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Expert calls for more ‘ethnocentric’ research in MS
DALLAS – The way Lilyana Amezcua, MD, sees it, researchers should look beyond using race and ethnicity only as demographic variables when reporting results from multiple sclerosis studies.
“As a demographic variable we see it all the time: white versus non-white, and the methods to arrive at a category are seldom discussed,” Dr. Amezcua said at a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis. “We need to think about ethnocentric research, where the method for determination for race and ethnicity becomes important. This includes examining self-identity (ethnicity), along with physical characteristics and medical records, and confirming that beyond the individual.”
The goal, she continued, is to identify who is at risk for inferior health, such as trying to sort out biological and genetic explanations from non-biological explanations. Ethnocentric research also helps to address health care disparities. “But there’s a broad intersection between race and ethnicity, and depending on the question, genetic ancestry could help,” said Dr. Amezcua, a neurologist at the Keck School of Medicine at the University of Southern California, Los Angeles. “Race tries to infer biological differences, ethnicity infers societal differences, and ancestry infers genetic variations.”
While genetic and biologic features are often used to evaluate how race and ethnicity affects those with MS, Dr. Amezcua noted that several additional factors could influence outcomes. These include access to care as well as individual and community factors that relate to social determinants of health, such as poverty, exposures, and environmental stress. “These could be contributing to worse outcomes,” she said. “So could modifiable factors such as illness beliefs, health literacy, illness management, and acculturation.”
In terms of health literacy, there are reports suggesting that there is a general lack of adequate education and understanding about MS treatment and realistic expectations in African Americans and Hispanics, she said.
In addition, research has shown there is a lower probability of being under the care of a neurologist if you lack health insurance (odds ratio = 0.38) or are African American (OR = 0.52) or Hispanic (OR = 0.61), based on nationally representative data from the 2006-2013 Medical Expenditure Panel Survey (Neurology. 2017;88[24]:2268-75). “Just being African American or Hispanic lowered the probability of seeing a neurologist,” she said.
Published evidence also exists to suggest that illness beliefs drive some people away from MS treatment. “These are beliefs embedded in social and cultural factors known as cultural idioms,” Dr. Amezcua explained. “In a study that was able to capture qualitative and quantitative data, researchers found that social and cultural factors were more frequently reported in immigrant groups, alluding to the fact that we need to look beyond whether they are African American or Hispanic, and look at acculturation” (Int J MS Care. 2017;19[3]:131-9).
Then there’s the issue of Food and Drug Administration-approved disease-modifying therapies in MS and minorities. In an exploratory post hoc analysis of the Evidence of Interferon Dose-Response: European North American Comparative Efficacy (EVIDENCE) study, researchers found that African-American subjects experienced more exacerbations and were less likely to remain exacerbation free, compared with whites (Arch Neurol. 2005;62[11]:1681-3). The African-American subjects also developed more new MS lesions on T2-weighted brain MRI at 48 weeks (P = .04).
“There are a lot of unanswered questions, but understanding the effect of race/ethnicity is crucial to understanding MS disparities,” Dr. Amezcua said. “To better understand genetic variation in the context of health disparities, using ‘genetic ancestry’ could help with precision medicine. We must remember that minorities with MS face barriers related to access and education in MS care much more so than whites.”
She concluded her remarks by underscoring the importance of increasing minority participation in research and clinical trials. “But today, clinical trial participation by minorities is less than 10%. As we progress, and as we get closer to precision medicine, the health disparities will widen.”
She reported having no financial disclosures.
DALLAS – The way Lilyana Amezcua, MD, sees it, researchers should look beyond using race and ethnicity only as demographic variables when reporting results from multiple sclerosis studies.
“As a demographic variable we see it all the time: white versus non-white, and the methods to arrive at a category are seldom discussed,” Dr. Amezcua said at a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis. “We need to think about ethnocentric research, where the method for determination for race and ethnicity becomes important. This includes examining self-identity (ethnicity), along with physical characteristics and medical records, and confirming that beyond the individual.”
