < .0001).
As with harassment from peers/supervisors, gender harassment was the most common form and was reported by significantly higher percentages of women.
And as with coworkers, sexual harassment from patients/families was also significantly associated with detriments to mental health, workplace safety, and turnover intentions.
Sexual harassment from “insiders” (P = .001) but not patients (P = .55) was significantly associated with a decrease in a fourth metric in the study – job satisfaction.
“The goal of medicine and oncology is ‘ultimately to ease suffering,’” Dr. Subbiah said. That holds true for workplace wellness, including addressing harassment. “There should be no hesitation to go there and look at what is truly impacting the workplace,” she said.
“This is a difficult topic,” Dr. Subbiah acknowledged, adding that “the findings are sobering and merit open, global conversation among all oncology stakeholders.”
The study authors, Dr. Ganz, and Dr. Stasenko have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new survey of sexual harassment among U.S. oncologists has found that 70% reported incidents from peers and/or supervisors in the previous 12 months.
The incidence was higher among women than men (80% vs. 56%), a difference that was statistically significant (P < .0001).
However, after experiencing sexual harassment from coworkers, men and women were alike in terms of reporting similarly negative outcomes in mental health, sense of safety, and turnover intentions (e.g., leaving or quitting).
“Our findings demonstrate that the impact of sexual harassment on both men and women is tangible and is not different,” said lead author Ishwaria Subbiah, MD, a medical oncologist at the University of Texas MD Anderson Cancer Center, Houston, during her presentation of the study on June 5 at the American Society of Clinical Oncology (ASCO) 2021. The meeting was held virtually because of the pandemic.
“The survey’s recall period [about harassment] was in the previous 12 months. The respondents weren’t reflecting on a lifetime of events,” Dr. Subbiah said in an interview. “That’s part of what makes the findings that much more sobering.”
The release of the survey results roughly coincided with a furor within oncology circles over details that have now come to light about Axel Grothey, MD, a high-profile medical oncologist who was forced out of the Mayo Clinic in Rochester, Minn., after having unethical sexual relations with mentees – only to move on to another major center with more mentees.
The new survey, which included 153 women and 118 men, was conducted in 2020.
Overall, 69% of respondents reported gender-based harassment, 17% reported unwanted sexual attention, and 3% reported sexual coercion from peers/supervisors. For the three types of sexual harassment, women reported higher rates of incidence; the greatest proportional disparity was in unwanted sexual attention (22% of women vs. 9% of men).
The types of sexual harassment are defined in a landmark 2018 report from the National Academies of Sciences, Engineering, and Medicine. Gender harassment is nonverbal or verbal behaviors that are hostile, objectifying, and excluding of or conveying second-class status about a gender. Unwanted sexual attention is advances, including touching, and seeking a sexual relationship despite discouragement. Sexual coercion involves seeking compliance with sexual demands by making job-related threats or promising job-related benefits.
The commonality in the three harassments is their being “unwanted,” Dr. Subbiah explained.
Another commonality is that “sexual harassment is a tool of power that one person yields over another,” commented Marina Stasenko, MD, a gynecologic oncologist at NYU Langone’s Perlmutter Cancer Center.
Dr. Stasenko led a 2018 study that found that 64% of U.S. gynecologic oncologists reported sexual harassment during training or practice, a much longer recall period than the 1 year in Dr. Subbiah’s study.
However, things may be changing regarding sexual harassment – at least in terms of victims speaking out, said Dr. Stasenko. Perhaps discussing personal experience “is becoming less taboo,” she told this news organization. “The media spotlight on sexual harassment within medicine has been bright [recently].”
That was borne out last week – a number of oncologists who had been harassed told their stories on Twitter in reaction to the report about Dr. Grothey at one of America’s top medical centers. Also, in another sign of the moment, an academic oncologist publicly said that rumors about Dr. Grothey were long-standing. “Heard from many colleagues that this behavior was known in the field and went on for years. Years,” tweeted Charu Aggarwal, MD, MPH, from the University of Pennsylvania, Philadelphia.
Other outcomes seem to make Dr. Grothey’s behavior at Mayo, which multiple oncologists said has occurred at every center, a watershed moment. Namely, he has been muted or dismissed by an array of organizations since the story broke.
ASCO disallowed Dr. Grothey from making presentations at the annual meeting (he was an author on 12 studies), the National Cancer Institute removed him from his position as co-chair of an influential steering committee that helps determine grant funding for research, and the OneOncology community care network dropped him as medical director of their research arm, as reported by The Cancer Letter. He was also removed from the OncoAlert Network, a global network of oncology professionals, and from the medical advisory board of Fight CRC, an advocacy group for patients with colorectal cancer, as reported by this news organization. His current employer, West Cancer Center, in Germantown, Tennessee, has also started an investigation.
In her presentation, Dr. Subbiah acknowledged a changing landscape, with “increasing attention in recent years” to sexual harassment thanks to the “broader cultural movements” of #metoo and #TIMESUP social media–based campaigns.
Another oncologist nodded to the recent news about Dr. Grothey at the Mayo Clinic and suggested Dr. Subbiah’s study was part of a historic struggle for equity for women. “Sadly, both timely and timeless,” tweeted medical oncologist Tatiana Prowell, MD, of Johns Hopkins University, Baltimore, about the new study.
Academia has a problem
To conduct their survey, Dr. Subbiah and her coinvestigators reached out to 1,000 randomly selected U.S. members of ASCO via the organization’s research survey pool, as well as through Twitter and Facebook. The invitation to participate described the survey as being about the “workplace experience of oncologists” and that it aimed to mitigate response bias.
Of the 271 survey respondents, 250 were oncologists in practice and 21 were residents/fellows. Nearly all were heterosexual (94%) and U.S. citizens (87%). A majority (53%) were White, 35% were Asian/Pacific Islander, and 11% were Black or Hispanic. Most (68%) were more than 5 years out from training.
