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Survey Finds Mental Health Issues Increased After Cosmetic Procedure Complications
BALTIMORE — of patients with dermatology-related complications.
The study used an anonymous 40-question survey circulated to a Facebook cosmetic complication support group. Seventy-one of 100 individuals completed the questionnaire, reporting significantly higher rates of mental health issues after their complications than before. Results were presented at the annual conference of the American Society for Laser Medicine and Surgery (ASLMS). Almost all the survey respondents (99%) were female, with 61% aged 25-44 years and 34% aged 45-64 years.
“Cosmetic procedures have increased over the past decade, with procedures being increasingly performed by an evolving variety of providers,” the study’s lead author, Taryn Murray, MD, a dermatologist at Cleveland Clinic, Cleveland, Ohio, told this news organization. “Appropriate patient assessment and counseling and proper procedure technique are important for obtaining safe and effective results. Complications may not only impact patients physically but can also be harmful to their mental health.”
Rise in Mental Health Issues
The study found that before respondents had the treatment that led to their complications, 16% reported a history of generalized anxiety disorder, 15% a history of depression, and 1% a history of either BDD or PTSD. Following the complication, 50% reported a positive depression screening, 63% a positive BDD Questionnaire – Dermatology Version, and 63% a positive Primary Care PTSD screen, Dr. Murray said. “Almost half of respondents (46%) reported thinking about their complication for more than 3 hours a day,” she said in presenting the results.
Dr. Murray said the idea for the study grew out of her experience as a fellow working with Paul Friedman, MD, at the Dermatology and Laser Surgery Center at University of Texas Health in Houston.
“We were seeing a lot of complications,” Dr. Murray said in an interview. “Some of these were local. Some of these patients were flying in from out-of-state looking for help with the complication, and we could see what a mental and emotional burden this put on these patients. They were routinely in the office in tears saying it was interfering with their daily life, it was interfering with their job, saying they were going to lose their job, all because they were so distressed over what was happening to them.”
Yet, the research into psychological distress in patients with dermatologic complications is minimal, Dr. Murray added. “We think that body dysmorphic disorder is prevalent for patients seeking dermatology or plastic surgery services, but I don’t think either of the specialties do a great job in screening people for that when they come for treatment, so I think a lot of it goes undiagnosed. There’s been a trend looking at more at complications lately, but there’s been a gap in the literature.”
The treatments the patients in the survey had were microneedling with radiofrequency (29%), laser (24%), ultrasound for skin tightening (11%), radiofrequency for skin tightening (11%), microneedling (4%), chemical peel (3%), body contouring/sculpting (1%), and “other” (17%).
The study found that the largest share of procedures, 47%, were done by an esthetician/laser technician, followed by a nondermatologist physician (17%), a board-certified dermatologist (14%), an advanced practice provider (12%), and “other” (10%).
Self-reported complications included scarring (38%), hyperpigmentation (26%), erythema (24%), burn (23%), blisters (11%), and hypopigmentation (3%); 71% characterized their complications as “other,” and one respondent reported multiple complications.
“Respondents said they were satisfied with the previous cosmetic care they received,” Dr. Murray said during her presentation at the meeting. “And there was a consensus among the respondents that they did not feel adequately counseled on the risks of the procedure and that it did not meet their expectations and anticipated outcome.”
Take-Home Lesson
The lesson here is that practitioners who perform cosmetic procedures should be well-versed in the task and potential complications, Dr. Murray said in the interview. “If you’re going to be doing a procedure, make sure you know the proper techniques, the proper endpoints, and how to treat if you’re to have a complication,” she said. “If you don’t know how to treat a complication from the device, then you should think twice about using it.”
She also suggested screening patients for potentially undiagnosed mental health disorders. “It can play a role in the initial consultation and potentially any after-care they might need if there is a complication,” she said. “We may not have the adequate tools at this time to know how to best handle these patients and these scenarios, but hopefully my abstract will shed a little more light on it.”
She said she hopes her findings lead to more research in the future.
Asked to comment on the study, Jennifer Lin, MD, assistant professor of dermatology at Brigham and Women’s Hospital and Dana Farber Cancer Institute in Boston, Massachusetts, said one finding of the study stood out to her. “ I was very surprised from her dataset that patients think about it more than 3 hours a day,” she told this news organization. “That’s really significant. We talk about the side effects, but we don’t necessarily talk about the burden of how long the recovery will be or the psychological burden of potentially dealing with it.”
She noted that “there’s a bit of movement” toward developing guidelines for laser treatments, which would address the risk of complications. “That’s the goal: To have better guidelines to avoid these complications in the first place,” Dr. Lin said.
The study findings also point to a need for “premonitoring” individuals before procedures, she added. “We talked about patient selection and make sure someone doesn’t have body dysmorphic disorder, but we don’t formally screen for it,” she said. “We don’t our train our residents to screen for it. And I think doing more pre- and post-testing of how people are affected by laser treatment is going to become more important.”
Dr. Murray disclosed relationships with R2 Technologies. Dr. Lin had no relationships to disclose.
A version of this article appeared on Medscape.com.
BALTIMORE — of patients with dermatology-related complications.
The study used an anonymous 40-question survey circulated to a Facebook cosmetic complication support group. Seventy-one of 100 individuals completed the questionnaire, reporting significantly higher rates of mental health issues after their complications than before. Results were presented at the annual conference of the American Society for Laser Medicine and Surgery (ASLMS). Almost all the survey respondents (99%) were female, with 61% aged 25-44 years and 34% aged 45-64 years.
“Cosmetic procedures have increased over the past decade, with procedures being increasingly performed by an evolving variety of providers,” the study’s lead author, Taryn Murray, MD, a dermatologist at Cleveland Clinic, Cleveland, Ohio, told this news organization. “Appropriate patient assessment and counseling and proper procedure technique are important for obtaining safe and effective results. Complications may not only impact patients physically but can also be harmful to their mental health.”
Rise in Mental Health Issues
The study found that before respondents had the treatment that led to their complications, 16% reported a history of generalized anxiety disorder, 15% a history of depression, and 1% a history of either BDD or PTSD. Following the complication, 50% reported a positive depression screening, 63% a positive BDD Questionnaire – Dermatology Version, and 63% a positive Primary Care PTSD screen, Dr. Murray said. “Almost half of respondents (46%) reported thinking about their complication for more than 3 hours a day,” she said in presenting the results.
Dr. Murray said the idea for the study grew out of her experience as a fellow working with Paul Friedman, MD, at the Dermatology and Laser Surgery Center at University of Texas Health in Houston.
“We were seeing a lot of complications,” Dr. Murray said in an interview. “Some of these were local. Some of these patients were flying in from out-of-state looking for help with the complication, and we could see what a mental and emotional burden this put on these patients. They were routinely in the office in tears saying it was interfering with their daily life, it was interfering with their job, saying they were going to lose their job, all because they were so distressed over what was happening to them.”
Yet, the research into psychological distress in patients with dermatologic complications is minimal, Dr. Murray added. “We think that body dysmorphic disorder is prevalent for patients seeking dermatology or plastic surgery services, but I don’t think either of the specialties do a great job in screening people for that when they come for treatment, so I think a lot of it goes undiagnosed. There’s been a trend looking at more at complications lately, but there’s been a gap in the literature.”
The treatments the patients in the survey had were microneedling with radiofrequency (29%), laser (24%), ultrasound for skin tightening (11%), radiofrequency for skin tightening (11%), microneedling (4%), chemical peel (3%), body contouring/sculpting (1%), and “other” (17%).
The study found that the largest share of procedures, 47%, were done by an esthetician/laser technician, followed by a nondermatologist physician (17%), a board-certified dermatologist (14%), an advanced practice provider (12%), and “other” (10%).
Self-reported complications included scarring (38%), hyperpigmentation (26%), erythema (24%), burn (23%), blisters (11%), and hypopigmentation (3%); 71% characterized their complications as “other,” and one respondent reported multiple complications.
“Respondents said they were satisfied with the previous cosmetic care they received,” Dr. Murray said during her presentation at the meeting. “And there was a consensus among the respondents that they did not feel adequately counseled on the risks of the procedure and that it did not meet their expectations and anticipated outcome.”
Take-Home Lesson
The lesson here is that practitioners who perform cosmetic procedures should be well-versed in the task and potential complications, Dr. Murray said in the interview. “If you’re going to be doing a procedure, make sure you know the proper techniques, the proper endpoints, and how to treat if you’re to have a complication,” she said. “If you don’t know how to treat a complication from the device, then you should think twice about using it.”
She also suggested screening patients for potentially undiagnosed mental health disorders. “It can play a role in the initial consultation and potentially any after-care they might need if there is a complication,” she said. “We may not have the adequate tools at this time to know how to best handle these patients and these scenarios, but hopefully my abstract will shed a little more light on it.”
She said she hopes her findings lead to more research in the future.
Asked to comment on the study, Jennifer Lin, MD, assistant professor of dermatology at Brigham and Women’s Hospital and Dana Farber Cancer Institute in Boston, Massachusetts, said one finding of the study stood out to her. “ I was very surprised from her dataset that patients think about it more than 3 hours a day,” she told this news organization. “That’s really significant. We talk about the side effects, but we don’t necessarily talk about the burden of how long the recovery will be or the psychological burden of potentially dealing with it.”
She noted that “there’s a bit of movement” toward developing guidelines for laser treatments, which would address the risk of complications. “That’s the goal: To have better guidelines to avoid these complications in the first place,” Dr. Lin said.
The study findings also point to a need for “premonitoring” individuals before procedures, she added. “We talked about patient selection and make sure someone doesn’t have body dysmorphic disorder, but we don’t formally screen for it,” she said. “We don’t our train our residents to screen for it. And I think doing more pre- and post-testing of how people are affected by laser treatment is going to become more important.”
Dr. Murray disclosed relationships with R2 Technologies. Dr. Lin had no relationships to disclose.
A version of this article appeared on Medscape.com.
BALTIMORE — of patients with dermatology-related complications.
The study used an anonymous 40-question survey circulated to a Facebook cosmetic complication support group. Seventy-one of 100 individuals completed the questionnaire, reporting significantly higher rates of mental health issues after their complications than before. Results were presented at the annual conference of the American Society for Laser Medicine and Surgery (ASLMS). Almost all the survey respondents (99%) were female, with 61% aged 25-44 years and 34% aged 45-64 years.
“Cosmetic procedures have increased over the past decade, with procedures being increasingly performed by an evolving variety of providers,” the study’s lead author, Taryn Murray, MD, a dermatologist at Cleveland Clinic, Cleveland, Ohio, told this news organization. “Appropriate patient assessment and counseling and proper procedure technique are important for obtaining safe and effective results. Complications may not only impact patients physically but can also be harmful to their mental health.”
Rise in Mental Health Issues
The study found that before respondents had the treatment that led to their complications, 16% reported a history of generalized anxiety disorder, 15% a history of depression, and 1% a history of either BDD or PTSD. Following the complication, 50% reported a positive depression screening, 63% a positive BDD Questionnaire – Dermatology Version, and 63% a positive Primary Care PTSD screen, Dr. Murray said. “Almost half of respondents (46%) reported thinking about their complication for more than 3 hours a day,” she said in presenting the results.
Dr. Murray said the idea for the study grew out of her experience as a fellow working with Paul Friedman, MD, at the Dermatology and Laser Surgery Center at University of Texas Health in Houston.
“We were seeing a lot of complications,” Dr. Murray said in an interview. “Some of these were local. Some of these patients were flying in from out-of-state looking for help with the complication, and we could see what a mental and emotional burden this put on these patients. They were routinely in the office in tears saying it was interfering with their daily life, it was interfering with their job, saying they were going to lose their job, all because they were so distressed over what was happening to them.”
Yet, the research into psychological distress in patients with dermatologic complications is minimal, Dr. Murray added. “We think that body dysmorphic disorder is prevalent for patients seeking dermatology or plastic surgery services, but I don’t think either of the specialties do a great job in screening people for that when they come for treatment, so I think a lot of it goes undiagnosed. There’s been a trend looking at more at complications lately, but there’s been a gap in the literature.”
The treatments the patients in the survey had were microneedling with radiofrequency (29%), laser (24%), ultrasound for skin tightening (11%), radiofrequency for skin tightening (11%), microneedling (4%), chemical peel (3%), body contouring/sculpting (1%), and “other” (17%).
The study found that the largest share of procedures, 47%, were done by an esthetician/laser technician, followed by a nondermatologist physician (17%), a board-certified dermatologist (14%), an advanced practice provider (12%), and “other” (10%).
Self-reported complications included scarring (38%), hyperpigmentation (26%), erythema (24%), burn (23%), blisters (11%), and hypopigmentation (3%); 71% characterized their complications as “other,” and one respondent reported multiple complications.
“Respondents said they were satisfied with the previous cosmetic care they received,” Dr. Murray said during her presentation at the meeting. “And there was a consensus among the respondents that they did not feel adequately counseled on the risks of the procedure and that it did not meet their expectations and anticipated outcome.”
Take-Home Lesson
The lesson here is that practitioners who perform cosmetic procedures should be well-versed in the task and potential complications, Dr. Murray said in the interview. “If you’re going to be doing a procedure, make sure you know the proper techniques, the proper endpoints, and how to treat if you’re to have a complication,” she said. “If you don’t know how to treat a complication from the device, then you should think twice about using it.”
She also suggested screening patients for potentially undiagnosed mental health disorders. “It can play a role in the initial consultation and potentially any after-care they might need if there is a complication,” she said. “We may not have the adequate tools at this time to know how to best handle these patients and these scenarios, but hopefully my abstract will shed a little more light on it.”
She said she hopes her findings lead to more research in the future.
Asked to comment on the study, Jennifer Lin, MD, assistant professor of dermatology at Brigham and Women’s Hospital and Dana Farber Cancer Institute in Boston, Massachusetts, said one finding of the study stood out to her. “ I was very surprised from her dataset that patients think about it more than 3 hours a day,” she told this news organization. “That’s really significant. We talk about the side effects, but we don’t necessarily talk about the burden of how long the recovery will be or the psychological burden of potentially dealing with it.”
She noted that “there’s a bit of movement” toward developing guidelines for laser treatments, which would address the risk of complications. “That’s the goal: To have better guidelines to avoid these complications in the first place,” Dr. Lin said.
The study findings also point to a need for “premonitoring” individuals before procedures, she added. “We talked about patient selection and make sure someone doesn’t have body dysmorphic disorder, but we don’t formally screen for it,” she said. “We don’t our train our residents to screen for it. And I think doing more pre- and post-testing of how people are affected by laser treatment is going to become more important.”
Dr. Murray disclosed relationships with R2 Technologies. Dr. Lin had no relationships to disclose.
A version of this article appeared on Medscape.com.
FROM ASLMS 2024
One-Minute Speech Test Could Help Assess Dementia Risk
BUDAPEST, HUNGARY — , suggests research.
János Kálmán, MD, PhD, and colleagues at the University of Szeged in Hungary have developed an automated speech analysis approach called the Speech-Gap Test (S-GAP Test) that is unique because it focuses on the temporal changes made when someone talks. This means it does not overcomplicate matters by also assessing the phonetics and semantics of speech, Dr. Kálmán said.
Dr. Kálmán presented his findings at the 32nd European Congress of Psychiatry.
Temporal Speech Parameters
The test analyzes parameters such as how quickly someone speaks, whether they hesitate when they talk, how long the hesitation lasts, and how many silent pauses they make. This can be done with a mere 60-second sample of speech, Dr. Kálmán said, noting that other automated speech and language tools currently in development need much longer audio samples.
“We tried different approaches and we finally ended up with the temporal speech parameters because these are not culture-dependent, not education-dependent, and could be more reliable than the semantic parts of [speech] analysis,” he explained.
The analysis of temporal speech parameters is also not language-dependent. Although the S-GAP Test was developed using audio samples from native Hungarian speakers, Dr. Kálmán and his collaborators have shown that it works just as well with samples from native English and German speakers. They now plan to validate the test further using samples from native Spanish speakers.
For Screening, Not Diagnosis
Currently, “the only purpose of this tool would be initial screening,” Dr. Kálmán said at the congress. It is not for diagnosis, and there is no intention to get it registered as a medical device.