The goal, she continued, is to identify who is at risk for inferior health, such as trying to sort out biological and genetic explanations from non-biological explanations. Ethnocentric research also helps to address health care disparities. “But there’s a broad intersection between race and ethnicity, and depending on the question, genetic ancestry could help,” said Dr. Amezcua, a neurologist at the Keck School of Medicine at the University of Southern California, Los Angeles. “Race tries to infer biological differences, ethnicity infers societal differences, and ancestry infers genetic variations.”
While genetic and biologic features are often used to evaluate how race and ethnicity affects those with MS, Dr. Amezcua noted that several additional factors could influence outcomes. These include access to care as well as individual and community factors that relate to social determinants of health, such as poverty, exposures, and environmental stress. “These could be contributing to worse outcomes,” she said. “So could modifiable factors such as illness beliefs, health literacy, illness management, and acculturation.”
In terms of health literacy, there are reports suggesting that there is a general lack of adequate education and understanding about MS treatment and realistic expectations in African Americans and Hispanics, she said.
In addition, research has shown there is a lower probability of being under the care of a neurologist if you lack health insurance (odds ratio = 0.38) or are African American (OR = 0.52) or Hispanic (OR = 0.61), based on nationally representative data from the 2006-2013 Medical Expenditure Panel Survey (Neurology. 2017;88[24]:2268-75). “Just being African American or Hispanic lowered the probability of seeing a neurologist,” she said.
Published evidence also exists to suggest that illness beliefs drive some people away from MS treatment. “These are beliefs embedded in social and cultural factors known as cultural idioms,” Dr. Amezcua explained. “In a study that was able to capture qualitative and quantitative data, researchers found that social and cultural factors were more frequently reported in immigrant groups, alluding to the fact that we need to look beyond whether they are African American or Hispanic, and look at acculturation” (Int J MS Care. 2017;19[3]:131-9).
Then there’s the issue of Food and Drug Administration-approved disease-modifying therapies in MS and minorities. In an exploratory post hoc analysis of the Evidence of Interferon Dose-Response: European North American Comparative Efficacy (EVIDENCE) study, researchers found that African-American subjects experienced more exacerbations and were less likely to remain exacerbation free, compared with whites (Arch Neurol. 2005;62[11]:1681-3). The African-American subjects also developed more new MS lesions on T2-weighted brain MRI at 48 weeks (P = .04).
“There are a lot of unanswered questions, but understanding the effect of race/ethnicity is crucial to understanding MS disparities,” Dr. Amezcua said. “To better understand genetic variation in the context of health disparities, using ‘genetic ancestry’ could help with precision medicine. We must remember that minorities with MS face barriers related to access and education in MS care much more so than whites.”
She concluded her remarks by underscoring the importance of increasing minority participation in research and clinical trials. “But today, clinical trial participation by minorities is less than 10%. As we progress, and as we get closer to precision medicine, the health disparities will widen.”
She reported having no financial disclosures.
DALLAS – The way Lilyana Amezcua, MD, sees it, researchers should look beyond using race and ethnicity only as demographic variables when reporting results from multiple sclerosis studies.
“As a demographic variable we see it all the time: white versus non-white, and the methods to arrive at a category are seldom discussed,” Dr. Amezcua said at a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis. “We need to think about ethnocentric research, where the method for determination for race and ethnicity becomes important. This includes examining self-identity (ethnicity), along with physical characteristics and medical records, and confirming that beyond the individual.”
The goal, she continued, is to identify who is at risk for inferior health, such as trying to sort out biological and genetic explanations from non-biological explanations. Ethnocentric research also helps to address health care disparities. “But there’s a broad intersection between race and ethnicity, and depending on the question, genetic ancestry could help,” said Dr. Amezcua, a neurologist at the Keck School of Medicine at the University of Southern California, Los Angeles. “Race tries to infer biological differences, ethnicity infers societal differences, and ancestry infers genetic variations.”
While genetic and biologic features are often used to evaluate how race and ethnicity affects those with MS, Dr. Amezcua noted that several additional factors could influence outcomes. These include access to care as well as individual and community factors that relate to social determinants of health, such as poverty, exposures, and environmental stress. “These could be contributing to worse outcomes,” she said. “So could modifiable factors such as illness beliefs, health literacy, illness management, and acculturation.”