Most of the respondents (62%) were from academia.
“There is a big problem of sexual harassment in academic medicine,” said Pamela Kunz, MD, of Yale Cancer Center, New Haven, Conn., who was asked for comment. Dr. Kunz left Stanford University in 2020 after 19 years, citing repeated harassment.
“The institutions tend to protect the brand rather than the victim. Perpetrators are often not disciplined and may leave an institution under cover of a resignation only to go on and receive a better leadership role at another institution,” she said in an interview.
A “revolution” is needed to address the problem, Dr. Kunz said, citing needs to routinely discuss the topic, systems to measure and track it, methods to hold perpetrators accountable, and meaningful educational opportunities.
Harassment from patients/families also tallied
The new survey also queried participants with regard to sexual harassment from patients and/or families, which was reported by 67% of women and 35% of men (P < .0001).
As with harassment from peers/supervisors, gender harassment was the most common form and was reported by significantly higher percentages of women.
And as with coworkers, sexual harassment from patients/families was also significantly associated with detriments to mental health, workplace safety, and turnover intentions.
Sexual harassment from “insiders” (P = .001) but not patients (P = .55) was significantly associated with a decrease in a fourth metric in the study – job satisfaction.
“The goal of medicine and oncology is ‘ultimately to ease suffering,’” Dr. Subbiah said. That holds true for workplace wellness, including addressing harassment. “There should be no hesitation to go there and look at what is truly impacting the workplace,” she said.
“This is a difficult topic,” Dr. Subbiah acknowledged, adding that “the findings are sobering and merit open, global conversation among all oncology stakeholders.”
The study authors, Dr. Ganz, and Dr. Stasenko have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Music and the human brain
Music has to be one of humanity’s most unique traits, and, at the same time, one of neurology’s greatest mysteries.
Where did it come from, and why?
When it started, we can only guess. The first known musical instrument is a flute carved from bear bone, made 67,000 years ago, but music is certainly older. The first instruments were probably clapped hands, then rocks and sticks.
Tens of thousands of cultures have developed over the course of human history. And, to date, not a single one is known that didn’t have music.
It takes energy to create music, too: to make and play instruments, think of songs, sing ... So at some point having music became an evolutionary advantage of some sort (one can imagine Bill and Ted saying “Dude, chicks dig it”) or it wouldn’t have lasted. Then, as people spread out, music forms got mixed and matched among cultures. Always changing, never leaving, and now somehow woven into the DNA of our brains.
The physics principles behind music are limited and simple: percussion, a vibrating string, air movement in a tube ... But from such simple things the human brain has adapted thousands of natural, and now synthetic, objects, to create an endless variety of unique sounds.
There are plenty of articles out there about how music can be relaxing or stimulating, capable of distracting you or helping you concentrate. Music can help you forget a bad day or remember a good one. They talk about PET scans and cortical activation and many other interesting things that show the effect of music on the remarkable human brain.
But at some level it doesn’t matter to me. I don’t try to understand music any more than I try to understand my dogs. I just know I couldn’t live without either. I’m not alone. Look around you: How many people on the train, or plane, or in the gym have earbuds on?
I have iTunes on my office computer, with roughly 5,000 songs covering the majority of genres from classical to rock. It’s the first program I switch on early each morning when I start the day. It gets me focused on the work at hand, and adds an enjoyable element to the day.
I’m not a musician. I took a few guitar lessons as a kid, but never really learned it. I used to joke that the only instrument I could play was the stereo (now I guess it’s iTunes). Coming from a maternal line of excellent musicians, it’s embarrassing to admit my lack of talent. But my inability to perform it myself doesn’t keep me from enjoying it.
There is no better example of the remarkable human memory than its ability to instantly recall the lyrics of songs you haven’t heard for 20, 30, 40, or more years. A few notes and it’s like you heard them yesterday. At this point, almost 30 years since my medical school graduation, I’ve likely forgotten a large portion of what I learned there. But 70s or 80s pop from my youth? Still there, and immediately recalled.
We process music everywhere – at stores, in elevators, in the car – without realizing it, like driving down the street and automatically reading signs as we pass them. But no matter where it is in our level of realization at the time, it’s a key part of our everyday lives.
Another marvel of the remarkable human brain.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Music has to be one of humanity’s most unique traits, and, at the same time, one of neurology’s greatest mysteries.
Where did it come from, and why?
When it started, we can only guess. The first known musical instrument is a flute carved from bear bone, made 67,000 years ago, but music is certainly older. The first instruments were probably clapped hands, then rocks and sticks.
Tens of thousands of cultures have developed over the course of human history. And, to date, not a single one is known that didn’t have music.
It takes energy to create music, too: to make and play instruments, think of songs, sing ... So at some point having music became an evolutionary advantage of some sort (one can imagine Bill and Ted saying “Dude, chicks dig it”) or it wouldn’t have lasted. Then, as people spread out, music forms got mixed and matched among cultures. Always changing, never leaving, and now somehow woven into the DNA of our brains.
The physics principles behind music are limited and simple: percussion, a vibrating string, air movement in a tube ... But from such simple things the human brain has adapted thousands of natural, and now synthetic, objects, to create an endless variety of unique sounds.
There are plenty of articles out there about how music can be relaxing or stimulating, capable of distracting you or helping you concentrate. Music can help you forget a bad day or remember a good one. They talk about PET scans and cortical activation and many other interesting things that show the effect of music on the remarkable human brain.
But at some level it doesn’t matter to me. I don’t try to understand music any more than I try to understand my dogs. I just know I couldn’t live without either. I’m not alone. Look around you: How many people on the train, or plane, or in the gym have earbuds on?