A national survey of primary care physicians conducted by Dr. Kálmán and collaborators showed that there was little time for performing standard cognitive tests during the average consultation. Thus, the original idea was that the S-GAP Test would be an aid to help primary care physicians quickly flag whether a patient might have cognitive problems that needed further assessment at a memory clinic or by more specialist neurology services.
The goalposts have since been moved, from developing a pure telemedicine solution to a more widespread application that perhaps anyone could buy and download from the internet or using a smartphone.
Dr. Kálmán doesn’t discount developing a more sophisticated version of the S-GAP Test in the future that combines temporal speech parameters with biomarkers for mild cognitive impairment or Alzheimer’s disease and could be used in memory clinics and by neurologists for the purpose of diagnosis.
Detect to Prevent?
The big question is: What happens to all the people that could be flagged as needing further assessment using tools such as the S-GAP Test?
Tackling risk factors for dementia will probably be key, said Robert Perneckzy, MD, MBA, professor of translational dementia research at Ludwig Maximilian University of Munich, Imperial College London, and the University of Sheffield.
According to the Lancet Commission on dementia, there are 12 potentially modifiable risk factors for dementia. Their influence varies throughout the life course, but certain early events, such as the level of education attained, can’t be modified in an older patient.
That said, there are many risk factors that might still be influenced later in life, such as adequately treating comorbid conditions such as diabetes, and addressing alcohol consumption and smoking practices.
“We can do things in terms of personal risk, risk mitigation, which have a huge effect on dementia risk much later in life,” said Dr. Perneckzy.
“The speech-based assessments are another opportunity to save our time as doctors to do assessments before someone comes to the memory clinic,” he said.
The S-GAP Test is under development by the University of Szeged. Dr. Kálmán is a co-inventor. Dr. Perneckzy had no relevant conflicts of interest but has helped validate the S-GAP Test in the German language.
A version of this article appeared on Medscape.com.
BUDAPEST, HUNGARY — , suggests research.
János Kálmán, MD, PhD, and colleagues at the University of Szeged in Hungary have developed an automated speech analysis approach called the Speech-Gap Test (S-GAP Test) that is unique because it focuses on the temporal changes made when someone talks. This means it does not overcomplicate matters by also assessing the phonetics and semantics of speech, Dr. Kálmán said.
Dr. Kálmán presented his findings at the 32nd European Congress of Psychiatry.
Temporal Speech Parameters
The test analyzes parameters such as how quickly someone speaks, whether they hesitate when they talk, how long the hesitation lasts, and how many silent pauses they make. This can be done with a mere 60-second sample of speech, Dr. Kálmán said, noting that other automated speech and language tools currently in development need much longer audio samples.
“We tried different approaches and we finally ended up with the temporal speech parameters because these are not culture-dependent, not education-dependent, and could be more reliable than the semantic parts of [speech] analysis,” he explained.
The analysis of temporal speech parameters is also not language-dependent. Although the S-GAP Test was developed using audio samples from native Hungarian speakers, Dr. Kálmán and his collaborators have shown that it works just as well with samples from native English and German speakers. They now plan to validate the test further using samples from native Spanish speakers.
For Screening, Not Diagnosis
Currently, “the only purpose of this tool would be initial screening,” Dr. Kálmán said at the congress. It is not for diagnosis, and there is no intention to get it registered as a medical device.
A national survey of primary care physicians conducted by Dr. Kálmán and collaborators showed that there was little time for performing standard cognitive tests during the average consultation. Thus, the original idea was that the S-GAP Test would be an aid to help primary care physicians quickly flag whether a patient might have cognitive problems that needed further assessment at a memory clinic or by more specialist neurology services.
The goalposts have since been moved, from developing a pure telemedicine solution to a more widespread application that perhaps anyone could buy and download from the internet or using a smartphone.
Dr. Kálmán doesn’t discount developing a more sophisticated version of the S-GAP Test in the future that combines temporal speech parameters with biomarkers for mild cognitive impairment or Alzheimer’s disease and could be used in memory clinics and by neurologists for the purpose of diagnosis.
Detect to Prevent?
The big question is: What happens to all the people that could be flagged as needing further assessment using tools such as the S-GAP Test?
Tackling risk factors for dementia will probably be key, said Robert Perneckzy, MD, MBA, professor of translational dementia research at Ludwig Maximilian University of Munich, Imperial College London, and the University of Sheffield.
According to the Lancet Commission on dementia, there are 12 potentially modifiable risk factors for dementia. Their influence varies throughout the life course, but certain early events, such as the level of education attained, can’t be modified in an older patient.
That said, there are many risk factors that might still be influenced later in life, such as adequately treating comorbid conditions such as diabetes, and addressing alcohol consumption and smoking practices.
“We can do things in terms of personal risk, risk mitigation, which have a huge effect on dementia risk much later in life,” said Dr. Perneckzy.
“The speech-based assessments are another opportunity to save our time as doctors to do assessments before someone comes to the memory clinic,” he said.
The S-GAP Test is under development by the University of Szeged. Dr. Kálmán is a co-inventor. Dr. Perneckzy had no relevant conflicts of interest but has helped validate the S-GAP Test in the German language.
A version of this article appeared on Medscape.com.
BUDAPEST, HUNGARY — , suggests research.
János Kálmán, MD, PhD, and colleagues at the University of Szeged in Hungary have developed an automated speech analysis approach called the Speech-Gap Test (S-GAP Test) that is unique because it focuses on the temporal changes made when someone talks. This means it does not overcomplicate matters by also assessing the phonetics and semantics of speech, Dr. Kálmán said.
Dr. Kálmán presented his findings at the 32nd European Congress of Psychiatry.
Temporal Speech Parameters
The test analyzes parameters such as how quickly someone speaks, whether they hesitate when they talk, how long the hesitation lasts, and how many silent pauses they make. This can be done with a mere 60-second sample of speech, Dr. Kálmán said, noting that other automated speech and language tools currently in development need much longer audio samples.
“We tried different approaches and we finally ended up with the temporal speech parameters because these are not culture-dependent, not education-dependent, and could be more reliable than the semantic parts of [speech] analysis,” he explained.
The analysis of temporal speech parameters is also not language-dependent. Although the S-GAP Test was developed using audio samples from native Hungarian speakers, Dr. Kálmán and his collaborators have shown that it works just as well with samples from native English and German speakers. They now plan to validate the test further using samples from native Spanish speakers.
For Screening, Not Diagnosis
Currently, “the only purpose of this tool would be initial screening,” Dr. Kálmán said at the congress. It is not for diagnosis, and there is no intention to get it registered as a medical device.
A national survey of primary care physicians conducted by Dr. Kálmán and collaborators showed that there was little time for performing standard cognitive tests during the average consultation. Thus, the original idea was that the S-GAP Test would be an aid to help primary care physicians quickly flag whether a patient might have cognitive problems that needed further assessment at a memory clinic or by more specialist neurology services.
The goalposts have since been moved, from developing a pure telemedicine solution to a more widespread application that perhaps anyone could buy and download from the internet or using a smartphone.
Dr. Kálmán doesn’t discount developing a more sophisticated version of the S-GAP Test in the future that combines temporal speech parameters with biomarkers for mild cognitive impairment or Alzheimer’s disease and could be used in memory clinics and by neurologists for the purpose of diagnosis.
Detect to Prevent?
The big question is: What happens to all the people that could be flagged as needing further assessment using tools such as the S-GAP Test?
Tackling risk factors for dementia will probably be key, said Robert Perneckzy, MD, MBA, professor of translational dementia research at Ludwig Maximilian University of Munich, Imperial College London, and the University of Sheffield.
According to the Lancet Commission on dementia, there are 12 potentially modifiable risk factors for dementia. Their influence varies throughout the life course, but certain early events, such as the level of education attained, can’t be modified in an older patient.
That said, there are many risk factors that might still be influenced later in life, such as adequately treating comorbid conditions such as diabetes, and addressing alcohol consumption and smoking practices.
“We can do things in terms of personal risk, risk mitigation, which have a huge effect on dementia risk much later in life,” said Dr. Perneckzy.
“The speech-based assessments are another opportunity to save our time as doctors to do assessments before someone comes to the memory clinic,” he said.
The S-GAP Test is under development by the University of Szeged. Dr. Kálmán is a co-inventor. Dr. Perneckzy had no relevant conflicts of interest but has helped validate the S-GAP Test in the German language.
A version of this article appeared on Medscape.com.
FROM THE EUROPEAN CONGRESS OF PSYCHIATRY
Blood Test Shows Promise for Improving CRC Screening
say the authors of new research.
Rachel B. Issaka, MD, MAS, of the Fred Hutchinson Cancer Center, Seattle, presented the clinical data, which was published in The New England Journal of Medicine, at the American Association for Cancer Research annual meeting.
The authors of the study evaluated the performance of a cfDNA blood-based test in a population eligible for colorectal cancer screening. The researchers found that the test had high sensitivity for the detection of colorectal cancer and high specificity for advanced precancerous lesions.
This novel blood test could improve screening adherence and, ultimately, reduce colorectal cancer-related mortality, Dr. Issaka said during her presentation.
“This test has the potential to help us reach the 80% screening target in colorectal cancer. However, this will depend on many factors, including access, implementation, follow-up colonoscopy, and characteristics of the test,” Dr. Issaka said in an interview.
She added that, when approved for broader use, anyone who wants to use this blood test for colorectal cancer screening should have a frank conversation with their healthcare provider.
“Considering the person’s age, medical history, family history, and any potential symptoms, and how the test performs will dictate if it’s the right test for that person versus another screening strategy,” Dr. Issaka explained.
The Blood Test Detects Colorectal Cancer With High Accuracy
The investigators of the observational ECLIPSE trial evaluated the performance of the cfDNA-based blood test in 7861 individuals who were eligible for colorectal cancer screening. The study population included people from more than 200 rural and urban sites across 34 states, including community hospitals, private practices, gastroenterology clinics, and academic centers. “The study enrolled a diverse cohort that is reflective of the demographics of the intended use population in the US,” Dr. Issaka said during her talk.
The co-primary outcomes of the study were the test’s sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia.
In her presentation, Dr. Issaka highlighted that the test had 83.1% (95% confidence interval [CI], 72.2%-90.3%) sensitivity for the detection of colorectal cancer, meaning that it was able to correctly identify most participants with the disease. The test’s sensitivity was even higher (87.5%; 95% CI, 75.3%-94.1%) for stage I, II, or III colorectal cancer. “These are the stages at which early intervention can have the greatest impact on patient prognosis,” Dr. Issaka said.
Moreover, the blood test showed 89.6% (95% CI, 88.8%-90.3%) specificity for advanced neoplasia, including colorectal cancer and advanced precancerous lesions. The specificity of the test for negative colonoscopy results (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0%-90.7%).
Dr. Issaka highlighted that this cfDNA assay is the first blood-based test with performance comparable to current guideline-recommended noninvasive options for CRC.
The Blood Test Shows Limited Ability To Detect Advanced Precancerous Lesions
During her presentation, Dr. Issaka acknowledged that the cfDNA-based blood test had a lower sensitivity (13.2%; 95% CI, 11.3%-15.3%) for the detection of advanced precancerous lesions, suggesting that it may be more effective at identifying established cancers than early-stage precancerous changes. Low sensitivity was also observed for high-grade dysplasia (22.6%; 95% CI, 11.4%-39.8%). However, she emphasized that the test could still play a valuable role in a comprehensive screening approach, potentially serving as a first-line tool to identify individuals who would then undergo follow-up colonoscopy.
“Although blood-based tests perform well at finding cancers, they do not do so well at finding precancerous polyps. This is relevant because colorectal cancer is one of the few cancers that we can prevent by finding and removing precancerous polyps,” Folasade P. May, MD, PhD, MPhil, said in an interview.
“Users must also understand that if the test result is abnormal, a colonoscopy is required to look for cancers and polyps that might have caused the abnormal result,” added Dr. May, associate professor at UCLA. She was not involved in the study.
Clinical Implications and Future Steps
According to the study published in the NEJM, colorectal cancer is the third most commonly diagnosed cancer in the United States, and early detection is crucial for effective treatment. However, over a third of eligible individuals are not up to date with recommended screening.
During her talk, Dr. Issaka noted that colonoscopy is the most commonly used screening method for colorectal cancer. What contributes to the low adherence to getting a colonoscopy among the eligible population is that some find it inconvenient, and the test is invasive, she added.
According to Dr. May, the key advantage of cfDNA-based screening is that many people will find it easier to complete a blood test than the currently available screening tests.
“This option may allow us to screen individuals that we have previously struggled to convince to get screened for colorectal cancer,” she said.
In an interview, Dr. Issaka acknowledged that the potential public health impact of any noninvasive screening test depends on how many people with abnormal results complete a follow-up colonoscopy. “This is an important quality metric to track,” she said.
In an interview, Dr. Issaka emphasized that comparing this cfDNA blood test with emerging blood tests and other noninvasive screening strategies will empower patients and clinicians to select the right test at the right time for the right patient.
She added that the study was conducted in an average-risk screening population and that further research is needed to evaluate the test’s performance in higher-risk groups and to assess its real-world impact on screening adherence and colorectal cancer-related outcomes.
Commenting on potential challenges with implementing this cfDNA blood test in clinical practice, Dr. May said, “As we consider incorporating blood-based tests into clinical practice, some challenges include cost, equitable access to tests and follow-up, performance in young adults who are newly eligible for screening, and follow-up after abnormal results.”
She added that, if there is uptake of these tests, it will be important to track how that impacts colorectal cancer screening rates, stage at diagnosis, and whether there is stage migration, incidence, and mortality.
“At this time, I feel that these tests are appropriate for individuals who will not or cannot participate in one of the currently recommended screening tests. These include colonoscopy and stool-based tests, like FIT and FIT-DNA,” Dr. May concluded.
Dr. Issaka reported financial relationships with the National Institutes of Health/National Cancer Institute, American College of Gastroenterology, and Guardant Health Inc. Dr. May reported financial relationships with Takeda, Medtronic, Johnson & Johnson, Saint Supply, Exact Sciences, Freenome, Geneoscopy, Guardant Health, InterVenn, Natura, National Institutes of Health/National Cancer Institute, Veterans Affairs HSR&D, Broad Institute, Stand up to Cancer, and NRG Oncology.
say the authors of new research.
Rachel B. Issaka, MD, MAS, of the Fred Hutchinson Cancer Center, Seattle, presented the clinical data, which was published in The New England Journal of Medicine, at the American Association for Cancer Research annual meeting.
The authors of the study evaluated the performance of a cfDNA blood-based test in a population eligible for colorectal cancer screening. The researchers found that the test had high sensitivity for the detection of colorectal cancer and high specificity for advanced precancerous lesions.
This novel blood test could improve screening adherence and, ultimately, reduce colorectal cancer-related mortality, Dr. Issaka said during her presentation.
“This test has the potential to help us reach the 80% screening target in colorectal cancer. However, this will depend on many factors, including access, implementation, follow-up colonoscopy, and characteristics of the test,” Dr. Issaka said in an interview.
She added that, when approved for broader use, anyone who wants to use this blood test for colorectal cancer screening should have a frank conversation with their healthcare provider.
“Considering the person’s age, medical history, family history, and any potential symptoms, and how the test performs will dictate if it’s the right test for that person versus another screening strategy,” Dr. Issaka explained.
The Blood Test Detects Colorectal Cancer With High Accuracy
The investigators of the observational ECLIPSE trial evaluated the performance of the cfDNA-based blood test in 7861 individuals who were eligible for colorectal cancer screening. The study population included people from more than 200 rural and urban sites across 34 states, including community hospitals, private practices, gastroenterology clinics, and academic centers. “The study enrolled a diverse cohort that is reflective of the demographics of the intended use population in the US,” Dr. Issaka said during her talk.
The co-primary outcomes of the study were the test’s sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia.
In her presentation, Dr. Issaka highlighted that the test had 83.1% (95% confidence interval [CI], 72.2%-90.3%) sensitivity for the detection of colorectal cancer, meaning that it was able to correctly identify most participants with the disease. The test’s sensitivity was even higher (87.5%; 95% CI, 75.3%-94.1%) for stage I, II, or III colorectal cancer. “These are the stages at which early intervention can have the greatest impact on patient prognosis,” Dr. Issaka said.