I have iTunes on my office computer, with roughly 5,000 songs covering the majority of genres from classical to rock. It’s the first program I switch on early each morning when I start the day. It gets me focused on the work at hand, and adds an enjoyable element to the day.
I’m not a musician. I took a few guitar lessons as a kid, but never really learned it. I used to joke that the only instrument I could play was the stereo (now I guess it’s iTunes). Coming from a maternal line of excellent musicians, it’s embarrassing to admit my lack of talent. But my inability to perform it myself doesn’t keep me from enjoying it.
There is no better example of the remarkable human memory than its ability to instantly recall the lyrics of songs you haven’t heard for 20, 30, 40, or more years. A few notes and it’s like you heard them yesterday. At this point, almost 30 years since my medical school graduation, I’ve likely forgotten a large portion of what I learned there. But 70s or 80s pop from my youth? Still there, and immediately recalled.
We process music everywhere – at stores, in elevators, in the car – without realizing it, like driving down the street and automatically reading signs as we pass them. But no matter where it is in our level of realization at the time, it’s a key part of our everyday lives.
Another marvel of the remarkable human brain.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Music has to be one of humanity’s most unique traits, and, at the same time, one of neurology’s greatest mysteries.
Where did it come from, and why?
When it started, we can only guess. The first known musical instrument is a flute carved from bear bone, made 67,000 years ago, but music is certainly older. The first instruments were probably clapped hands, then rocks and sticks.
Tens of thousands of cultures have developed over the course of human history. And, to date, not a single one is known that didn’t have music.
It takes energy to create music, too: to make and play instruments, think of songs, sing ... So at some point having music became an evolutionary advantage of some sort (one can imagine Bill and Ted saying “Dude, chicks dig it”) or it wouldn’t have lasted. Then, as people spread out, music forms got mixed and matched among cultures. Always changing, never leaving, and now somehow woven into the DNA of our brains.
The physics principles behind music are limited and simple: percussion, a vibrating string, air movement in a tube ... But from such simple things the human brain has adapted thousands of natural, and now synthetic, objects, to create an endless variety of unique sounds.
There are plenty of articles out there about how music can be relaxing or stimulating, capable of distracting you or helping you concentrate. Music can help you forget a bad day or remember a good one. They talk about PET scans and cortical activation and many other interesting things that show the effect of music on the remarkable human brain.
But at some level it doesn’t matter to me. I don’t try to understand music any more than I try to understand my dogs. I just know I couldn’t live without either. I’m not alone. Look around you: How many people on the train, or plane, or in the gym have earbuds on?
I have iTunes on my office computer, with roughly 5,000 songs covering the majority of genres from classical to rock. It’s the first program I switch on early each morning when I start the day. It gets me focused on the work at hand, and adds an enjoyable element to the day.
I’m not a musician. I took a few guitar lessons as a kid, but never really learned it. I used to joke that the only instrument I could play was the stereo (now I guess it’s iTunes). Coming from a maternal line of excellent musicians, it’s embarrassing to admit my lack of talent. But my inability to perform it myself doesn’t keep me from enjoying it.
There is no better example of the remarkable human memory than its ability to instantly recall the lyrics of songs you haven’t heard for 20, 30, 40, or more years. A few notes and it’s like you heard them yesterday. At this point, almost 30 years since my medical school graduation, I’ve likely forgotten a large portion of what I learned there. But 70s or 80s pop from my youth? Still there, and immediately recalled.
We process music everywhere – at stores, in elevators, in the car – without realizing it, like driving down the street and automatically reading signs as we pass them. But no matter where it is in our level of realization at the time, it’s a key part of our everyday lives.
Another marvel of the remarkable human brain.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Red meat intake tied to higher coronary heart disease risk
Increased intake of meat was linked to the risk of coronary heart disease, and substituting plant protein for red or processed meat appeared to reduce that risk, in a study from pooled cohorts totaling more than a million persons.
“We know that red and processed meat intake has been associated with higher risks of fatal coronary heart disease,” said Laila Al-Shaar, PhD, of Penn State University, Hershey. However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk, she said.
In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, Dr. Al-Shaar and colleagues reviewed individual-level data from the Pooling Project of Prospective Studies of Diet and Cancer, which included 16 prospective cohorts totaling 1,364,211 participants. The average age of the participants was 57 years, and 40% were men. Individuals with a history of cancer or cardiovascular disease were excluded. The participants were followed for 7-32 years. Diet was assessed in each cohort using baselines questionnaires, and cases were identified through medical records.
Total red meat included processed meat and unprocessed red meat; animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; and plant protein sources included nuts and beans.
The researchers identified 51,176 fatal CHD cases during the study period. After controlling for dietary and nondietary factors, they found that an increase of 100 g per day of total red meat intake was associated with a 7% increased risk of fatal coronary heart disease (relative risk, 1.07).
However, substituting 200 calories (kcal) per day from nuts, low- and high-fat dairy products, and poultry for 200 calories per day from total red meat was associated with a 6%-14% lower risk of fatal CHD, Dr. Al-Shaar added at the meeting sponsored by the American Heart Association.
These associations were stronger when substituting the alternative protein sources for processed meat, especially among women; risk was reduced by 17%-24%, on the basis of 14,888 cases.
The researchers also found that substituting 200 calories per day from eggs for 200 calories per day for total red meat and unprocessed red meat was associated with 8% and 14% higher risk of fatal CHD, respectively; but this substitution of eggs for processed meat was not significant (4%).
“When we did the association by gender, the results were even stronger in women,” said Dr. Al-Shaar. However, “these are very preliminary results” that should be interpreted with caution, and more analysis is needed, she said. “We are planning to include other cohorts with other protein sources such as soy protein,” she noted. However, the results provide additional evidence that consumption of red and processed meat contributes to an increased risk of coronary heart disease, and that substituting some red and processed meat with nuts, dairy products, or poultry may reduce this risk, she concluded.
Women especially benefit from red meat reduction
The study is important because of the continuing interest in various sources of dietary protein intake, Linda Van Horn, PhD, RD, of Northwestern University, Chicago, said in an interview.
“The investigators studied associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD,” she said.
The researchers found that swapping as little as 200 calories per day of total red meat for nuts, low- or high-fat dairy products, or poultry were associated with a 6%-14% reduced risk of fatal CHD, said Dr. Van Horn. “Alternatively, if those 200 calories per day for red meat were substituted with eggs, they saw as much as 14% higher risk of fatal CHD,” she noted.
The message for both consumers and clinicians is that the findings from this large study support recommendations for plant-based and lean animal sources of protein instead of red and processed meat or eggs, as these sources “offer significantly lower risk for CHD mortality,” Dr. Van Horn said. “This may be especially true for women, but the total population is likely to benefit from this approach,” she said.
Additional research is needed, Dr. Van Horn emphasized. “Prospective lifetime data, starting in utero and over the life course, are needed to better establish recommended dietary patterns at every age and among all ethnicities and diverse socioeconomic groups,” she said.
Dr. Al-Shaar had no financial conflicts to disclose. Dr. Van Horn had no financial conflicts to disclose.
Increased intake of meat was linked to the risk of coronary heart disease, and substituting plant protein for red or processed meat appeared to reduce that risk, in a study from pooled cohorts totaling more than a million persons.
“We know that red and processed meat intake has been associated with higher risks of fatal coronary heart disease,” said Laila Al-Shaar, PhD, of Penn State University, Hershey. However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk, she said.
In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, Dr. Al-Shaar and colleagues reviewed individual-level data from the Pooling Project of Prospective Studies of Diet and Cancer, which included 16 prospective cohorts totaling 1,364,211 participants. The average age of the participants was 57 years, and 40% were men. Individuals with a history of cancer or cardiovascular disease were excluded. The participants were followed for 7-32 years. Diet was assessed in each cohort using baselines questionnaires, and cases were identified through medical records.
Total red meat included processed meat and unprocessed red meat; animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; and plant protein sources included nuts and beans.
The researchers identified 51,176 fatal CHD cases during the study period. After controlling for dietary and nondietary factors, they found that an increase of 100 g per day of total red meat intake was associated with a 7% increased risk of fatal coronary heart disease (relative risk, 1.07).
However, substituting 200 calories (kcal) per day from nuts, low- and high-fat dairy products, and poultry for 200 calories per day from total red meat was associated with a 6%-14% lower risk of fatal CHD, Dr. Al-Shaar added at the meeting sponsored by the American Heart Association.
These associations were stronger when substituting the alternative protein sources for processed meat, especially among women; risk was reduced by 17%-24%, on the basis of 14,888 cases.
The researchers also found that substituting 200 calories per day from eggs for 200 calories per day for total red meat and unprocessed red meat was associated with 8% and 14% higher risk of fatal CHD, respectively; but this substitution of eggs for processed meat was not significant (4%).
“When we did the association by gender, the results were even stronger in women,” said Dr. Al-Shaar. However, “these are very preliminary results” that should be interpreted with caution, and more analysis is needed, she said. “We are planning to include other cohorts with other protein sources such as soy protein,” she noted. However, the results provide additional evidence that consumption of red and processed meat contributes to an increased risk of coronary heart disease, and that substituting some red and processed meat with nuts, dairy products, or poultry may reduce this risk, she concluded.
Women especially benefit from red meat reduction
The study is important because of the continuing interest in various sources of dietary protein intake, Linda Van Horn, PhD, RD, of Northwestern University, Chicago, said in an interview.
“The investigators studied associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD,” she said.
The researchers found that swapping as little as 200 calories per day of total red meat for nuts, low- or high-fat dairy products, or poultry were associated with a 6%-14% reduced risk of fatal CHD, said Dr. Van Horn. “Alternatively, if those 200 calories per day for red meat were substituted with eggs, they saw as much as 14% higher risk of fatal CHD,” she noted.
The message for both consumers and clinicians is that the findings from this large study support recommendations for plant-based and lean animal sources of protein instead of red and processed meat or eggs, as these sources “offer significantly lower risk for CHD mortality,” Dr. Van Horn said. “This may be especially true for women, but the total population is likely to benefit from this approach,” she said.
Additional research is needed, Dr. Van Horn emphasized. “Prospective lifetime data, starting in utero and over the life course, are needed to better establish recommended dietary patterns at every age and among all ethnicities and diverse socioeconomic groups,” she said.
Dr. Al-Shaar had no financial conflicts to disclose. Dr. Van Horn had no financial conflicts to disclose.
Increased intake of meat was linked to the risk of coronary heart disease, and substituting plant protein for red or processed meat appeared to reduce that risk, in a study from pooled cohorts totaling more than a million persons.
“We know that red and processed meat intake has been associated with higher risks of fatal coronary heart disease,” said Laila Al-Shaar, PhD, of Penn State University, Hershey. However, very few studies have evaluated substitution of alternative protein sources for red and processed meat in relation to fatal CHD risk, she said.
In a study presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, Dr. Al-Shaar and colleagues reviewed individual-level data from the Pooling Project of Prospective Studies of Diet and Cancer, which included 16 prospective cohorts totaling 1,364,211 participants. The average age of the participants was 57 years, and 40% were men. Individuals with a history of cancer or cardiovascular disease were excluded. The participants were followed for 7-32 years. Diet was assessed in each cohort using baselines questionnaires, and cases were identified through medical records.