Moreover, the blood test showed 89.6% (95% CI, 88.8%-90.3%) specificity for advanced neoplasia, including colorectal cancer and advanced precancerous lesions. The specificity of the test for negative colonoscopy results (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0%-90.7%).
Dr. Issaka highlighted that this cfDNA assay is the first blood-based test with performance comparable to current guideline-recommended noninvasive options for CRC.
The Blood Test Shows Limited Ability To Detect Advanced Precancerous Lesions
During her presentation, Dr. Issaka acknowledged that the cfDNA-based blood test had a lower sensitivity (13.2%; 95% CI, 11.3%-15.3%) for the detection of advanced precancerous lesions, suggesting that it may be more effective at identifying established cancers than early-stage precancerous changes. Low sensitivity was also observed for high-grade dysplasia (22.6%; 95% CI, 11.4%-39.8%). However, she emphasized that the test could still play a valuable role in a comprehensive screening approach, potentially serving as a first-line tool to identify individuals who would then undergo follow-up colonoscopy.
“Although blood-based tests perform well at finding cancers, they do not do so well at finding precancerous polyps. This is relevant because colorectal cancer is one of the few cancers that we can prevent by finding and removing precancerous polyps,” Folasade P. May, MD, PhD, MPhil, said in an interview.
“Users must also understand that if the test result is abnormal, a colonoscopy is required to look for cancers and polyps that might have caused the abnormal result,” added Dr. May, associate professor at UCLA. She was not involved in the study.
Clinical Implications and Future Steps
According to the study published in the NEJM, colorectal cancer is the third most commonly diagnosed cancer in the United States, and early detection is crucial for effective treatment. However, over a third of eligible individuals are not up to date with recommended screening.
During her talk, Dr. Issaka noted that colonoscopy is the most commonly used screening method for colorectal cancer. What contributes to the low adherence to getting a colonoscopy among the eligible population is that some find it inconvenient, and the test is invasive, she added.
According to Dr. May, the key advantage of cfDNA-based screening is that many people will find it easier to complete a blood test than the currently available screening tests.
“This option may allow us to screen individuals that we have previously struggled to convince to get screened for colorectal cancer,” she said.
In an interview, Dr. Issaka acknowledged that the potential public health impact of any noninvasive screening test depends on how many people with abnormal results complete a follow-up colonoscopy. “This is an important quality metric to track,” she said.
In an interview, Dr. Issaka emphasized that comparing this cfDNA blood test with emerging blood tests and other noninvasive screening strategies will empower patients and clinicians to select the right test at the right time for the right patient.
She added that the study was conducted in an average-risk screening population and that further research is needed to evaluate the test’s performance in higher-risk groups and to assess its real-world impact on screening adherence and colorectal cancer-related outcomes.
Commenting on potential challenges with implementing this cfDNA blood test in clinical practice, Dr. May said, “As we consider incorporating blood-based tests into clinical practice, some challenges include cost, equitable access to tests and follow-up, performance in young adults who are newly eligible for screening, and follow-up after abnormal results.”
She added that, if there is uptake of these tests, it will be important to track how that impacts colorectal cancer screening rates, stage at diagnosis, and whether there is stage migration, incidence, and mortality.
“At this time, I feel that these tests are appropriate for individuals who will not or cannot participate in one of the currently recommended screening tests. These include colonoscopy and stool-based tests, like FIT and FIT-DNA,” Dr. May concluded.
Dr. Issaka reported financial relationships with the National Institutes of Health/National Cancer Institute, American College of Gastroenterology, and Guardant Health Inc. Dr. May reported financial relationships with Takeda, Medtronic, Johnson & Johnson, Saint Supply, Exact Sciences, Freenome, Geneoscopy, Guardant Health, InterVenn, Natura, National Institutes of Health/National Cancer Institute, Veterans Affairs HSR&D, Broad Institute, Stand up to Cancer, and NRG Oncology.
say the authors of new research.
Rachel B. Issaka, MD, MAS, of the Fred Hutchinson Cancer Center, Seattle, presented the clinical data, which was published in The New England Journal of Medicine, at the American Association for Cancer Research annual meeting.
The authors of the study evaluated the performance of a cfDNA blood-based test in a population eligible for colorectal cancer screening. The researchers found that the test had high sensitivity for the detection of colorectal cancer and high specificity for advanced precancerous lesions.
This novel blood test could improve screening adherence and, ultimately, reduce colorectal cancer-related mortality, Dr. Issaka said during her presentation.
“This test has the potential to help us reach the 80% screening target in colorectal cancer. However, this will depend on many factors, including access, implementation, follow-up colonoscopy, and characteristics of the test,” Dr. Issaka said in an interview.
She added that, when approved for broader use, anyone who wants to use this blood test for colorectal cancer screening should have a frank conversation with their healthcare provider.
“Considering the person’s age, medical history, family history, and any potential symptoms, and how the test performs will dictate if it’s the right test for that person versus another screening strategy,” Dr. Issaka explained.
The Blood Test Detects Colorectal Cancer With High Accuracy
The investigators of the observational ECLIPSE trial evaluated the performance of the cfDNA-based blood test in 7861 individuals who were eligible for colorectal cancer screening. The study population included people from more than 200 rural and urban sites across 34 states, including community hospitals, private practices, gastroenterology clinics, and academic centers. “The study enrolled a diverse cohort that is reflective of the demographics of the intended use population in the US,” Dr. Issaka said during her talk.
The co-primary outcomes of the study were the test’s sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia.
In her presentation, Dr. Issaka highlighted that the test had 83.1% (95% confidence interval [CI], 72.2%-90.3%) sensitivity for the detection of colorectal cancer, meaning that it was able to correctly identify most participants with the disease. The test’s sensitivity was even higher (87.5%; 95% CI, 75.3%-94.1%) for stage I, II, or III colorectal cancer. “These are the stages at which early intervention can have the greatest impact on patient prognosis,” Dr. Issaka said.
Moreover, the blood test showed 89.6% (95% CI, 88.8%-90.3%) specificity for advanced neoplasia, including colorectal cancer and advanced precancerous lesions. The specificity of the test for negative colonoscopy results (no colorectal cancer, advanced precancerous lesions, or nonadvanced precancerous lesions) was 89.9% (95% CI, 89.0%-90.7%).
Dr. Issaka highlighted that this cfDNA assay is the first blood-based test with performance comparable to current guideline-recommended noninvasive options for CRC.
The Blood Test Shows Limited Ability To Detect Advanced Precancerous Lesions
During her presentation, Dr. Issaka acknowledged that the cfDNA-based blood test had a lower sensitivity (13.2%; 95% CI, 11.3%-15.3%) for the detection of advanced precancerous lesions, suggesting that it may be more effective at identifying established cancers than early-stage precancerous changes. Low sensitivity was also observed for high-grade dysplasia (22.6%; 95% CI, 11.4%-39.8%). However, she emphasized that the test could still play a valuable role in a comprehensive screening approach, potentially serving as a first-line tool to identify individuals who would then undergo follow-up colonoscopy.
“Although blood-based tests perform well at finding cancers, they do not do so well at finding precancerous polyps. This is relevant because colorectal cancer is one of the few cancers that we can prevent by finding and removing precancerous polyps,” Folasade P. May, MD, PhD, MPhil, said in an interview.
“Users must also understand that if the test result is abnormal, a colonoscopy is required to look for cancers and polyps that might have caused the abnormal result,” added Dr. May, associate professor at UCLA. She was not involved in the study.
Clinical Implications and Future Steps
According to the study published in the NEJM, colorectal cancer is the third most commonly diagnosed cancer in the United States, and early detection is crucial for effective treatment. However, over a third of eligible individuals are not up to date with recommended screening.
During her talk, Dr. Issaka noted that colonoscopy is the most commonly used screening method for colorectal cancer. What contributes to the low adherence to getting a colonoscopy among the eligible population is that some find it inconvenient, and the test is invasive, she added.
According to Dr. May, the key advantage of cfDNA-based screening is that many people will find it easier to complete a blood test than the currently available screening tests.
“This option may allow us to screen individuals that we have previously struggled to convince to get screened for colorectal cancer,” she said.
In an interview, Dr. Issaka acknowledged that the potential public health impact of any noninvasive screening test depends on how many people with abnormal results complete a follow-up colonoscopy. “This is an important quality metric to track,” she said.
In an interview, Dr. Issaka emphasized that comparing this cfDNA blood test with emerging blood tests and other noninvasive screening strategies will empower patients and clinicians to select the right test at the right time for the right patient.
She added that the study was conducted in an average-risk screening population and that further research is needed to evaluate the test’s performance in higher-risk groups and to assess its real-world impact on screening adherence and colorectal cancer-related outcomes.
Commenting on potential challenges with implementing this cfDNA blood test in clinical practice, Dr. May said, “As we consider incorporating blood-based tests into clinical practice, some challenges include cost, equitable access to tests and follow-up, performance in young adults who are newly eligible for screening, and follow-up after abnormal results.”
She added that, if there is uptake of these tests, it will be important to track how that impacts colorectal cancer screening rates, stage at diagnosis, and whether there is stage migration, incidence, and mortality.
“At this time, I feel that these tests are appropriate for individuals who will not or cannot participate in one of the currently recommended screening tests. These include colonoscopy and stool-based tests, like FIT and FIT-DNA,” Dr. May concluded.
Dr. Issaka reported financial relationships with the National Institutes of Health/National Cancer Institute, American College of Gastroenterology, and Guardant Health Inc. Dr. May reported financial relationships with Takeda, Medtronic, Johnson & Johnson, Saint Supply, Exact Sciences, Freenome, Geneoscopy, Guardant Health, InterVenn, Natura, National Institutes of Health/National Cancer Institute, Veterans Affairs HSR&D, Broad Institute, Stand up to Cancer, and NRG Oncology.
Positive Results for Intranasal Oxytocin in Adults With Autism
BUDAPEST, HUNGARY — Twice daily intranasal oxytocin has been associated with improved social functioning, quality of life, and overall symptoms in adults with autism spectrum disorder (ASD), results of a small randomized control trial showed.
“One of the challenges for adults with autism is experiencing poor social interactions and difficulties in making friends. Insufficient social support from peers, friends, and family members can contribute to loneliness in adolescents with ASD, which in turn leads to anxiety, sadness, and social isolation,” said study investigator Saba Faraji Niri, MD, assistant professor of psychiatry, Tehran University of Medical Sciences in Iran.
Recent US data show it is relatively common. In addition, previous research suggests intranasal oxytocin significantly increases activity in brain regions that play a role in establishing social interactions.
To evaluate the therapeutic effects and safety of intranasal oxytocin the researchers randomly assigned 39 adult patients with ASD to receive intranasal oxytocin or placebo with 24 units administered every 12 hours for 8 weeks.
Dr. Faraji Niri said study participants were required to stop all psychotropic medications for at least 8 weeks prior to study entry.
Participants were assessed at baseline and weeks 4 and 8 using the Autism Quotient, Ritvo Autism Asperger Diagnostic Scale — Revised (RAADS-R), Social Responsiveness Scale (SRS), Clinical Global Impression (CGI) scale, and the World Health Organization Quality of Life-BREF (WHOQL-BREF) questionnaire. Adverse events were also evaluated.
Dr. Faraji Niri said that those receiving intranasal oxytocin showed clinical improvement on RAADS-R scores (P = .010), as well as on the social communication subscale of the SRS (P = .002), the CGI scale (P = .000), and the physical (P = .004), psychological (P = .006), and social relationships (P = .046) domains of the WHOQL-BREF.
However, although the findings were positive, she said at this point it’s not possible to draw any definitive conclusions. She noted the study had several potential confounders. These included differences in baseline levels of endogenous oxytocin among study participants individuals, as well as difference in required treatment doses, which were adjusted by age and sex. The presence of comorbidities and interactions with other treatments could also affect the results.
Commenting on the findings for this news organization, session chair Szabolcs Kéri, PhD, Professor, Sztárai Institute, University of Tokaj, Sárospatak, Hungary, said the use of oxytocin for ASD is controversial. He said that, while the research contributes to the scientific debate, the clinical significance of the findings is unclear.
The investigators and Dr Keri reported no relevant financial disclosures.
A version of this article appeared on Medscape.com .
BUDAPEST, HUNGARY — Twice daily intranasal oxytocin has been associated with improved social functioning, quality of life, and overall symptoms in adults with autism spectrum disorder (ASD), results of a small randomized control trial showed.
“One of the challenges for adults with autism is experiencing poor social interactions and difficulties in making friends. Insufficient social support from peers, friends, and family members can contribute to loneliness in adolescents with ASD, which in turn leads to anxiety, sadness, and social isolation,” said study investigator Saba Faraji Niri, MD, assistant professor of psychiatry, Tehran University of Medical Sciences in Iran.
Recent US data show it is relatively common. In addition, previous research suggests intranasal oxytocin significantly increases activity in brain regions that play a role in establishing social interactions.
To evaluate the therapeutic effects and safety of intranasal oxytocin the researchers randomly assigned 39 adult patients with ASD to receive intranasal oxytocin or placebo with 24 units administered every 12 hours for 8 weeks.
Dr. Faraji Niri said study participants were required to stop all psychotropic medications for at least 8 weeks prior to study entry.
Participants were assessed at baseline and weeks 4 and 8 using the Autism Quotient, Ritvo Autism Asperger Diagnostic Scale — Revised (RAADS-R), Social Responsiveness Scale (SRS), Clinical Global Impression (CGI) scale, and the World Health Organization Quality of Life-BREF (WHOQL-BREF) questionnaire. Adverse events were also evaluated.
Dr. Faraji Niri said that those receiving intranasal oxytocin showed clinical improvement on RAADS-R scores (P = .010), as well as on the social communication subscale of the SRS (P = .002), the CGI scale (P = .000), and the physical (P = .004), psychological (P = .006), and social relationships (P = .046) domains of the WHOQL-BREF.
However, although the findings were positive, she said at this point it’s not possible to draw any definitive conclusions. She noted the study had several potential confounders. These included differences in baseline levels of endogenous oxytocin among study participants individuals, as well as difference in required treatment doses, which were adjusted by age and sex. The presence of comorbidities and interactions with other treatments could also affect the results.
Commenting on the findings for this news organization, session chair Szabolcs Kéri, PhD, Professor, Sztárai Institute, University of Tokaj, Sárospatak, Hungary, said the use of oxytocin for ASD is controversial. He said that, while the research contributes to the scientific debate, the clinical significance of the findings is unclear.
The investigators and Dr Keri reported no relevant financial disclosures.
A version of this article appeared on Medscape.com .
BUDAPEST, HUNGARY — Twice daily intranasal oxytocin has been associated with improved social functioning, quality of life, and overall symptoms in adults with autism spectrum disorder (ASD), results of a small randomized control trial showed.
“One of the challenges for adults with autism is experiencing poor social interactions and difficulties in making friends. Insufficient social support from peers, friends, and family members can contribute to loneliness in adolescents with ASD, which in turn leads to anxiety, sadness, and social isolation,” said study investigator Saba Faraji Niri, MD, assistant professor of psychiatry, Tehran University of Medical Sciences in Iran.
Recent US data show it is relatively common. In addition, previous research suggests intranasal oxytocin significantly increases activity in brain regions that play a role in establishing social interactions.
To evaluate the therapeutic effects and safety of intranasal oxytocin the researchers randomly assigned 39 adult patients with ASD to receive intranasal oxytocin or placebo with 24 units administered every 12 hours for 8 weeks.
Dr. Faraji Niri said study participants were required to stop all psychotropic medications for at least 8 weeks prior to study entry.
Participants were assessed at baseline and weeks 4 and 8 using the Autism Quotient, Ritvo Autism Asperger Diagnostic Scale — Revised (RAADS-R), Social Responsiveness Scale (SRS), Clinical Global Impression (CGI) scale, and the World Health Organization Quality of Life-BREF (WHOQL-BREF) questionnaire. Adverse events were also evaluated.
Dr. Faraji Niri said that those receiving intranasal oxytocin showed clinical improvement on RAADS-R scores (P = .010), as well as on the social communication subscale of the SRS (P = .002), the CGI scale (P = .000), and the physical (P = .004), psychological (P = .006), and social relationships (P = .046) domains of the WHOQL-BREF.