Total red meat included processed meat and unprocessed red meat; animal protein sources included seafood, poultry, eggs, and low- and high-fat dairy products; and plant protein sources included nuts and beans.
The researchers identified 51,176 fatal CHD cases during the study period. After controlling for dietary and nondietary factors, they found that an increase of 100 g per day of total red meat intake was associated with a 7% increased risk of fatal coronary heart disease (relative risk, 1.07).
However, substituting 200 calories (kcal) per day from nuts, low- and high-fat dairy products, and poultry for 200 calories per day from total red meat was associated with a 6%-14% lower risk of fatal CHD, Dr. Al-Shaar added at the meeting sponsored by the American Heart Association.
These associations were stronger when substituting the alternative protein sources for processed meat, especially among women; risk was reduced by 17%-24%, on the basis of 14,888 cases.
The researchers also found that substituting 200 calories per day from eggs for 200 calories per day for total red meat and unprocessed red meat was associated with 8% and 14% higher risk of fatal CHD, respectively; but this substitution of eggs for processed meat was not significant (4%).
“When we did the association by gender, the results were even stronger in women,” said Dr. Al-Shaar. However, “these are very preliminary results” that should be interpreted with caution, and more analysis is needed, she said. “We are planning to include other cohorts with other protein sources such as soy protein,” she noted. However, the results provide additional evidence that consumption of red and processed meat contributes to an increased risk of coronary heart disease, and that substituting some red and processed meat with nuts, dairy products, or poultry may reduce this risk, she concluded.
Women especially benefit from red meat reduction
The study is important because of the continuing interest in various sources of dietary protein intake, Linda Van Horn, PhD, RD, of Northwestern University, Chicago, said in an interview.
“The investigators studied associations of substituting other animal and plant protein sources for total red meat, unprocessed red meat, and processed meat in relation to risk of fatal CHD,” she said.
The researchers found that swapping as little as 200 calories per day of total red meat for nuts, low- or high-fat dairy products, or poultry were associated with a 6%-14% reduced risk of fatal CHD, said Dr. Van Horn. “Alternatively, if those 200 calories per day for red meat were substituted with eggs, they saw as much as 14% higher risk of fatal CHD,” she noted.
The message for both consumers and clinicians is that the findings from this large study support recommendations for plant-based and lean animal sources of protein instead of red and processed meat or eggs, as these sources “offer significantly lower risk for CHD mortality,” Dr. Van Horn said. “This may be especially true for women, but the total population is likely to benefit from this approach,” she said.
Additional research is needed, Dr. Van Horn emphasized. “Prospective lifetime data, starting in utero and over the life course, are needed to better establish recommended dietary patterns at every age and among all ethnicities and diverse socioeconomic groups,” she said.
Dr. Al-Shaar had no financial conflicts to disclose. Dr. Van Horn had no financial conflicts to disclose.
FROM EPI/LIFESTYLE 2021
Surgical outcomes favor addition of nivolumab to neoadjuvant chemo in resectable lung cancers
The addition of nivolumab to neoadjuvant chemotherapy did not impede the feasibility or timing of surgery in patients with resectable lung cancer, according to results from the phase 3 CheckMate 816 trial.
Adding nivolumab to chemotherapy was tolerable and did not increase the rate of surgical complications, investigator Jonathan Spicer, FRCPC, MD, PhD, of McGill University, Montreal, said in his presentation at the annual meeting of the American Society of Clinical Oncology.
His presentation comes about 2 months after the reporting of primary endpoint results of CheckMate 816 (NCT02998528). CheckMate 816 demonstrated that adding nivolumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) in patients with resectable non–small cell lung cancer (NSCLC), according to results presented earlier at the American Association for Cancer Research annual meeting.
“The safety and surgical outcome data reported thus far from CheckMate 816, along with significant improvement in pathological complete response, support nivolumab in combination with chemotherapy as an attractive neoadjuvant option for patients with resectable NSCLC,” said Dr. Spicer (Abstract 8503).
Building on previous experience
The CheckMate 816 study builds on extensive experience in advanced NSCLC that has consistently shown better outcomes, including overall survival, with combinations of chemotherapy and immuno-oncology (IO) agents, compared to chemotherapy alone, said discussant Valerie W. Rusch, MD, of Memorial Sloan Kettering Cancer Center in New York.
Dr. Rusch called out “salient and interesting results” regarding surgical management in CheckMate 816, including a lower rate of surgery cancellations and shorter surgical duration in the chemotherapy-plus-IO arm, compared to the chemotherapy-alone arm.
Furthermore, fewer patients required a pneumonectomy and more patients had a complete resection in the chemotherapy-plus-IO arm, compared to chemotherapy alone, she noted.
“These excellent surgical results, along with the data previously presented at AACR regarding the primary endpoint, help to establish a new standard of neoadjuvant care,” Dr. Rusch said in her presentation.
Study details
CheckMate 816 included 358 patients with newly diagnosed, resectable, stage IB-IIIA NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no known EGFR mutations or ALK alterations. Patients were randomized to receive nivolumab and platinum-doublet chemotherapy (nivolumab/chemotherapy) or chemotherapy alone every 3 weeks, with surgery to be performed within 6 weeks of the last dose of neoadjuvant treatment.
The median age of patients was 64 years in the nivolumab/chemotherapy arm and 65 years in the chemotherapy-alone arm. About one-third of patients had ECOG performance status of one, and about half had squamous tumor histology, Dr. Spicer said in his report. Almost two-thirds of patients had stage IIIA disease.
In the study results previously presented at the AACR meeting, both pCR and major pathologic response were significantly better following neoadjuvant chemotherapy and IO treatment, compared to chemotherapy alone.