However, although the findings were positive, she said at this point it’s not possible to draw any definitive conclusions. She noted the study had several potential confounders. These included differences in baseline levels of endogenous oxytocin among study participants individuals, as well as difference in required treatment doses, which were adjusted by age and sex. The presence of comorbidities and interactions with other treatments could also affect the results.
Commenting on the findings for this news organization, session chair Szabolcs Kéri, PhD, Professor, Sztárai Institute, University of Tokaj, Sárospatak, Hungary, said the use of oxytocin for ASD is controversial. He said that, while the research contributes to the scientific debate, the clinical significance of the findings is unclear.
The investigators and Dr Keri reported no relevant financial disclosures.
A version of this article appeared on Medscape.com .
Prominent Researcher Describes Pivot From ALS Treatment to Prevention
DENVER — After working for decades in a field littered with promising but failed clinical trials, a prominent researcher in amyotrophic lateral sclerosis (ALS) has decided to turn her attention to prevention, a direction of research that she thinks has more promise.
According to the gene-time hypothesis, duration of exposure to noxious chemicals and genetic susceptibility are key drivers of ALS risk, explained Eva Feldman, MD, PhD, director of the ALS Center of Excellence at the University of Michigan, Ann Arbor. She believes that existing research in risk modification is already promising.
“I think ALS prevention is real and attainable,” she said as this year’s recipient of the Sheila Essey Award for significant contributions in ALS research.
In describing her “pivot” to prevention from treatment at the 2024 annual meeting of the American Academy of Neurology, Dr. Feldman described her growing pessimism about treating a disease that has so consistently resisted even stabilization, let alone cure.
“I spent 10 years trying to repurpose IGF-1 as an ALS therapy. We took it from preclinical work all the way to a phase 3 multicenter trial, but in the end no effect was seen,” Dr. Feldman said,
This was followed by another 10 years spent on the promise of stem cells. In this case, she was eventually involved in two multicenter trials. In fact, trials are still ongoing in Europe, but Dr. Feldman said this strategy is “no longer going forward in the United States,” and she no longer anticipates favorable results.
The New Focus on Prevention
The basic concept in the prevention studies she is now working on with Stephen Goutman, MD, a frequent coauthor, and other colleagues at her center, is that the duration of exposure to persistent organic pollutants (POPs), along with some degree of genetic predisposition, determines risk for ALS. The simple idea is the reducing exposure will reduce ALS risk.
There is already substantial support for the underlying time-gene hypothesis, according to Dr. Feldman. Among several examples, she described work with 122 POPS that appear individually and in many cases collectively to correlate with ALS risk. Recent work with an environmental risk score (ERS) that permits studies of risk when accounting for exposure to families of pollutants, has supported these as potentially modifiable risks.
A high ERS “correlates with an ALS risk that is 3 to 4 times higher than a low score,” she said. In addition, those ALS patients with a high relative to a low ERS have a significant 0.6-year reduction in median survival.
Some specific POPs, such as pesticides, correlate with increased risk by themselves, but Dr. Feldman has begun focusing on occupational exposures, particularly in industries that are most likely to increase exposure POPs. Several of the POPs most implicated in ALS, such as polychlorinated biphenyls used in coolants and lubricants, organochlorine pesticides, and polybrominated diphenyl esters, are already banned or mostly banned in the United States, but they persist in the environment and remain legal elsewhere.
Dr. Feldman reported no potential conflicts of interest.
DENVER — After working for decades in a field littered with promising but failed clinical trials, a prominent researcher in amyotrophic lateral sclerosis (ALS) has decided to turn her attention to prevention, a direction of research that she thinks has more promise.
According to the gene-time hypothesis, duration of exposure to noxious chemicals and genetic susceptibility are key drivers of ALS risk, explained Eva Feldman, MD, PhD, director of the ALS Center of Excellence at the University of Michigan, Ann Arbor. She believes that existing research in risk modification is already promising.
“I think ALS prevention is real and attainable,” she said as this year’s recipient of the Sheila Essey Award for significant contributions in ALS research.
In describing her “pivot” to prevention from treatment at the 2024 annual meeting of the American Academy of Neurology, Dr. Feldman described her growing pessimism about treating a disease that has so consistently resisted even stabilization, let alone cure.
“I spent 10 years trying to repurpose IGF-1 as an ALS therapy. We took it from preclinical work all the way to a phase 3 multicenter trial, but in the end no effect was seen,” Dr. Feldman said,
This was followed by another 10 years spent on the promise of stem cells. In this case, she was eventually involved in two multicenter trials. In fact, trials are still ongoing in Europe, but Dr. Feldman said this strategy is “no longer going forward in the United States,” and she no longer anticipates favorable results.
The New Focus on Prevention
The basic concept in the prevention studies she is now working on with Stephen Goutman, MD, a frequent coauthor, and other colleagues at her center, is that the duration of exposure to persistent organic pollutants (POPs), along with some degree of genetic predisposition, determines risk for ALS. The simple idea is the reducing exposure will reduce ALS risk.
There is already substantial support for the underlying time-gene hypothesis, according to Dr. Feldman. Among several examples, she described work with 122 POPS that appear individually and in many cases collectively to correlate with ALS risk. Recent work with an environmental risk score (ERS) that permits studies of risk when accounting for exposure to families of pollutants, has supported these as potentially modifiable risks.
A high ERS “correlates with an ALS risk that is 3 to 4 times higher than a low score,” she said. In addition, those ALS patients with a high relative to a low ERS have a significant 0.6-year reduction in median survival.
Some specific POPs, such as pesticides, correlate with increased risk by themselves, but Dr. Feldman has begun focusing on occupational exposures, particularly in industries that are most likely to increase exposure POPs. Several of the POPs most implicated in ALS, such as polychlorinated biphenyls used in coolants and lubricants, organochlorine pesticides, and polybrominated diphenyl esters, are already banned or mostly banned in the United States, but they persist in the environment and remain legal elsewhere.
Dr. Feldman reported no potential conflicts of interest.
DENVER — After working for decades in a field littered with promising but failed clinical trials, a prominent researcher in amyotrophic lateral sclerosis (ALS) has decided to turn her attention to prevention, a direction of research that she thinks has more promise.
According to the gene-time hypothesis, duration of exposure to noxious chemicals and genetic susceptibility are key drivers of ALS risk, explained Eva Feldman, MD, PhD, director of the ALS Center of Excellence at the University of Michigan, Ann Arbor. She believes that existing research in risk modification is already promising.
“I think ALS prevention is real and attainable,” she said as this year’s recipient of the Sheila Essey Award for significant contributions in ALS research.
In describing her “pivot” to prevention from treatment at the 2024 annual meeting of the American Academy of Neurology, Dr. Feldman described her growing pessimism about treating a disease that has so consistently resisted even stabilization, let alone cure.
“I spent 10 years trying to repurpose IGF-1 as an ALS therapy. We took it from preclinical work all the way to a phase 3 multicenter trial, but in the end no effect was seen,” Dr. Feldman said,
This was followed by another 10 years spent on the promise of stem cells. In this case, she was eventually involved in two multicenter trials. In fact, trials are still ongoing in Europe, but Dr. Feldman said this strategy is “no longer going forward in the United States,” and she no longer anticipates favorable results.
The New Focus on Prevention
The basic concept in the prevention studies she is now working on with Stephen Goutman, MD, a frequent coauthor, and other colleagues at her center, is that the duration of exposure to persistent organic pollutants (POPs), along with some degree of genetic predisposition, determines risk for ALS. The simple idea is the reducing exposure will reduce ALS risk.
There is already substantial support for the underlying time-gene hypothesis, according to Dr. Feldman. Among several examples, she described work with 122 POPS that appear individually and in many cases collectively to correlate with ALS risk. Recent work with an environmental risk score (ERS) that permits studies of risk when accounting for exposure to families of pollutants, has supported these as potentially modifiable risks.
A high ERS “correlates with an ALS risk that is 3 to 4 times higher than a low score,” she said. In addition, those ALS patients with a high relative to a low ERS have a significant 0.6-year reduction in median survival.
Some specific POPs, such as pesticides, correlate with increased risk by themselves, but Dr. Feldman has begun focusing on occupational exposures, particularly in industries that are most likely to increase exposure POPs. Several of the POPs most implicated in ALS, such as polychlorinated biphenyls used in coolants and lubricants, organochlorine pesticides, and polybrominated diphenyl esters, are already banned or mostly banned in the United States, but they persist in the environment and remain legal elsewhere.
Dr. Feldman reported no potential conflicts of interest.
FROM AAN 2024
How New ICI Combos Change Bladder Cancer Management
according to Thomas W. Flaig, MD, vice chancellor for research at the University of Colorado Anschutz Medical Campus, Aurora.
Combination therapies involving enfortumab and nivolumab are demonstrating success in recent studies and have been incorporated into the latest guidelines, Dr. Flaig said in a presentation at the National Comprehensive Cancer Network (NCCN) annual conference.
What's New in The Updated Guidelines?
Advances in the treatment options for metastatic urothelial carcinoma in the last decade have been dramatic, with ongoing developments and new emerging treatment options, Dr. Flaig told the audience of his session.
This has led to the identification of new and effective immune checkpoint inhibitor combinations. Consequently, immune checkpoint inhibitors are currently included in all preferred/other recommended first-line treatment regimens, he said.
“Enfortumab vedotin plus pembrolizumab is now the sole preferred first-line regimen for locally advanced or metastatic disease.” Based on the recent research, the mindset regarding cisplatin-eligible patient selection may be changing, he added.
“We have used cisplatin eligibility as a key factor in determining first-line therapy for years, and that paradigm is now shifting with the emergence of enfortumab plus pembrolizumab, a new non–cisplatin containing regimen” Dr. Flaig noted.
Although the optimal choice for second- or third-line therapy after immune checkpoint inhibitors is not well-defined, options include platinum regimens, antibody-drug conjugate, and erdafitinib in eligible patients, he said.
Other Current Strategies for Localized Bladder Cancer Management
The incidence of bladder cancer has been stable for decades, with minimal therapeutic developments until the approval of immune checkpoint inhibitors in the last decade, Dr. Flaig said.
Bladder cancer is more common in older adults, with an average onset age of 73 years, and most patients (75%) are male, he said. Comorbid disease is common in these patients, and many have a history of smoking, Dr. Flaig added.
The traditional medical approach to treating bladder cancer has been based on combination therapies including cisplatin. This has also reflected the approach used in the treatment of lung cancer, historically, Dr. Flaig said.
Cisplatin, while effective, is a challenging therapy to administer and is not an option for all bladder cancer patients because of potential adverse effects, he noted. Antibody drug conjugates and immune checkpoint inhibitors are new alternatives for some who are not able to receive cisplatin.
What are the New Options for Treating Metastatic Urothelial Bladder Cancer?
The approval of antibody drug conjugates offers new treatment with a “specific target and therapeutic payload,” said Dr. Flaig in his presentation. Two antibody drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been approved by the US Food and Drug Administration (FDA), he said. Enforumab vedotin was approved by the FDA in 2021 for adults with locally advanced or metastatic urothelial cancer for subsequent line therapy in select patients. In a 2021 study published in The New England Journal of Medicine, the primary outcome of overall response rate was significantly greater in patients with advanced urothelial carcinoma who were treated with enfortumab vedotin than in those treated with standard chemotherapy (overall response rate [ORR] 40.6% vs 17.9%, respectively).
Side effects associated with enfortumab vedotin “are intrinsic to the payload toxicity and the target distribution. Ideally, the target would be present on all of the cancer cells and none of the normal tissue,” said Dr. Flaig. With enfortumab, specific toxicities included neuropathy, skin reactions, and blood glucose elevation/diabetic ketoacidosis, he said.
A second agent, sacituzumab govitecan, was approved by the FDA for metastatic urothelial cancer patients in 2021, based on data from the TROPHY-U-O1 phase 2 open-label study of 113 individuals. In that study, the ORR was 27% at a median follow-up of 9.1 months. Adverse events included neutropenia, leukopenia, and diarrhea.
What Do the Latest Studies of Combination Therapy Show?
Immune checkpoint inhibitor combinations are significantly changing the landscape of bladder cancer treatment, Dr. Flaig explained.
A recent phase 3 study published in 2024 in The New England Journal of Medicine comparing enfortumab vedotin plus pembrolizumab to platinum-based combination chemotherapy showed an overall response rate of 67.7% vs 44.4% in favor of enfortumab/pembrolizumab, said Dr. Flaig. In addition, the risk of disease progression or death was approximately 55% lower in the enfortumab vedotin-pembrolizumab group vs the chemotherapy group (hazard ratio [HR], 0.45; P less than .001) and the median progression-free survival was approximately doubled (12.5 months vs 6.3 months).
Dr. Flaig described this study as “very notable”because “the enfortumab plus pembrolizumab arm was clearly more effective than the long-standing chemotherapy arm, now becoming the preferred, first-line treatment in the NCCN guidelines. Based on preliminary results of the study, this combination was approved by the FDA in 2023 for locally advanced or metastatic urothelial cancer patients regardless of their eligibility for cisplatin.
Another promising combination, nivolumab plus gemcitabine-cisplatin, was associated with significantly longer overall and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma, Dr. Flaig said. The therapy was approved by the FDA in March 2024 for first-line therapy.
In a study of 608 patients published in The New England Journal of Medicine, median overall survival was 21.7 months for the nivolumab group vs 18.9 months for the gemcitabine-cisplatin alone group. The overall response rates were 57.6% in the nivolumab group vs 43.1% in the gemcitabine-cisplatin–alone group, and complete response rates were 21.7% and 11.8%, respectively. Serious adverse events (grade 3 or higher) were similar between the groups (61.8% and 51.7%, respectively).
What About Targeted Therapy?
Erdafitinib, a tyrosine kinase inhibitor of FGFR1–4, was approved by the FDA in January 2024 for adults with locally advanced or metastatic urothelial carcinoma who had susceptible FGFR3 genetic alterations, said Dr. Flaig, during his presentation. The limitation of this treatment to only those patients with an FGFR3 mutation is a recent update in its use, he noted.
“Up to 20% of patients with advanced urothelial carcinoma have FGFR alterations,” he said. In an open-label phase 2 study of 99 individuals with unresectable or metastatic urothelial carcinoma, past chemotherapy, and FGFR alterations, confirmed response to erdafitinib was 40% with a median overall survival of 13.8 months.
Dr. Flaig disclosed grant/research support from Agensys; Astellas Pharma US; AstraZeneca Pharmaceuticals LP; Bristol Myers Squibb; Genentech, Inc.; Janssen Pharmaceutica Products, LP; Merck & Co.; Sanofi-Aventis U.S.; and SeaGen. He also disclosed equity interest/stock options and intellectual property rights in Aurora Oncology, and serving as a consultant or scientific advisor for Janssen Pharmaceutica Product, LP, and Criterium, Inc.
according to Thomas W. Flaig, MD, vice chancellor for research at the University of Colorado Anschutz Medical Campus, Aurora.
Combination therapies involving enfortumab and nivolumab are demonstrating success in recent studies and have been incorporated into the latest guidelines, Dr. Flaig said in a presentation at the National Comprehensive Cancer Network (NCCN) annual conference.
What's New in The Updated Guidelines?
Advances in the treatment options for metastatic urothelial carcinoma in the last decade have been dramatic, with ongoing developments and new emerging treatment options, Dr. Flaig told the audience of his session.
This has led to the identification of new and effective immune checkpoint inhibitor combinations. Consequently, immune checkpoint inhibitors are currently included in all preferred/other recommended first-line treatment regimens, he said.
“Enfortumab vedotin plus pembrolizumab is now the sole preferred first-line regimen for locally advanced or metastatic disease.” Based on the recent research, the mindset regarding cisplatin-eligible patient selection may be changing, he added.
“We have used cisplatin eligibility as a key factor in determining first-line therapy for years, and that paradigm is now shifting with the emergence of enfortumab plus pembrolizumab, a new non–cisplatin containing regimen” Dr. Flaig noted.
Although the optimal choice for second- or third-line therapy after immune checkpoint inhibitors is not well-defined, options include platinum regimens, antibody-drug conjugate, and erdafitinib in eligible patients, he said.
Other Current Strategies for Localized Bladder Cancer Management
The incidence of bladder cancer has been stable for decades, with minimal therapeutic developments until the approval of immune checkpoint inhibitors in the last decade, Dr. Flaig said.
Bladder cancer is more common in older adults, with an average onset age of 73 years, and most patients (75%) are male, he said. Comorbid disease is common in these patients, and many have a history of smoking, Dr. Flaig added.
The traditional medical approach to treating bladder cancer has been based on combination therapies including cisplatin. This has also reflected the approach used in the treatment of lung cancer, historically, Dr. Flaig said.
Cisplatin, while effective, is a challenging therapy to administer and is not an option for all bladder cancer patients because of potential adverse effects, he noted. Antibody drug conjugates and immune checkpoint inhibitors are new alternatives for some who are not able to receive cisplatin.
What are the New Options for Treating Metastatic Urothelial Bladder Cancer?
The approval of antibody drug conjugates offers new treatment with a “specific target and therapeutic payload,” said Dr. Flaig in his presentation. Two antibody drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been approved by the US Food and Drug Administration (FDA), he said. Enforumab vedotin was approved by the FDA in 2021 for adults with locally advanced or metastatic urothelial cancer for subsequent line therapy in select patients. In a 2021 study published in The New England Journal of Medicine, the primary outcome of overall response rate was significantly greater in patients with advanced urothelial carcinoma who were treated with enfortumab vedotin than in those treated with standard chemotherapy (overall response rate [ORR] 40.6% vs 17.9%, respectively).
Side effects associated with enfortumab vedotin “are intrinsic to the payload toxicity and the target distribution. Ideally, the target would be present on all of the cancer cells and none of the normal tissue,” said Dr. Flaig. With enfortumab, specific toxicities included neuropathy, skin reactions, and blood glucose elevation/diabetic ketoacidosis, he said.
A second agent, sacituzumab govitecan, was approved by the FDA for metastatic urothelial cancer patients in 2021, based on data from the TROPHY-U-O1 phase 2 open-label study of 113 individuals. In that study, the ORR was 27% at a median follow-up of 9.1 months. Adverse events included neutropenia, leukopenia, and diarrhea.
What Do the Latest Studies of Combination Therapy Show?
Immune checkpoint inhibitor combinations are significantly changing the landscape of bladder cancer treatment, Dr. Flaig explained.
A recent phase 3 study published in 2024 in The New England Journal of Medicine comparing enfortumab vedotin plus pembrolizumab to platinum-based combination chemotherapy showed an overall response rate of 67.7% vs 44.4% in favor of enfortumab/pembrolizumab, said Dr. Flaig. In addition, the risk of disease progression or death was approximately 55% lower in the enfortumab vedotin-pembrolizumab group vs the chemotherapy group (hazard ratio [HR], 0.45; P less than .001) and the median progression-free survival was approximately doubled (12.5 months vs 6.3 months).
Dr. Flaig described this study as “very notable”because “the enfortumab plus pembrolizumab arm was clearly more effective than the long-standing chemotherapy arm, now becoming the preferred, first-line treatment in the NCCN guidelines. Based on preliminary results of the study, this combination was approved by the FDA in 2023 for locally advanced or metastatic urothelial cancer patients regardless of their eligibility for cisplatin.
Another promising combination, nivolumab plus gemcitabine-cisplatin, was associated with significantly longer overall and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma, Dr. Flaig said. The therapy was approved by the FDA in March 2024 for first-line therapy.
In a study of 608 patients published in The New England Journal of Medicine, median overall survival was 21.7 months for the nivolumab group vs 18.9 months for the gemcitabine-cisplatin alone group. The overall response rates were 57.6% in the nivolumab group vs 43.1% in the gemcitabine-cisplatin–alone group, and complete response rates were 21.7% and 11.8%, respectively. Serious adverse events (grade 3 or higher) were similar between the groups (61.8% and 51.7%, respectively).
What About Targeted Therapy?
Erdafitinib, a tyrosine kinase inhibitor of FGFR1–4, was approved by the FDA in January 2024 for adults with locally advanced or metastatic urothelial carcinoma who had susceptible FGFR3 genetic alterations, said Dr. Flaig, during his presentation. The limitation of this treatment to only those patients with an FGFR3 mutation is a recent update in its use, he noted.
“Up to 20% of patients with advanced urothelial carcinoma have FGFR alterations,” he said. In an open-label phase 2 study of 99 individuals with unresectable or metastatic urothelial carcinoma, past chemotherapy, and FGFR alterations, confirmed response to erdafitinib was 40% with a median overall survival of 13.8 months.
Dr. Flaig disclosed grant/research support from Agensys; Astellas Pharma US; AstraZeneca Pharmaceuticals LP; Bristol Myers Squibb; Genentech, Inc.; Janssen Pharmaceutica Products, LP; Merck & Co.; Sanofi-Aventis U.S.; and SeaGen. He also disclosed equity interest/stock options and intellectual property rights in Aurora Oncology, and serving as a consultant or scientific advisor for Janssen Pharmaceutica Product, LP, and Criterium, Inc.
according to Thomas W. Flaig, MD, vice chancellor for research at the University of Colorado Anschutz Medical Campus, Aurora.
Combination therapies involving enfortumab and nivolumab are demonstrating success in recent studies and have been incorporated into the latest guidelines, Dr. Flaig said in a presentation at the National Comprehensive Cancer Network (NCCN) annual conference.
What's New in The Updated Guidelines?
Advances in the treatment options for metastatic urothelial carcinoma in the last decade have been dramatic, with ongoing developments and new emerging treatment options, Dr. Flaig told the audience of his session.
This has led to the identification of new and effective immune checkpoint inhibitor combinations. Consequently, immune checkpoint inhibitors are currently included in all preferred/other recommended first-line treatment regimens, he said.
“Enfortumab vedotin plus pembrolizumab is now the sole preferred first-line regimen for locally advanced or metastatic disease.” Based on the recent research, the mindset regarding cisplatin-eligible patient selection may be changing, he added.
“We have used cisplatin eligibility as a key factor in determining first-line therapy for years, and that paradigm is now shifting with the emergence of enfortumab plus pembrolizumab, a new non–cisplatin containing regimen” Dr. Flaig noted.
Although the optimal choice for second- or third-line therapy after immune checkpoint inhibitors is not well-defined, options include platinum regimens, antibody-drug conjugate, and erdafitinib in eligible patients, he said.
Other Current Strategies for Localized Bladder Cancer Management
The incidence of bladder cancer has been stable for decades, with minimal therapeutic developments until the approval of immune checkpoint inhibitors in the last decade, Dr. Flaig said.
Bladder cancer is more common in older adults, with an average onset age of 73 years, and most patients (75%) are male, he said. Comorbid disease is common in these patients, and many have a history of smoking, Dr. Flaig added.
The traditional medical approach to treating bladder cancer has been based on combination therapies including cisplatin. This has also reflected the approach used in the treatment of lung cancer, historically, Dr. Flaig said.
Cisplatin, while effective, is a challenging therapy to administer and is not an option for all bladder cancer patients because of potential adverse effects, he noted. Antibody drug conjugates and immune checkpoint inhibitors are new alternatives for some who are not able to receive cisplatin.
What are the New Options for Treating Metastatic Urothelial Bladder Cancer?
The approval of antibody drug conjugates offers new treatment with a “specific target and therapeutic payload,” said Dr. Flaig in his presentation. Two antibody drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been approved by the US Food and Drug Administration (FDA), he said. Enforumab vedotin was approved by the FDA in 2021 for adults with locally advanced or metastatic urothelial cancer for subsequent line therapy in select patients. In a 2021 study published in The New England Journal of Medicine, the primary outcome of overall response rate was significantly greater in patients with advanced urothelial carcinoma who were treated with enfortumab vedotin than in those treated with standard chemotherapy (overall response rate [ORR] 40.6% vs 17.9%, respectively).
Side effects associated with enfortumab vedotin “are intrinsic to the payload toxicity and the target distribution. Ideally, the target would be present on all of the cancer cells and none of the normal tissue,” said Dr. Flaig. With enfortumab, specific toxicities included neuropathy, skin reactions, and blood glucose elevation/diabetic ketoacidosis, he said.
A second agent, sacituzumab govitecan, was approved by the FDA for metastatic urothelial cancer patients in 2021, based on data from the TROPHY-U-O1 phase 2 open-label study of 113 individuals. In that study, the ORR was 27% at a median follow-up of 9.1 months. Adverse events included neutropenia, leukopenia, and diarrhea.
What Do the Latest Studies of Combination Therapy Show?
Immune checkpoint inhibitor combinations are significantly changing the landscape of bladder cancer treatment, Dr. Flaig explained.
A recent phase 3 study published in 2024 in The New England Journal of Medicine comparing enfortumab vedotin plus pembrolizumab to platinum-based combination chemotherapy showed an overall response rate of 67.7% vs 44.4% in favor of enfortumab/pembrolizumab, said Dr. Flaig. In addition, the risk of disease progression or death was approximately 55% lower in the enfortumab vedotin-pembrolizumab group vs the chemotherapy group (hazard ratio [HR], 0.45; P less than .001) and the median progression-free survival was approximately doubled (12.5 months vs 6.3 months).
Dr. Flaig described this study as “very notable”because “the enfortumab plus pembrolizumab arm was clearly more effective than the long-standing chemotherapy arm, now becoming the preferred, first-line treatment in the NCCN guidelines. Based on preliminary results of the study, this combination was approved by the FDA in 2023 for locally advanced or metastatic urothelial cancer patients regardless of their eligibility for cisplatin.
Another promising combination, nivolumab plus gemcitabine-cisplatin, was associated with significantly longer overall and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma, Dr. Flaig said. The therapy was approved by the FDA in March 2024 for first-line therapy.
In a study of 608 patients published in The New England Journal of Medicine, median overall survival was 21.7 months for the nivolumab group vs 18.9 months for the gemcitabine-cisplatin alone group. The overall response rates were 57.6% in the nivolumab group vs 43.1% in the gemcitabine-cisplatin–alone group, and complete response rates were 21.7% and 11.8%, respectively. Serious adverse events (grade 3 or higher) were similar between the groups (61.8% and 51.7%, respectively).
What About Targeted Therapy?
Erdafitinib, a tyrosine kinase inhibitor of FGFR1–4, was approved by the FDA in January 2024 for adults with locally advanced or metastatic urothelial carcinoma who had susceptible FGFR3 genetic alterations, said Dr. Flaig, during his presentation. The limitation of this treatment to only those patients with an FGFR3 mutation is a recent update in its use, he noted.
“Up to 20% of patients with advanced urothelial carcinoma have FGFR alterations,” he said. In an open-label phase 2 study of 99 individuals with unresectable or metastatic urothelial carcinoma, past chemotherapy, and FGFR alterations, confirmed response to erdafitinib was 40% with a median overall survival of 13.8 months.
Dr. Flaig disclosed grant/research support from Agensys; Astellas Pharma US; AstraZeneca Pharmaceuticals LP; Bristol Myers Squibb; Genentech, Inc.; Janssen Pharmaceutica Products, LP; Merck & Co.; Sanofi-Aventis U.S.; and SeaGen. He also disclosed equity interest/stock options and intellectual property rights in Aurora Oncology, and serving as a consultant or scientific advisor for Janssen Pharmaceutica Product, LP, and Criterium, Inc.
FROM NCCN 2024
Antidiabetic Drugs That Lower Stroke Risk Do So By Unclear Mechanisms
DENVER —
In patients with type 2 diabetes mellitus (T2DM), the evidence is strong that “they are not working through glycemic control per se,” according to Larry B. Goldstein, MD, chair of neurology, University of Kentucky School of Medicine, Louisville. “But it is not yet clear what the mechanism of benefit is.”
In the past, several large randomized studies, such as the ACCORD trial, provided compelling evidence that tighter glycemic control does not translate into meaningful protection across stroke. Performed before many of the modern therapies were available, this lack of protection was observed with essentially “no heterogeneity across specific drugs,” according to Dr. Goldstein.
In long-term results from ACCORD, published in 2011, the odds ratio for a fatal or nonfatal stroke was a nonsignificant 0.97 in favor of tight glycemic control relative to standard control. The wide confidence intervals ruled out any hint of statistical significance (95% CI, 0.77-1.33; P = .85). Dr. Goldstein provided data from numerous other studies and meta-analyses that drew the same conclusion.
Stroke Prevention With Antidiabetic Drugs
“What has changed is that we have new ways of glycemic control, and some of these do show protection against stroke,” Dr. Goldstein said. Yet, the newer drugs do not do a better job at sustained reductions of HbA1c or other measures of reaching lower blood glucose reductions when adherence is similar.
“The level of glucose control with the newer agents is really about the same,” Dr. Goldstein said at the annual meeting of the American Academy of Neurology, where he led a symposium called Controversies in Stroke Treatment and Prevention.
The newer agents, such as sodium glucose co-transport-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have been associated with significant and clinically meaningful reductions in cardiovascular events. However, it is not clear that even these two medications perform similarly for stroke prevention specifically.
Of these two drug classes, Dr. Goldstein said the evidence most strongly supports GLP-1 receptor agonists. He cited one meta-analysis of eight randomized studies that calculated a risk reduction of about 15% whether calculated for fatal or nonfatal strokes. For each the protection was highly statistically significant (P = .0002 and P < .001, respectively).
In contrast, the effect of SGLT-2 inhibitors is weaker. In a study that distilled data from large cardiovascular trials with GLP-1RA, SGLT2i, dipeptidyl peptidase-4 inhibitors (DPP4i), and pioglitazone, a thiazolidinedione, only GLP-1RA drugs were associated with a highly significant (P < .001) reduction in risk of stroke. The risk reduction for pioglitazone reached significance (P = .025), but there was no signal of risk reduction for SGLT2i (P = .88) or for DPP4i (P = .5).
Weight Loss Is Potential Mechanism
Looking to explain the protection from stroke associated with some of the newer antidiabetic therapies, Gordon Kelley, MD, who leads the stroke program for AdventHealth Medical Group, Shawnee Mission, Kansas, suggested that weight loss is probably important.
“In our group, we work as a team to manage stroke risk in patients with diabetes, so I am not much involved in the choice of antidiabetic therapies, but it does seem that SGLT2 inhibitors and the GLP-1 receptor agonists share weight loss as an effect beyond glucose control,” he said.
Dr. Goldstein agreed that weight loss is a potential contributor to the cardiovascular benefits of GLP-1RA and SGLT2i, but he indicated that it might not help explain the reduction in stroke, an effect demonstrated repeatedly with GLP-1RA but inconsistently with SGLT2i.
The argument against weight loss as the critical mechanism of stroke prevention from newer antidiabetic drugs is strengthened by studies that suggest weight loss with SGLT2i appears to be even better than on GLP-1RA. In a study published in a pharmacy journal, weight loss was about twice as great among T2DM patients after 6 months of treatment managed with SGLT2i relative to those on a GLP-1RA (-2.8 vs 1.15 kg; P = .014).
Newer Antidiabetic Agents Guideline Recommended
In the 2019 American College of Cardiology/American Heart Association guidelines on the Primary Prevention of Cardiovascular Disease, stroke reduction is not discussed as an isolated risk, but these guidelines do recommend GLP-1RA or SGLT2i after metformin for glycemic control in T2DM patients with atherosclerotic cardiovascular disease (ASCVD) risk factors. This is based on evidence that drugs of both classes reduce risk for ASCVD events. The risk reduction has been particularly strong for heart failure.
For the risk of stroke specifically in patients with T2DM, Dr. Goldstein recommended calculating the ASCVD risk with the simple but well validated ACC risk calculator that is available online and is quickly completed when values for patient risk factors are readily available. For those with greater than 10% risk of an event in the next 10 years, he thinks GLP-1RA are a reasonable choice for prevention of stroke and other ASCVD events.
“GLP-1RA is mentioned in the guidelines, so this is supported,” said Dr. Goldstein, although adding that his choice of this class over SGLT2i is a personal if informed recommendation. He believes that the data favor GLP-1RA even if the exact mechanism of this protection is yet to be identified.
Dr. Goldstein and Dr. Kelley report no potential conflicts of interest.
DENVER —
In patients with type 2 diabetes mellitus (T2DM), the evidence is strong that “they are not working through glycemic control per se,” according to Larry B. Goldstein, MD, chair of neurology, University of Kentucky School of Medicine, Louisville. “But it is not yet clear what the mechanism of benefit is.”