In the intention-to-treat analysis, 24.0% of patients treated with nivolumab/chemotherapy achieved a pCR, compared to 2.2% in the chemotherapy arm, amounting to an approximate 12-fold increase in pCR, Dr. Spicer said. Similarly, the rate of major pathologic response in the intention-to-treat analysis was 36.9% and 8.9% for the nivolumab/chemotherapy and chemotherapy arms, respectively.
Surgical results
In his ASCO presentation, Dr. Spicer reported that definitive surgery was canceled in 16% of patients in the nivolumab/chemotherapy arm, and 21% of the chemotherapy arm. Reasons for surgery cancellation generally included patients declining surgery, unresectable disease, and poor lung function. “Cancellation of surgery due to neoadjuvant therapy toxicity was rare,” Dr. Spicer said in his presentation.
Among patients who did proceed to surgery, the median duration of the procedure was 184 minutes in the nivolumab/chemotherapy arm and 217 minutes in the chemotherapy arm. That half-hour difference in favor of the combination arm suggests that the complexity of surgery was not increased by the addition of nivolumab, Dr. Spicer said.
Median time to surgery was about 5 weeks in both arms, which was “well within accepted standards for a neoadjuvant therapeutic approach,” Dr. Spicer said. Most delays beyond 6 weeks were due to administrative issues, and occurred in similar proportions (21% of the nivolumab/chemotherapy arm and 18% of the chemotherapy arm).
The addition of nivolumab to chemotherapy improved pCR rates regardless of baseline stage of disease, according to Dr. Spicer. Furthermore, the depth of pathological regression in the primary tumor was “dramatically different” across stage groupings, he said. Median residual viable tumor percentage in stage IB/II patients was 28% for nivolumab/chemotherapy and 79% for chemotherapy, and in stage IIIA patients, it was 8% for nivolumab/chemotherapy and 70% for chemotherapy.
Overall, thoracotomy was the most frequent surgical approach in this international phase 3 trial, Dr. Spicer said. However, among patients with stage IIIA disease, minimally invasive approaches were used 30% of the time in the nivolumab/chemotherapy arm and 19% in the chemotherapy arm. Conversely, the rate of conversion from a minimally invasive to open approach in patients with stage IIIA disease was 11% for nivolumab/chemotherapy and 20% for chemotherapy alone.
Lobectomy was more frequent in the nivolumab/chemotherapy arm (77%) compared to the chemotherapy arm (61%), a difference that Dr. Spicer described as clinically important. He said the difference appears to be attributable to a lower rate of pneumonectomy in the nivolumab/chemotherapy arm (17%) than in the chemotherapy arm (25%).
Despite less extensive lung resection being required, the rate of R0 resection was numerically higher in the nivolumab/chemotherapy arm (83%) than in the chemotherapy arm (78%), said Dr. Spicer.
Length of hospital stay was “within expected ranges” from geographic regions represented in the trial, Dr. Spicer said. Median length of stay was 4.0 and 6.0 days, respectively, for nivolumab/chemotherapy and chemotherapy alone in North America, 9.5 and 13.0 days in Europe, and 11.0 and 13.0 days in Asia.
Likewise, 90-day surgical complications were well within expected ranges, according to the investigator, with anemia, pain, and wound complications being the most commonly reported. Rates were generally similar between study arms, other than a twofold higher rate of pain in the chemotherapy arm, possibly due to the lower rate of minimally invasive surgery or higher rate of conversion to an open procedure, compared to the nivolumab/chemotherapy arm, he said.
Awaiting survival
Rates of 30- and 90-day mortality are expected to be evaluated when survival endpoints are available, according to Dr. Spicer. Beyond pCR rate, event-free survival is also a primary endpoint of the study, while overall survival is a secondary endpoint.
The study was supported by Bristol Myers Squibb. Dr. Spicer reported disclosures related to AstraZeneca, Bristol Myers Squibb Foundation, Merck, and Roche. Dr. Rusch reported research funding with Genelux and Genentech, and travel expenses from Intuitive Surgical.
The addition of nivolumab to neoadjuvant chemotherapy did not impede the feasibility or timing of surgery in patients with resectable lung cancer, according to results from the phase 3 CheckMate 816 trial.
Adding nivolumab to chemotherapy was tolerable and did not increase the rate of surgical complications, investigator Jonathan Spicer, FRCPC, MD, PhD, of McGill University, Montreal, said in his presentation at the annual meeting of the American Society of Clinical Oncology.
His presentation comes about 2 months after the reporting of primary endpoint results of CheckMate 816 (NCT02998528). CheckMate 816 demonstrated that adding nivolumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) in patients with resectable non–small cell lung cancer (NSCLC), according to results presented earlier at the American Association for Cancer Research annual meeting.
“The safety and surgical outcome data reported thus far from CheckMate 816, along with significant improvement in pathological complete response, support nivolumab in combination with chemotherapy as an attractive neoadjuvant option for patients with resectable NSCLC,” said Dr. Spicer (Abstract 8503).
Building on previous experience
The CheckMate 816 study builds on extensive experience in advanced NSCLC that has consistently shown better outcomes, including overall survival, with combinations of chemotherapy and immuno-oncology (IO) agents, compared to chemotherapy alone, said discussant Valerie W. Rusch, MD, of Memorial Sloan Kettering Cancer Center in New York.
Dr. Rusch called out “salient and interesting results” regarding surgical management in CheckMate 816, including a lower rate of surgery cancellations and shorter surgical duration in the chemotherapy-plus-IO arm, compared to the chemotherapy-alone arm.
Furthermore, fewer patients required a pneumonectomy and more patients had a complete resection in the chemotherapy-plus-IO arm, compared to chemotherapy alone, she noted.
“These excellent surgical results, along with the data previously presented at AACR regarding the primary endpoint, help to establish a new standard of neoadjuvant care,” Dr. Rusch said in her presentation.