In the past, several large randomized studies, such as the ACCORD trial, provided compelling evidence that tighter glycemic control does not translate into meaningful protection across stroke. Performed before many of the modern therapies were available, this lack of protection was observed with essentially “no heterogeneity across specific drugs,” according to Dr. Goldstein.
In long-term results from ACCORD, published in 2011, the odds ratio for a fatal or nonfatal stroke was a nonsignificant 0.97 in favor of tight glycemic control relative to standard control. The wide confidence intervals ruled out any hint of statistical significance (95% CI, 0.77-1.33; P = .85). Dr. Goldstein provided data from numerous other studies and meta-analyses that drew the same conclusion.
Stroke Prevention With Antidiabetic Drugs
“What has changed is that we have new ways of glycemic control, and some of these do show protection against stroke,” Dr. Goldstein said. Yet, the newer drugs do not do a better job at sustained reductions of HbA1c or other measures of reaching lower blood glucose reductions when adherence is similar.
“The level of glucose control with the newer agents is really about the same,” Dr. Goldstein said at the annual meeting of the American Academy of Neurology, where he led a symposium called Controversies in Stroke Treatment and Prevention.
The newer agents, such as sodium glucose co-transport-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have been associated with significant and clinically meaningful reductions in cardiovascular events. However, it is not clear that even these two medications perform similarly for stroke prevention specifically.
Of these two drug classes, Dr. Goldstein said the evidence most strongly supports GLP-1 receptor agonists. He cited one meta-analysis of eight randomized studies that calculated a risk reduction of about 15% whether calculated for fatal or nonfatal strokes. For each the protection was highly statistically significant (P = .0002 and P < .001, respectively).
In contrast, the effect of SGLT-2 inhibitors is weaker. In a study that distilled data from large cardiovascular trials with GLP-1RA, SGLT2i, dipeptidyl peptidase-4 inhibitors (DPP4i), and pioglitazone, a thiazolidinedione, only GLP-1RA drugs were associated with a highly significant (P < .001) reduction in risk of stroke. The risk reduction for pioglitazone reached significance (P = .025), but there was no signal of risk reduction for SGLT2i (P = .88) or for DPP4i (P = .5).
Weight Loss Is Potential Mechanism
Looking to explain the protection from stroke associated with some of the newer antidiabetic therapies, Gordon Kelley, MD, who leads the stroke program for AdventHealth Medical Group, Shawnee Mission, Kansas, suggested that weight loss is probably important.
“In our group, we work as a team to manage stroke risk in patients with diabetes, so I am not much involved in the choice of antidiabetic therapies, but it does seem that SGLT2 inhibitors and the GLP-1 receptor agonists share weight loss as an effect beyond glucose control,” he said.
Dr. Goldstein agreed that weight loss is a potential contributor to the cardiovascular benefits of GLP-1RA and SGLT2i, but he indicated that it might not help explain the reduction in stroke, an effect demonstrated repeatedly with GLP-1RA but inconsistently with SGLT2i.
The argument against weight loss as the critical mechanism of stroke prevention from newer antidiabetic drugs is strengthened by studies that suggest weight loss with SGLT2i appears to be even better than on GLP-1RA. In a study published in a pharmacy journal, weight loss was about twice as great among T2DM patients after 6 months of treatment managed with SGLT2i relative to those on a GLP-1RA (-2.8 vs 1.15 kg; P = .014).
Newer Antidiabetic Agents Guideline Recommended
In the 2019 American College of Cardiology/American Heart Association guidelines on the Primary Prevention of Cardiovascular Disease, stroke reduction is not discussed as an isolated risk, but these guidelines do recommend GLP-1RA or SGLT2i after metformin for glycemic control in T2DM patients with atherosclerotic cardiovascular disease (ASCVD) risk factors. This is based on evidence that drugs of both classes reduce risk for ASCVD events. The risk reduction has been particularly strong for heart failure.
For the risk of stroke specifically in patients with T2DM, Dr. Goldstein recommended calculating the ASCVD risk with the simple but well validated ACC risk calculator that is available online and is quickly completed when values for patient risk factors are readily available. For those with greater than 10% risk of an event in the next 10 years, he thinks GLP-1RA are a reasonable choice for prevention of stroke and other ASCVD events.
“GLP-1RA is mentioned in the guidelines, so this is supported,” said Dr. Goldstein, although adding that his choice of this class over SGLT2i is a personal if informed recommendation. He believes that the data favor GLP-1RA even if the exact mechanism of this protection is yet to be identified.
Dr. Goldstein and Dr. Kelley report no potential conflicts of interest.
DENVER —
In patients with type 2 diabetes mellitus (T2DM), the evidence is strong that “they are not working through glycemic control per se,” according to Larry B. Goldstein, MD, chair of neurology, University of Kentucky School of Medicine, Louisville. “But it is not yet clear what the mechanism of benefit is.”
In the past, several large randomized studies, such as the ACCORD trial, provided compelling evidence that tighter glycemic control does not translate into meaningful protection across stroke. Performed before many of the modern therapies were available, this lack of protection was observed with essentially “no heterogeneity across specific drugs,” according to Dr. Goldstein.
In long-term results from ACCORD, published in 2011, the odds ratio for a fatal or nonfatal stroke was a nonsignificant 0.97 in favor of tight glycemic control relative to standard control. The wide confidence intervals ruled out any hint of statistical significance (95% CI, 0.77-1.33; P = .85). Dr. Goldstein provided data from numerous other studies and meta-analyses that drew the same conclusion.
Stroke Prevention With Antidiabetic Drugs
“What has changed is that we have new ways of glycemic control, and some of these do show protection against stroke,” Dr. Goldstein said. Yet, the newer drugs do not do a better job at sustained reductions of HbA1c or other measures of reaching lower blood glucose reductions when adherence is similar.
“The level of glucose control with the newer agents is really about the same,” Dr. Goldstein said at the annual meeting of the American Academy of Neurology, where he led a symposium called Controversies in Stroke Treatment and Prevention.
The newer agents, such as sodium glucose co-transport-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have been associated with significant and clinically meaningful reductions in cardiovascular events. However, it is not clear that even these two medications perform similarly for stroke prevention specifically.
Of these two drug classes, Dr. Goldstein said the evidence most strongly supports GLP-1 receptor agonists. He cited one meta-analysis of eight randomized studies that calculated a risk reduction of about 15% whether calculated for fatal or nonfatal strokes. For each the protection was highly statistically significant (P = .0002 and P < .001, respectively).
In contrast, the effect of SGLT-2 inhibitors is weaker. In a study that distilled data from large cardiovascular trials with GLP-1RA, SGLT2i, dipeptidyl peptidase-4 inhibitors (DPP4i), and pioglitazone, a thiazolidinedione, only GLP-1RA drugs were associated with a highly significant (P < .001) reduction in risk of stroke. The risk reduction for pioglitazone reached significance (P = .025), but there was no signal of risk reduction for SGLT2i (P = .88) or for DPP4i (P = .5).
Weight Loss Is Potential Mechanism
Looking to explain the protection from stroke associated with some of the newer antidiabetic therapies, Gordon Kelley, MD, who leads the stroke program for AdventHealth Medical Group, Shawnee Mission, Kansas, suggested that weight loss is probably important.
“In our group, we work as a team to manage stroke risk in patients with diabetes, so I am not much involved in the choice of antidiabetic therapies, but it does seem that SGLT2 inhibitors and the GLP-1 receptor agonists share weight loss as an effect beyond glucose control,” he said.
Dr. Goldstein agreed that weight loss is a potential contributor to the cardiovascular benefits of GLP-1RA and SGLT2i, but he indicated that it might not help explain the reduction in stroke, an effect demonstrated repeatedly with GLP-1RA but inconsistently with SGLT2i.
The argument against weight loss as the critical mechanism of stroke prevention from newer antidiabetic drugs is strengthened by studies that suggest weight loss with SGLT2i appears to be even better than on GLP-1RA. In a study published in a pharmacy journal, weight loss was about twice as great among T2DM patients after 6 months of treatment managed with SGLT2i relative to those on a GLP-1RA (-2.8 vs 1.15 kg; P = .014).
Newer Antidiabetic Agents Guideline Recommended
In the 2019 American College of Cardiology/American Heart Association guidelines on the Primary Prevention of Cardiovascular Disease, stroke reduction is not discussed as an isolated risk, but these guidelines do recommend GLP-1RA or SGLT2i after metformin for glycemic control in T2DM patients with atherosclerotic cardiovascular disease (ASCVD) risk factors. This is based on evidence that drugs of both classes reduce risk for ASCVD events. The risk reduction has been particularly strong for heart failure.
For the risk of stroke specifically in patients with T2DM, Dr. Goldstein recommended calculating the ASCVD risk with the simple but well validated ACC risk calculator that is available online and is quickly completed when values for patient risk factors are readily available. For those with greater than 10% risk of an event in the next 10 years, he thinks GLP-1RA are a reasonable choice for prevention of stroke and other ASCVD events.
“GLP-1RA is mentioned in the guidelines, so this is supported,” said Dr. Goldstein, although adding that his choice of this class over SGLT2i is a personal if informed recommendation. He believes that the data favor GLP-1RA even if the exact mechanism of this protection is yet to be identified.
Dr. Goldstein and Dr. Kelley report no potential conflicts of interest.
FROM AAN 2024
Barcelona’s Best: Vasculitis Treatment Studies on Stopping Steroids, Abatacept, Plasma Exchange, Vaccination
Some of the best clinical trials of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV) that were presented at the 21st International Vasculitis Workshop in Barcelona, Spain, included studies addressing relapse after stopping steroids, preventing relapse with abatacept, improving kidney function with plasma exchange, and vaccinating rituximab-treated patients.
Stopping Steroids After Remission in GPA
In the randomized, open-label TAPIR (The Assessment of Prednisone In Remission Trial) study of 159 adults with GPA in remission who had tapered to a prednisone dose of 5 mg/day, those who remained at that dosage had a significantly lower rate of relapse after 6 months than those who tapered to 0 mg/day (4.2% vs 15.5%; P = .227), according to results reported at the meeting.
However, use of a higher dose of prednisone for disease relapse by 6 months was similar for patients who used rituximab at baseline (8.8% with 0 mg/day vs 6.1% with 5 mg/day; P = .667), and the difference in this primary outcome was more pronounced among patients who did not take rituximab at baseline (20.0% with 0 mg/day vs 2.6% with 5 mg/day; P = .023).
A higher percentage of patients taking prednisone 0 mg/day had disease relapses that were considered minor (14.1% and 4.2%; P = .0391). Major relapses occurred in none of the patients taking 5 mg/day and in 1.4% receiving 0 mg/day. About 90% of patients in either treatment arm completed the trial.
The study, funded by the National Institute of Arthritis and Musculoskelatal and Skin Diseases and the National Heart Lung and Blood Institute, was unique in that half of patients randomized in the study were enrolled at community clinics and half were enrolled at Vasculitis Clinical Research Consortium clinical centers.
Abatacept Falls Short for Preventing Relapse in GPA
Adding abatacept to glucocorticoids failed to reduce risk of relapse, worsening disease, or failure to reach remission in adults with relapsing, nonsevere GPA, based on data from a randomized trial of 65 individuals.
In the 20-site, randomized, double-blind ABROGATE (Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis) study, 34 patients received 125 mg subcutaneous abatacept once a week or a placebo in addition to 30 mg/day of prednisone that was tapered and discontinued after 12 weeks. Patients who were receiving methotrexate, azathioprine, mycophenolate, or leflunomide at baseline continued the medication at a stable dose.
The primary outcome of disease worsening or relapse occurred in 62% of the abatacept group and 68% of the placebo group, and no significant difference in treatment failure rate appeared between the groups. In addition, key secondary endpoints of time to full remission, duration of glucocorticoid-free remission, relapse severity, prevention of damage, and patient-reported quality of life outcomes were not significantly different between the groups.
A total of 112 adverse events occurred, with similar type and severity between the groups, including incidence of infections.
The findings were limited by the relatively small sample size, but the results suggest a need for further research to determine mechanisms of disease and explore additional novel treatments for this rare patient population, the researchers wrote in their abstract.
The study was funded by the National Institutes of Health and Bristol-Myers Squibb.
Plasma Exchange Improves Kidney Function in AAV
Use of therapeutic plasma exchange (PLEX) as an adjunct treatment improved early kidney function in adults with AAV and glomerulonephritis but did not extend beyond 8 weeks, and recovery of kidney function was no different between patients receiving a regular glucocorticoid regimen versus a reduced course, based on a post-hoc analysis of 691 individuals in the international randomized controlled trial called PEXIVAS.
The primary outcomes of change in kidney function based on estimated glomerular filtration rate (eGFR) from baseline over 1 year and the percentage of patients with improvement in eGFR of at least 15 mL/min/1.73 m2 at weeks 12, 26, and 52.
The rate of improved eGFR was significantly greater in the PLEX group, compared with controls, at 2, 4, and 8 weeks. At 4 weeks, significantly more patients in the PLEX group had an increase in eGFR by at least 15 mL/min/1.73 m2, compared with the control group (relative risk [RR], 1.41; P = .008). In addition, improved kidney function within 4 weeks was significantly associated with lower risk of kidney failure within 1 year, regardless of treatment group.
The original PEXIVAS trial was supported by various government institutes and agencies from multiple countries.
Reinforced Vaccine Strategy with Rituximab Improved Antibody Response in AAV
A vaccine strategy consisting of a double dose of 13-valent antipneumococcal conjugate vaccine (PCV13) at day 0 and day 7 followed by a single dose of 23-valent unconjugated pneumococcal polysaccharide vaccine (PPV23) at 5 months significantly improved antibody responses against Streptococcus pneumoniae in patients with AAV, compared with standard treatment, based on data from 95 individuals in the multicenter, open-label study called PNEUMOVAS.
Adults with newly diagnosed AAV were randomly assigned to one of three treatment arms: a standard regimen of one dose of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 1); a double dose of PCV13 at day 0 and day 7 with a dose of PPV23 at month 5 (arm 2); or four doses of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 3). These patients received PCV13 within 2 days before or after their first infusion of rituximab.
The primary endpoint was positive antibody response against 12 pneumococcal subtypes common to the PCV13 and PCV23 vaccines at 6 months. At 6 months, the immune response to 0-3, 4-6, 7-9, or 10-12 serotypes was 83.3%, 13.3%, 3.3%, and 0%, respectively, in arm 1; 56.3%, 28.1%, 15.6%, and 0% in arm 2; and 60.6%, 33.3%, 6.1%, and 0% in arm 3.
No severe adverse events related to vaccination were observed in any of the groups; a total of eight AAV flares occurred in six patients (one in arm 1, two in arm 2, and three in arm 3). Local and systemic reactions occurred more frequently with the reinforced dose regimens, but these were mostly grade 1 or 2 local reactions.
The study was supported by the French Ministry of Health.
Some of the best clinical trials of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV) that were presented at the 21st International Vasculitis Workshop in Barcelona, Spain, included studies addressing relapse after stopping steroids, preventing relapse with abatacept, improving kidney function with plasma exchange, and vaccinating rituximab-treated patients.
Stopping Steroids After Remission in GPA
In the randomized, open-label TAPIR (The Assessment of Prednisone In Remission Trial) study of 159 adults with GPA in remission who had tapered to a prednisone dose of 5 mg/day, those who remained at that dosage had a significantly lower rate of relapse after 6 months than those who tapered to 0 mg/day (4.2% vs 15.5%; P = .227), according to results reported at the meeting.
However, use of a higher dose of prednisone for disease relapse by 6 months was similar for patients who used rituximab at baseline (8.8% with 0 mg/day vs 6.1% with 5 mg/day; P = .667), and the difference in this primary outcome was more pronounced among patients who did not take rituximab at baseline (20.0% with 0 mg/day vs 2.6% with 5 mg/day; P = .023).
A higher percentage of patients taking prednisone 0 mg/day had disease relapses that were considered minor (14.1% and 4.2%; P = .0391). Major relapses occurred in none of the patients taking 5 mg/day and in 1.4% receiving 0 mg/day. About 90% of patients in either treatment arm completed the trial.