Study details
CheckMate 816 included 358 patients with newly diagnosed, resectable, stage IB-IIIA NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no known EGFR mutations or ALK alterations. Patients were randomized to receive nivolumab and platinum-doublet chemotherapy (nivolumab/chemotherapy) or chemotherapy alone every 3 weeks, with surgery to be performed within 6 weeks of the last dose of neoadjuvant treatment.
The median age of patients was 64 years in the nivolumab/chemotherapy arm and 65 years in the chemotherapy-alone arm. About one-third of patients had ECOG performance status of one, and about half had squamous tumor histology, Dr. Spicer said in his report. Almost two-thirds of patients had stage IIIA disease.
In the study results previously presented at the AACR meeting, both pCR and major pathologic response were significantly better following neoadjuvant chemotherapy and IO treatment, compared to chemotherapy alone.
In the intention-to-treat analysis, 24.0% of patients treated with nivolumab/chemotherapy achieved a pCR, compared to 2.2% in the chemotherapy arm, amounting to an approximate 12-fold increase in pCR, Dr. Spicer said. Similarly, the rate of major pathologic response in the intention-to-treat analysis was 36.9% and 8.9% for the nivolumab/chemotherapy and chemotherapy arms, respectively.
Surgical results
In his ASCO presentation, Dr. Spicer reported that definitive surgery was canceled in 16% of patients in the nivolumab/chemotherapy arm, and 21% of the chemotherapy arm. Reasons for surgery cancellation generally included patients declining surgery, unresectable disease, and poor lung function. “Cancellation of surgery due to neoadjuvant therapy toxicity was rare,” Dr. Spicer said in his presentation.
Among patients who did proceed to surgery, the median duration of the procedure was 184 minutes in the nivolumab/chemotherapy arm and 217 minutes in the chemotherapy arm. That half-hour difference in favor of the combination arm suggests that the complexity of surgery was not increased by the addition of nivolumab, Dr. Spicer said.
Median time to surgery was about 5 weeks in both arms, which was “well within accepted standards for a neoadjuvant therapeutic approach,” Dr. Spicer said. Most delays beyond 6 weeks were due to administrative issues, and occurred in similar proportions (21% of the nivolumab/chemotherapy arm and 18% of the chemotherapy arm).
The addition of nivolumab to chemotherapy improved pCR rates regardless of baseline stage of disease, according to Dr. Spicer. Furthermore, the depth of pathological regression in the primary tumor was “dramatically different” across stage groupings, he said. Median residual viable tumor percentage in stage IB/II patients was 28% for nivolumab/chemotherapy and 79% for chemotherapy, and in stage IIIA patients, it was 8% for nivolumab/chemotherapy and 70% for chemotherapy.
Overall, thoracotomy was the most frequent surgical approach in this international phase 3 trial, Dr. Spicer said. However, among patients with stage IIIA disease, minimally invasive approaches were used 30% of the time in the nivolumab/chemotherapy arm and 19% in the chemotherapy arm. Conversely, the rate of conversion from a minimally invasive to open approach in patients with stage IIIA disease was 11% for nivolumab/chemotherapy and 20% for chemotherapy alone.
Lobectomy was more frequent in the nivolumab/chemotherapy arm (77%) compared to the chemotherapy arm (61%), a difference that Dr. Spicer described as clinically important. He said the difference appears to be attributable to a lower rate of pneumonectomy in the nivolumab/chemotherapy arm (17%) than in the chemotherapy arm (25%).
Despite less extensive lung resection being required, the rate of R0 resection was numerically higher in the nivolumab/chemotherapy arm (83%) than in the chemotherapy arm (78%), said Dr. Spicer.
Length of hospital stay was “within expected ranges” from geographic regions represented in the trial, Dr. Spicer said. Median length of stay was 4.0 and 6.0 days, respectively, for nivolumab/chemotherapy and chemotherapy alone in North America, 9.5 and 13.0 days in Europe, and 11.0 and 13.0 days in Asia.
Likewise, 90-day surgical complications were well within expected ranges, according to the investigator, with anemia, pain, and wound complications being the most commonly reported. Rates were generally similar between study arms, other than a twofold higher rate of pain in the chemotherapy arm, possibly due to the lower rate of minimally invasive surgery or higher rate of conversion to an open procedure, compared to the nivolumab/chemotherapy arm, he said.
Awaiting survival
Rates of 30- and 90-day mortality are expected to be evaluated when survival endpoints are available, according to Dr. Spicer. Beyond pCR rate, event-free survival is also a primary endpoint of the study, while overall survival is a secondary endpoint.
The study was supported by Bristol Myers Squibb. Dr. Spicer reported disclosures related to AstraZeneca, Bristol Myers Squibb Foundation, Merck, and Roche. Dr. Rusch reported research funding with Genelux and Genentech, and travel expenses from Intuitive Surgical.
The addition of nivolumab to neoadjuvant chemotherapy did not impede the feasibility or timing of surgery in patients with resectable lung cancer, according to results from the phase 3 CheckMate 816 trial.
Adding nivolumab to chemotherapy was tolerable and did not increase the rate of surgical complications, investigator Jonathan Spicer, FRCPC, MD, PhD, of McGill University, Montreal, said in his presentation at the annual meeting of the American Society of Clinical Oncology.
His presentation comes about 2 months after the reporting of primary endpoint results of CheckMate 816 (NCT02998528). CheckMate 816 demonstrated that adding nivolumab to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) in patients with resectable non–small cell lung cancer (NSCLC), according to results presented earlier at the American Association for Cancer Research annual meeting.
“The safety and surgical outcome data reported thus far from CheckMate 816, along with significant improvement in pathological complete response, support nivolumab in combination with chemotherapy as an attractive neoadjuvant option for patients with resectable NSCLC,” said Dr. Spicer (Abstract 8503).
Building on previous experience
The CheckMate 816 study builds on extensive experience in advanced NSCLC that has consistently shown better outcomes, including overall survival, with combinations of chemotherapy and immuno-oncology (IO) agents, compared to chemotherapy alone, said discussant Valerie W. Rusch, MD, of Memorial Sloan Kettering Cancer Center in New York.
Dr. Rusch called out “salient and interesting results” regarding surgical management in CheckMate 816, including a lower rate of surgery cancellations and shorter surgical duration in the chemotherapy-plus-IO arm, compared to the chemotherapy-alone arm.
Furthermore, fewer patients required a pneumonectomy and more patients had a complete resection in the chemotherapy-plus-IO arm, compared to chemotherapy alone, she noted.
“These excellent surgical results, along with the data previously presented at AACR regarding the primary endpoint, help to establish a new standard of neoadjuvant care,” Dr. Rusch said in her presentation.
Study details
CheckMate 816 included 358 patients with newly diagnosed, resectable, stage IB-IIIA NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no known EGFR mutations or ALK alterations. Patients were randomized to receive nivolumab and platinum-doublet chemotherapy (nivolumab/chemotherapy) or chemotherapy alone every 3 weeks, with surgery to be performed within 6 weeks of the last dose of neoadjuvant treatment.
The median age of patients was 64 years in the nivolumab/chemotherapy arm and 65 years in the chemotherapy-alone arm. About one-third of patients had ECOG performance status of one, and about half had squamous tumor histology, Dr. Spicer said in his report. Almost two-thirds of patients had stage IIIA disease.
In the study results previously presented at the AACR meeting, both pCR and major pathologic response were significantly better following neoadjuvant chemotherapy and IO treatment, compared to chemotherapy alone.
In the intention-to-treat analysis, 24.0% of patients treated with nivolumab/chemotherapy achieved a pCR, compared to 2.2% in the chemotherapy arm, amounting to an approximate 12-fold increase in pCR, Dr. Spicer said. Similarly, the rate of major pathologic response in the intention-to-treat analysis was 36.9% and 8.9% for the nivolumab/chemotherapy and chemotherapy arms, respectively.
Surgical results
In his ASCO presentation, Dr. Spicer reported that definitive surgery was canceled in 16% of patients in the nivolumab/chemotherapy arm, and 21% of the chemotherapy arm. Reasons for surgery cancellation generally included patients declining surgery, unresectable disease, and poor lung function. “Cancellation of surgery due to neoadjuvant therapy toxicity was rare,” Dr. Spicer said in his presentation.
Among patients who did proceed to surgery, the median duration of the procedure was 184 minutes in the nivolumab/chemotherapy arm and 217 minutes in the chemotherapy arm. That half-hour difference in favor of the combination arm suggests that the complexity of surgery was not increased by the addition of nivolumab, Dr. Spicer said.
Median time to surgery was about 5 weeks in both arms, which was “well within accepted standards for a neoadjuvant therapeutic approach,” Dr. Spicer said. Most delays beyond 6 weeks were due to administrative issues, and occurred in similar proportions (21% of the nivolumab/chemotherapy arm and 18% of the chemotherapy arm).
The addition of nivolumab to chemotherapy improved pCR rates regardless of baseline stage of disease, according to Dr. Spicer. Furthermore, the depth of pathological regression in the primary tumor was “dramatically different” across stage groupings, he said. Median residual viable tumor percentage in stage IB/II patients was 28% for nivolumab/chemotherapy and 79% for chemotherapy, and in stage IIIA patients, it was 8% for nivolumab/chemotherapy and 70% for chemotherapy.
Overall, thoracotomy was the most frequent surgical approach in this international phase 3 trial, Dr. Spicer said. However, among patients with stage IIIA disease, minimally invasive approaches were used 30% of the time in the nivolumab/chemotherapy arm and 19% in the chemotherapy arm. Conversely, the rate of conversion from a minimally invasive to open approach in patients with stage IIIA disease was 11% for nivolumab/chemotherapy and 20% for chemotherapy alone.
Lobectomy was more frequent in the nivolumab/chemotherapy arm (77%) compared to the chemotherapy arm (61%), a difference that Dr. Spicer described as clinically important. He said the difference appears to be attributable to a lower rate of pneumonectomy in the nivolumab/chemotherapy arm (17%) than in the chemotherapy arm (25%).
Despite less extensive lung resection being required, the rate of R0 resection was numerically higher in the nivolumab/chemotherapy arm (83%) than in the chemotherapy arm (78%), said Dr. Spicer.
Length of hospital stay was “within expected ranges” from geographic regions represented in the trial, Dr. Spicer said. Median length of stay was 4.0 and 6.0 days, respectively, for nivolumab/chemotherapy and chemotherapy alone in North America, 9.5 and 13.0 days in Europe, and 11.0 and 13.0 days in Asia.
Likewise, 90-day surgical complications were well within expected ranges, according to the investigator, with anemia, pain, and wound complications being the most commonly reported. Rates were generally similar between study arms, other than a twofold higher rate of pain in the chemotherapy arm, possibly due to the lower rate of minimally invasive surgery or higher rate of conversion to an open procedure, compared to the nivolumab/chemotherapy arm, he said.
Awaiting survival
Rates of 30- and 90-day mortality are expected to be evaluated when survival endpoints are available, according to Dr. Spicer. Beyond pCR rate, event-free survival is also a primary endpoint of the study, while overall survival is a secondary endpoint.
The study was supported by Bristol Myers Squibb. Dr. Spicer reported disclosures related to AstraZeneca, Bristol Myers Squibb Foundation, Merck, and Roche. Dr. Rusch reported research funding with Genelux and Genentech, and travel expenses from Intuitive Surgical.
FROM ASCO 2021