The study, funded by the National Institute of Arthritis and Musculoskelatal and Skin Diseases and the National Heart Lung and Blood Institute, was unique in that half of patients randomized in the study were enrolled at community clinics and half were enrolled at Vasculitis Clinical Research Consortium clinical centers.
Abatacept Falls Short for Preventing Relapse in GPA
Adding abatacept to glucocorticoids failed to reduce risk of relapse, worsening disease, or failure to reach remission in adults with relapsing, nonsevere GPA, based on data from a randomized trial of 65 individuals.
In the 20-site, randomized, double-blind ABROGATE (Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis) study, 34 patients received 125 mg subcutaneous abatacept once a week or a placebo in addition to 30 mg/day of prednisone that was tapered and discontinued after 12 weeks. Patients who were receiving methotrexate, azathioprine, mycophenolate, or leflunomide at baseline continued the medication at a stable dose.
The primary outcome of disease worsening or relapse occurred in 62% of the abatacept group and 68% of the placebo group, and no significant difference in treatment failure rate appeared between the groups. In addition, key secondary endpoints of time to full remission, duration of glucocorticoid-free remission, relapse severity, prevention of damage, and patient-reported quality of life outcomes were not significantly different between the groups.
A total of 112 adverse events occurred, with similar type and severity between the groups, including incidence of infections.
The findings were limited by the relatively small sample size, but the results suggest a need for further research to determine mechanisms of disease and explore additional novel treatments for this rare patient population, the researchers wrote in their abstract.
The study was funded by the National Institutes of Health and Bristol-Myers Squibb.
Plasma Exchange Improves Kidney Function in AAV
Use of therapeutic plasma exchange (PLEX) as an adjunct treatment improved early kidney function in adults with AAV and glomerulonephritis but did not extend beyond 8 weeks, and recovery of kidney function was no different between patients receiving a regular glucocorticoid regimen versus a reduced course, based on a post-hoc analysis of 691 individuals in the international randomized controlled trial called PEXIVAS.
The primary outcomes of change in kidney function based on estimated glomerular filtration rate (eGFR) from baseline over 1 year and the percentage of patients with improvement in eGFR of at least 15 mL/min/1.73 m2 at weeks 12, 26, and 52.
The rate of improved eGFR was significantly greater in the PLEX group, compared with controls, at 2, 4, and 8 weeks. At 4 weeks, significantly more patients in the PLEX group had an increase in eGFR by at least 15 mL/min/1.73 m2, compared with the control group (relative risk [RR], 1.41; P = .008). In addition, improved kidney function within 4 weeks was significantly associated with lower risk of kidney failure within 1 year, regardless of treatment group.
The original PEXIVAS trial was supported by various government institutes and agencies from multiple countries.
Reinforced Vaccine Strategy with Rituximab Improved Antibody Response in AAV
A vaccine strategy consisting of a double dose of 13-valent antipneumococcal conjugate vaccine (PCV13) at day 0 and day 7 followed by a single dose of 23-valent unconjugated pneumococcal polysaccharide vaccine (PPV23) at 5 months significantly improved antibody responses against Streptococcus pneumoniae in patients with AAV, compared with standard treatment, based on data from 95 individuals in the multicenter, open-label study called PNEUMOVAS.
Adults with newly diagnosed AAV were randomly assigned to one of three treatment arms: a standard regimen of one dose of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 1); a double dose of PCV13 at day 0 and day 7 with a dose of PPV23 at month 5 (arm 2); or four doses of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 3). These patients received PCV13 within 2 days before or after their first infusion of rituximab.
The primary endpoint was positive antibody response against 12 pneumococcal subtypes common to the PCV13 and PCV23 vaccines at 6 months. At 6 months, the immune response to 0-3, 4-6, 7-9, or 10-12 serotypes was 83.3%, 13.3%, 3.3%, and 0%, respectively, in arm 1; 56.3%, 28.1%, 15.6%, and 0% in arm 2; and 60.6%, 33.3%, 6.1%, and 0% in arm 3.
No severe adverse events related to vaccination were observed in any of the groups; a total of eight AAV flares occurred in six patients (one in arm 1, two in arm 2, and three in arm 3). Local and systemic reactions occurred more frequently with the reinforced dose regimens, but these were mostly grade 1 or 2 local reactions.
The study was supported by the French Ministry of Health.
Some of the best clinical trials of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV) that were presented at the 21st International Vasculitis Workshop in Barcelona, Spain, included studies addressing relapse after stopping steroids, preventing relapse with abatacept, improving kidney function with plasma exchange, and vaccinating rituximab-treated patients.
Stopping Steroids After Remission in GPA
In the randomized, open-label TAPIR (The Assessment of Prednisone In Remission Trial) study of 159 adults with GPA in remission who had tapered to a prednisone dose of 5 mg/day, those who remained at that dosage had a significantly lower rate of relapse after 6 months than those who tapered to 0 mg/day (4.2% vs 15.5%; P = .227), according to results reported at the meeting.
However, use of a higher dose of prednisone for disease relapse by 6 months was similar for patients who used rituximab at baseline (8.8% with 0 mg/day vs 6.1% with 5 mg/day; P = .667), and the difference in this primary outcome was more pronounced among patients who did not take rituximab at baseline (20.0% with 0 mg/day vs 2.6% with 5 mg/day; P = .023).
A higher percentage of patients taking prednisone 0 mg/day had disease relapses that were considered minor (14.1% and 4.2%; P = .0391). Major relapses occurred in none of the patients taking 5 mg/day and in 1.4% receiving 0 mg/day. About 90% of patients in either treatment arm completed the trial.
The study, funded by the National Institute of Arthritis and Musculoskelatal and Skin Diseases and the National Heart Lung and Blood Institute, was unique in that half of patients randomized in the study were enrolled at community clinics and half were enrolled at Vasculitis Clinical Research Consortium clinical centers.
Abatacept Falls Short for Preventing Relapse in GPA
Adding abatacept to glucocorticoids failed to reduce risk of relapse, worsening disease, or failure to reach remission in adults with relapsing, nonsevere GPA, based on data from a randomized trial of 65 individuals.
In the 20-site, randomized, double-blind ABROGATE (Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis) study, 34 patients received 125 mg subcutaneous abatacept once a week or a placebo in addition to 30 mg/day of prednisone that was tapered and discontinued after 12 weeks. Patients who were receiving methotrexate, azathioprine, mycophenolate, or leflunomide at baseline continued the medication at a stable dose.
The primary outcome of disease worsening or relapse occurred in 62% of the abatacept group and 68% of the placebo group, and no significant difference in treatment failure rate appeared between the groups. In addition, key secondary endpoints of time to full remission, duration of glucocorticoid-free remission, relapse severity, prevention of damage, and patient-reported quality of life outcomes were not significantly different between the groups.
A total of 112 adverse events occurred, with similar type and severity between the groups, including incidence of infections.
The findings were limited by the relatively small sample size, but the results suggest a need for further research to determine mechanisms of disease and explore additional novel treatments for this rare patient population, the researchers wrote in their abstract.
The study was funded by the National Institutes of Health and Bristol-Myers Squibb.
Plasma Exchange Improves Kidney Function in AAV
Use of therapeutic plasma exchange (PLEX) as an adjunct treatment improved early kidney function in adults with AAV and glomerulonephritis but did not extend beyond 8 weeks, and recovery of kidney function was no different between patients receiving a regular glucocorticoid regimen versus a reduced course, based on a post-hoc analysis of 691 individuals in the international randomized controlled trial called PEXIVAS.
The primary outcomes of change in kidney function based on estimated glomerular filtration rate (eGFR) from baseline over 1 year and the percentage of patients with improvement in eGFR of at least 15 mL/min/1.73 m2 at weeks 12, 26, and 52.
The rate of improved eGFR was significantly greater in the PLEX group, compared with controls, at 2, 4, and 8 weeks. At 4 weeks, significantly more patients in the PLEX group had an increase in eGFR by at least 15 mL/min/1.73 m2, compared with the control group (relative risk [RR], 1.41; P = .008). In addition, improved kidney function within 4 weeks was significantly associated with lower risk of kidney failure within 1 year, regardless of treatment group.
The original PEXIVAS trial was supported by various government institutes and agencies from multiple countries.
Reinforced Vaccine Strategy with Rituximab Improved Antibody Response in AAV
A vaccine strategy consisting of a double dose of 13-valent antipneumococcal conjugate vaccine (PCV13) at day 0 and day 7 followed by a single dose of 23-valent unconjugated pneumococcal polysaccharide vaccine (PPV23) at 5 months significantly improved antibody responses against Streptococcus pneumoniae in patients with AAV, compared with standard treatment, based on data from 95 individuals in the multicenter, open-label study called PNEUMOVAS.
Adults with newly diagnosed AAV were randomly assigned to one of three treatment arms: a standard regimen of one dose of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 1); a double dose of PCV13 at day 0 and day 7 with a dose of PPV23 at month 5 (arm 2); or four doses of PCV13 at day 0 and one dose of PPV23 at month 5 (arm 3). These patients received PCV13 within 2 days before or after their first infusion of rituximab.
The primary endpoint was positive antibody response against 12 pneumococcal subtypes common to the PCV13 and PCV23 vaccines at 6 months. At 6 months, the immune response to 0-3, 4-6, 7-9, or 10-12 serotypes was 83.3%, 13.3%, 3.3%, and 0%, respectively, in arm 1; 56.3%, 28.1%, 15.6%, and 0% in arm 2; and 60.6%, 33.3%, 6.1%, and 0% in arm 3.
No severe adverse events related to vaccination were observed in any of the groups; a total of eight AAV flares occurred in six patients (one in arm 1, two in arm 2, and three in arm 3). Local and systemic reactions occurred more frequently with the reinforced dose regimens, but these were mostly grade 1 or 2 local reactions.
The study was supported by the French Ministry of Health.
How Medicare Reimbursement Trends Could Affect Breast Surgeries
These were findings of new research presented by Terry P. Gao, MD, at the American Society of Breast Surgeons annual meeting.
Medicare reimbursements often set a benchmark that is followed by private insurers, and the impact of changes on various breast surgeries have not been examined, Dr. Gao, a research resident at Temple University Hospital, Philadelphia, said during a press briefing in advance of the meeting.
“This study is important because it is the first to analyze trends in Medicare reimbursement for breast cancer surgery over a long period,” Dr. Gao said during an interview. The findings highlight a critical issue that could impact access to quality care, especially for vulnerable populations, she said.
How Were the Data Analyzed?
Dr. Gao and colleagues reviewed percent changes in reimbursement procedures over a 20-year period and compared them to changes in the consumer price index (CPI) to show the real-life impact of inflation.
The study examined reimbursements based on the Medicare Physician Fee Schedule Look-Up Tool from 2003 to 2023 for 10 procedures. The procedures were core needle biopsy, open incisional breast biopsy, open excisional breast biopsy, lumpectomy, lumpectomy with axillary lymph node dissection (ALND), simple mastectomy, radical mastectomy, modified radical mastectomy, biopsy/removal of lymph nodes, and sentinel lymph node biopsy.
What Does the New Study Show?
“Reimbursements did not keep pace with the price of goods and services,” Dr. Gao said during the press briefing.
After the researchers corrected data for inflation, the overall mean Medicare reimbursement for breast cancer surgeries decreased by approximately 21%, based in part on the 69% increase in the CPI over the study period, Dr. Gao said. The greatest change was in core needle biopsy, for which reimbursement decreased by 36%.
After inflation adjustment, reimbursement increases were seen for only two procedures, lumpectomy and simple mastectomy, of 0.37% and 3.58%, respectively, but these do not represent meaningful gains, Dr. Gao said.
The researchers also used a model to estimate the real-life impact of decreased reimbursement on clinicians. They subtracted the actual 2023 compensation from expected 2023 compensation based on inflation for a breast cancer case incidence of 297,790 patients who underwent axillary surgery, breast lumpectomy, or simple mastectomy. The calculated potential real-world compensation loss for that year was $107,604,444.
What are the Clinical Implications?
The current study is the first to put specific numbers on the trend in declining breast cancer payments, and the findings should encourage physicians to advocate for equitable policies, Dr. Gao noted during the briefing.
The substantial decrease in inflation-adjusted reimbursement rates was significant, she said during the interview. Although the decrease reflects similar trends seen in other specialties, the magnitude is a potential cause for concern, she said.
Declining reimbursements could disproportionately hurt safety-net hospitals serving vulnerable populations by limiting their ability to invest in better care and potentially worsening existing racial disparities, Dr. Gao told this publication. “Additionally, surgeons may opt out of Medicare networks due to low rates, leading to access issues and longer wait times. Finally, these trends could discourage future generations from specializing in breast cancer surgery.”
The study findings should be considered in the context of the complex and rapidly changing clinical landscape in which breast cancer care is evolving, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said during an interview.
“Surgery remains a critically important aspect to curative treatment,” Dr. Teshome said.
Surgical decision-making tailored to each patient’s goals involves coordination from a multidisciplinary team as well as skill and attention from surgeons, she added.
“This degree of specialization and nuance is not always captured in reimbursement models for breast surgery,” Dr. Teshome emphasized. The policy implications of any changes in Medicare reimbursement will be important given the American Cancer Society reports breast cancer as the most commonly diagnosed cancer in women in the United States, and as the second leading cause of cancer death in US women, she noted.
What Additional Research Is Needed?
Research is needed to understand how declining reimbursements affect patients’ access to care, treatment choices, and long-term outcomes, Dr. Gao said in the interview. Future studies also are needed to examine provider overhead costs, staffing structures, and profit margins to offer a more comprehensive understanding of financial sustainability.
Dr. Gao and Dr. Teshome had no financial conflicts to disclose.
These were findings of new research presented by Terry P. Gao, MD, at the American Society of Breast Surgeons annual meeting.
Medicare reimbursements often set a benchmark that is followed by private insurers, and the impact of changes on various breast surgeries have not been examined, Dr. Gao, a research resident at Temple University Hospital, Philadelphia, said during a press briefing in advance of the meeting.
“This study is important because it is the first to analyze trends in Medicare reimbursement for breast cancer surgery over a long period,” Dr. Gao said during an interview. The findings highlight a critical issue that could impact access to quality care, especially for vulnerable populations, she said.
How Were the Data Analyzed?
Dr. Gao and colleagues reviewed percent changes in reimbursement procedures over a 20-year period and compared them to changes in the consumer price index (CPI) to show the real-life impact of inflation.
The study examined reimbursements based on the Medicare Physician Fee Schedule Look-Up Tool from 2003 to 2023 for 10 procedures. The procedures were core needle biopsy, open incisional breast biopsy, open excisional breast biopsy, lumpectomy, lumpectomy with axillary lymph node dissection (ALND), simple mastectomy, radical mastectomy, modified radical mastectomy, biopsy/removal of lymph nodes, and sentinel lymph node biopsy.
What Does the New Study Show?
“Reimbursements did not keep pace with the price of goods and services,” Dr. Gao said during the press briefing.
After the researchers corrected data for inflation, the overall mean Medicare reimbursement for breast cancer surgeries decreased by approximately 21%, based in part on the 69% increase in the CPI over the study period, Dr. Gao said. The greatest change was in core needle biopsy, for which reimbursement decreased by 36%.
After inflation adjustment, reimbursement increases were seen for only two procedures, lumpectomy and simple mastectomy, of 0.37% and 3.58%, respectively, but these do not represent meaningful gains, Dr. Gao said.
The researchers also used a model to estimate the real-life impact of decreased reimbursement on clinicians. They subtracted the actual 2023 compensation from expected 2023 compensation based on inflation for a breast cancer case incidence of 297,790 patients who underwent axillary surgery, breast lumpectomy, or simple mastectomy. The calculated potential real-world compensation loss for that year was $107,604,444.
What are the Clinical Implications?
The current study is the first to put specific numbers on the trend in declining breast cancer payments, and the findings should encourage physicians to advocate for equitable policies, Dr. Gao noted during the briefing.
The substantial decrease in inflation-adjusted reimbursement rates was significant, she said during the interview. Although the decrease reflects similar trends seen in other specialties, the magnitude is a potential cause for concern, she said.
Declining reimbursements could disproportionately hurt safety-net hospitals serving vulnerable populations by limiting their ability to invest in better care and potentially worsening existing racial disparities, Dr. Gao told this publication. “Additionally, surgeons may opt out of Medicare networks due to low rates, leading to access issues and longer wait times. Finally, these trends could discourage future generations from specializing in breast cancer surgery.”
The study findings should be considered in the context of the complex and rapidly changing clinical landscape in which breast cancer care is evolving, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said during an interview.
“Surgery remains a critically important aspect to curative treatment,” Dr. Teshome said.
Surgical decision-making tailored to each patient’s goals involves coordination from a multidisciplinary team as well as skill and attention from surgeons, she added.
“This degree of specialization and nuance is not always captured in reimbursement models for breast surgery,” Dr. Teshome emphasized. The policy implications of any changes in Medicare reimbursement will be important given the American Cancer Society reports breast cancer as the most commonly diagnosed cancer in women in the United States, and as the second leading cause of cancer death in US women, she noted.
What Additional Research Is Needed?
Research is needed to understand how declining reimbursements affect patients’ access to care, treatment choices, and long-term outcomes, Dr. Gao said in the interview. Future studies also are needed to examine provider overhead costs, staffing structures, and profit margins to offer a more comprehensive understanding of financial sustainability.
Dr. Gao and Dr. Teshome had no financial conflicts to disclose.
These were findings of new research presented by Terry P. Gao, MD, at the American Society of Breast Surgeons annual meeting.
Medicare reimbursements often set a benchmark that is followed by private insurers, and the impact of changes on various breast surgeries have not been examined, Dr. Gao, a research resident at Temple University Hospital, Philadelphia, said during a press briefing in advance of the meeting.
“This study is important because it is the first to analyze trends in Medicare reimbursement for breast cancer surgery over a long period,” Dr. Gao said during an interview. The findings highlight a critical issue that could impact access to quality care, especially for vulnerable populations, she said.
How Were the Data Analyzed?
Dr. Gao and colleagues reviewed percent changes in reimbursement procedures over a 20-year period and compared them to changes in the consumer price index (CPI) to show the real-life impact of inflation.
The study examined reimbursements based on the Medicare Physician Fee Schedule Look-Up Tool from 2003 to 2023 for 10 procedures. The procedures were core needle biopsy, open incisional breast biopsy, open excisional breast biopsy, lumpectomy, lumpectomy with axillary lymph node dissection (ALND), simple mastectomy, radical mastectomy, modified radical mastectomy, biopsy/removal of lymph nodes, and sentinel lymph node biopsy.
What Does the New Study Show?
“Reimbursements did not keep pace with the price of goods and services,” Dr. Gao said during the press briefing.
After the researchers corrected data for inflation, the overall mean Medicare reimbursement for breast cancer surgeries decreased by approximately 21%, based in part on the 69% increase in the CPI over the study period, Dr. Gao said. The greatest change was in core needle biopsy, for which reimbursement decreased by 36%.
After inflation adjustment, reimbursement increases were seen for only two procedures, lumpectomy and simple mastectomy, of 0.37% and 3.58%, respectively, but these do not represent meaningful gains, Dr. Gao said.
The researchers also used a model to estimate the real-life impact of decreased reimbursement on clinicians. They subtracted the actual 2023 compensation from expected 2023 compensation based on inflation for a breast cancer case incidence of 297,790 patients who underwent axillary surgery, breast lumpectomy, or simple mastectomy. The calculated potential real-world compensation loss for that year was $107,604,444.
What are the Clinical Implications?
The current study is the first to put specific numbers on the trend in declining breast cancer payments, and the findings should encourage physicians to advocate for equitable policies, Dr. Gao noted during the briefing.
The substantial decrease in inflation-adjusted reimbursement rates was significant, she said during the interview. Although the decrease reflects similar trends seen in other specialties, the magnitude is a potential cause for concern, she said.
Declining reimbursements could disproportionately hurt safety-net hospitals serving vulnerable populations by limiting their ability to invest in better care and potentially worsening existing racial disparities, Dr. Gao told this publication. “Additionally, surgeons may opt out of Medicare networks due to low rates, leading to access issues and longer wait times. Finally, these trends could discourage future generations from specializing in breast cancer surgery.”
The study findings should be considered in the context of the complex and rapidly changing clinical landscape in which breast cancer care is evolving, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said during an interview.
“Surgery remains a critically important aspect to curative treatment,” Dr. Teshome said.
Surgical decision-making tailored to each patient’s goals involves coordination from a multidisciplinary team as well as skill and attention from surgeons, she added.
“This degree of specialization and nuance is not always captured in reimbursement models for breast surgery,” Dr. Teshome emphasized. The policy implications of any changes in Medicare reimbursement will be important given the American Cancer Society reports breast cancer as the most commonly diagnosed cancer in women in the United States, and as the second leading cause of cancer death in US women, she noted.
What Additional Research Is Needed?
Research is needed to understand how declining reimbursements affect patients’ access to care, treatment choices, and long-term outcomes, Dr. Gao said in the interview. Future studies also are needed to examine provider overhead costs, staffing structures, and profit margins to offer a more comprehensive understanding of financial sustainability.
Dr. Gao and Dr. Teshome had no financial conflicts to disclose.
FROM THE AMERICAN SOCIETY OF BREAST SURGEONS ANNUAL MEETING
Environmental Chemicals Linked to Parkinson’s Disease in Urban Areas
DENVER — , according to results from a new nationwide analysis of a Medicare population.
TCE has long been used as an industrial solvent, and it is a component of several household cleaning products. Case reports have suggested that workers exposed to it have increased risk of Parkinson’s disease, with risk increases as high as 500%.
Exposure can come through air or water, but 97% of environmental TCE is found in the air, according to Brittany Krzyzanowski, PhD, who presented the study at the 2024 annual meeting of the American Academy of Neurology.
Previous studies of TCE had looked primarily at occupational exposure, such as workers at TCE-emitting facilities, or soldiers stationed at Camp Lejeune in North Carolina, where levels of TCE were more than 70-fold higher than EPA-permissible levels. A recent study found a 70% increase in risk of Parkinson’s disease associated with individuals who were stationed there.
From Population Data to Individual Risk
In an interview, Dr. Krzyzanowski pointed out that the Camp Lejeune studies didn’t assign TCE exposure to individuals — instead, researchers noted whether an individual was stationed at that base or another. “Our study adds to the previous work by investigating environmental exposure using TCE estimates that we are able to assign to individuals. [It shows that] you don’t have to work in a facility with TCE, you don’t have to be stationed on a military base with tainted water, you just have to live in a census tract with higher levels of TCE to have increased risk,” said Dr. Krzyzanowski, a research assistant professor at Barrow Neurological Institute in Phoenix.
In the new study, Dr. Krzyzanowski and her colleagues analyzed data from 1,559,135 Medicare beneficiaries with no other health coverage, who had a valid US ZIP code. There were 252,700 incident cases of Parkinson’s disease who were initially diagnosed between 2016 and 2018. These individuals were matched 1:5 with 1,306,435 healthy controls.
Airborne TCE exposure data was drawn the Environmental Protection Agency’s National Air Toxics Assessment data from 2005, about 12 years prior to the start of the study and in line with the expected latency between exposure and development of Parkinson’s disease.
“We found a nationwide association between airborne TCE exposure and Parkinson’s disease risks, but this was only true for the metropolitan areas. Within these metro areas, there was a dose-response effect, where increasing levels of TCE were associated with increasing risk of Parkinson’s disease. In particular, those living in the metros with the highest levels of TCE had a 24% greater risk of Parkinson’s compared with those in metros with the lowest levels of TCE,” Dr. Krzyzanowski said during her presentation. The P-value for the trend was less than .0001.
The census tracts in metropolitan areas are smaller than those in rural areas because of differences in population density, and this leads to greater precision of TCE exposure estimates in urban environments, according to Dr. Krzyzanowski, and this could explain the lack of a statistically significant association seen among rural populations.
‘More Substantial’ Data Adds to Previous Evidence
The new study is an important addition to the literature examining TCE exposure and Parkinson’s disease, according to session moderator Jeff Bronstein, MD, PhD, who was asked for comment. “It’s more substantial data making that association between TCE and Parkinson’s. It’s been growing over the past decade, and this is a more objective, big data association, so it adds more strength to the body of knowledge that we already have. It’s unbiased, which is nice,” said Dr. Bronstein, professor of neurology and director of movement disorders at UCLA.
It remains uncertain whether TCE is a direct cause of Parkinson’s disease, but “a lot of us believe it’s causal. There’s a lot of evidence now. There are some very good studies with inhalation models that show it affects autophagy, or the way we break down proteins, and that it also involves LRRK2 [leucine-rich repeat kinase 2], which is one of the proteins involved in some of the genetic forms [of Parkinson’s disease], and it might affect mitochondria. They’re all linked in network and right now the animal studies point to that network,” said Dr. Bronstein.
Dr. Krzyzanowski has no relevant financial disclosures. Dr. Bronstein consults for a legal firm involved in the Camp Lejeune litigation.
DENVER — , according to results from a new nationwide analysis of a Medicare population.
TCE has long been used as an industrial solvent, and it is a component of several household cleaning products. Case reports have suggested that workers exposed to it have increased risk of Parkinson’s disease, with risk increases as high as 500%.
Exposure can come through air or water, but 97% of environmental TCE is found in the air, according to Brittany Krzyzanowski, PhD, who presented the study at the 2024 annual meeting of the American Academy of Neurology.
Previous studies of TCE had looked primarily at occupational exposure, such as workers at TCE-emitting facilities, or soldiers stationed at Camp Lejeune in North Carolina, where levels of TCE were more than 70-fold higher than EPA-permissible levels. A recent study found a 70% increase in risk of Parkinson’s disease associated with individuals who were stationed there.
From Population Data to Individual Risk
In an interview, Dr. Krzyzanowski pointed out that the Camp Lejeune studies didn’t assign TCE exposure to individuals — instead, researchers noted whether an individual was stationed at that base or another. “Our study adds to the previous work by investigating environmental exposure using TCE estimates that we are able to assign to individuals. [It shows that] you don’t have to work in a facility with TCE, you don’t have to be stationed on a military base with tainted water, you just have to live in a census tract with higher levels of TCE to have increased risk,” said Dr. Krzyzanowski, a research assistant professor at Barrow Neurological Institute in Phoenix.
In the new study, Dr. Krzyzanowski and her colleagues analyzed data from 1,559,135 Medicare beneficiaries with no other health coverage, who had a valid US ZIP code. There were 252,700 incident cases of Parkinson’s disease who were initially diagnosed between 2016 and 2018. These individuals were matched 1:5 with 1,306,435 healthy controls.
Airborne TCE exposure data was drawn the Environmental Protection Agency’s National Air Toxics Assessment data from 2005, about 12 years prior to the start of the study and in line with the expected latency between exposure and development of Parkinson’s disease.
“We found a nationwide association between airborne TCE exposure and Parkinson’s disease risks, but this was only true for the metropolitan areas. Within these metro areas, there was a dose-response effect, where increasing levels of TCE were associated with increasing risk of Parkinson’s disease. In particular, those living in the metros with the highest levels of TCE had a 24% greater risk of Parkinson’s compared with those in metros with the lowest levels of TCE,” Dr. Krzyzanowski said during her presentation. The P-value for the trend was less than .0001.
The census tracts in metropolitan areas are smaller than those in rural areas because of differences in population density, and this leads to greater precision of TCE exposure estimates in urban environments, according to Dr. Krzyzanowski, and this could explain the lack of a statistically significant association seen among rural populations.
‘More Substantial’ Data Adds to Previous Evidence
The new study is an important addition to the literature examining TCE exposure and Parkinson’s disease, according to session moderator Jeff Bronstein, MD, PhD, who was asked for comment. “It’s more substantial data making that association between TCE and Parkinson’s. It’s been growing over the past decade, and this is a more objective, big data association, so it adds more strength to the body of knowledge that we already have. It’s unbiased, which is nice,” said Dr. Bronstein, professor of neurology and director of movement disorders at UCLA.
It remains uncertain whether TCE is a direct cause of Parkinson’s disease, but “a lot of us believe it’s causal. There’s a lot of evidence now. There are some very good studies with inhalation models that show it affects autophagy, or the way we break down proteins, and that it also involves LRRK2 [leucine-rich repeat kinase 2], which is one of the proteins involved in some of the genetic forms [of Parkinson’s disease], and it might affect mitochondria. They’re all linked in network and right now the animal studies point to that network,” said Dr. Bronstein.
Dr. Krzyzanowski has no relevant financial disclosures. Dr. Bronstein consults for a legal firm involved in the Camp Lejeune litigation.
DENVER — , according to results from a new nationwide analysis of a Medicare population.
TCE has long been used as an industrial solvent, and it is a component of several household cleaning products. Case reports have suggested that workers exposed to it have increased risk of Parkinson’s disease, with risk increases as high as 500%.
Exposure can come through air or water, but 97% of environmental TCE is found in the air, according to Brittany Krzyzanowski, PhD, who presented the study at the 2024 annual meeting of the American Academy of Neurology.
Previous studies of TCE had looked primarily at occupational exposure, such as workers at TCE-emitting facilities, or soldiers stationed at Camp Lejeune in North Carolina, where levels of TCE were more than 70-fold higher than EPA-permissible levels. A recent study found a 70% increase in risk of Parkinson’s disease associated with individuals who were stationed there.
From Population Data to Individual Risk
In an interview, Dr. Krzyzanowski pointed out that the Camp Lejeune studies didn’t assign TCE exposure to individuals — instead, researchers noted whether an individual was stationed at that base or another. “Our study adds to the previous work by investigating environmental exposure using TCE estimates that we are able to assign to individuals. [It shows that] you don’t have to work in a facility with TCE, you don’t have to be stationed on a military base with tainted water, you just have to live in a census tract with higher levels of TCE to have increased risk,” said Dr. Krzyzanowski, a research assistant professor at Barrow Neurological Institute in Phoenix.
In the new study, Dr. Krzyzanowski and her colleagues analyzed data from 1,559,135 Medicare beneficiaries with no other health coverage, who had a valid US ZIP code. There were 252,700 incident cases of Parkinson’s disease who were initially diagnosed between 2016 and 2018. These individuals were matched 1:5 with 1,306,435 healthy controls.
Airborne TCE exposure data was drawn the Environmental Protection Agency’s National Air Toxics Assessment data from 2005, about 12 years prior to the start of the study and in line with the expected latency between exposure and development of Parkinson’s disease.
“We found a nationwide association between airborne TCE exposure and Parkinson’s disease risks, but this was only true for the metropolitan areas. Within these metro areas, there was a dose-response effect, where increasing levels of TCE were associated with increasing risk of Parkinson’s disease. In particular, those living in the metros with the highest levels of TCE had a 24% greater risk of Parkinson’s compared with those in metros with the lowest levels of TCE,” Dr. Krzyzanowski said during her presentation. The P-value for the trend was less than .0001.
The census tracts in metropolitan areas are smaller than those in rural areas because of differences in population density, and this leads to greater precision of TCE exposure estimates in urban environments, according to Dr. Krzyzanowski, and this could explain the lack of a statistically significant association seen among rural populations.
‘More Substantial’ Data Adds to Previous Evidence
The new study is an important addition to the literature examining TCE exposure and Parkinson’s disease, according to session moderator Jeff Bronstein, MD, PhD, who was asked for comment. “It’s more substantial data making that association between TCE and Parkinson’s. It’s been growing over the past decade, and this is a more objective, big data association, so it adds more strength to the body of knowledge that we already have. It’s unbiased, which is nice,” said Dr. Bronstein, professor of neurology and director of movement disorders at UCLA.
It remains uncertain whether TCE is a direct cause of Parkinson’s disease, but “a lot of us believe it’s causal. There’s a lot of evidence now. There are some very good studies with inhalation models that show it affects autophagy, or the way we break down proteins, and that it also involves LRRK2 [leucine-rich repeat kinase 2], which is one of the proteins involved in some of the genetic forms [of Parkinson’s disease], and it might affect mitochondria. They’re all linked in network and right now the animal studies point to that network,” said Dr. Bronstein.
Dr. Krzyzanowski has no relevant financial disclosures. Dr. Bronstein consults for a legal firm involved in the Camp Lejeune litigation.
FROM AAN 2024