In terms of health literacy, there are reports suggesting that there is a general lack of adequate education and understanding about MS treatment and realistic expectations in African Americans and Hispanics, she said.
In addition, research has shown there is a lower probability of being under the care of a neurologist if you lack health insurance (odds ratio = 0.38) or are African American (OR = 0.52) or Hispanic (OR = 0.61), based on nationally representative data from the 2006-2013 Medical Expenditure Panel Survey (Neurology. 2017;88[24]:2268-75). “Just being African American or Hispanic lowered the probability of seeing a neurologist,” she said.
Published evidence also exists to suggest that illness beliefs drive some people away from MS treatment. “These are beliefs embedded in social and cultural factors known as cultural idioms,” Dr. Amezcua explained. “In a study that was able to capture qualitative and quantitative data, researchers found that social and cultural factors were more frequently reported in immigrant groups, alluding to the fact that we need to look beyond whether they are African American or Hispanic, and look at acculturation” (Int J MS Care. 2017;19[3]:131-9).
Then there’s the issue of Food and Drug Administration-approved disease-modifying therapies in MS and minorities. In an exploratory post hoc analysis of the Evidence of Interferon Dose-Response: European North American Comparative Efficacy (EVIDENCE) study, researchers found that African-American subjects experienced more exacerbations and were less likely to remain exacerbation free, compared with whites (Arch Neurol. 2005;62[11]:1681-3). The African-American subjects also developed more new MS lesions on T2-weighted brain MRI at 48 weeks (P = .04).
“There are a lot of unanswered questions, but understanding the effect of race/ethnicity is crucial to understanding MS disparities,” Dr. Amezcua said. “To better understand genetic variation in the context of health disparities, using ‘genetic ancestry’ could help with precision medicine. We must remember that minorities with MS face barriers related to access and education in MS care much more so than whites.”
She concluded her remarks by underscoring the importance of increasing minority participation in research and clinical trials. “But today, clinical trial participation by minorities is less than 10%. As we progress, and as we get closer to precision medicine, the health disparities will widen.”
She reported having no financial disclosures.
EXPERT ANALYSIS FROM ACTRIMS FORUM 2019
Smartphone technology helps to detect, track eye changes in MS
DALLAS – A battery of smartphone tests have been developed to help clinicians detect and monitor eye changes in MS patients.
At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, Randy H. Kardon, MD, PhD, said that there are two main high priority gaps to fill when it comes to better understanding the effects of MS on vision. “One, I think we need a way for early detection of visual pathway disturbances after either an acute clinical event or a subclinical event,” said Dr. Kardon, professor of neuro-ophthalmology at the University of Iowa, Iowa City. “Two, we need to monitor changes in the visual pathway over time in MS patients and capture variations due to changes in nerve conduction. The idea is, can we have a suite of smartphone tests that you can use in the clinic, but the patient can also use at home unsupervised, to get a time domain, so if there are fluctuations of core body temperature due to myelination, or subclinical changes going on, could we detect it earlier and monitor these patients? That’s the motivation.”
Although use of smartphone technology and mobile devices are emerging in health care settings, most of this technology is used sparingly in vision testing, mostly due to a lack of rigorous calibration of instruments and validation, said Dr. Kardon, who also directs the Iowa City VA Center for Prevention and Treatment of Visual Loss. To make a visual smartphone test viable, he continued, the visual output of the device must match the intended input in terms of multiple parameters (technical validation). Important parameters for vision tests include brightness, luminance, spatial resolution, and temporal resolution. Confounding variables include ambient lighting and viewing distance.
In his work with researchers from Aalborg University in Denmark, Dr. Kardon has developed four smartphone visual tests intended to be intuitive for patients. “We didn’t want something that was going to take more than 15 seconds,” he said. The visual tests include:
1. Critical flicker fusion, a test of optic nerve conduction. “This tests how well you can see a light flickering at a given temporal frequency at different levels of contrast, or how fast it can flicker before you don’t see a flicker anymore,” Dr. Kardon said. “The user sees spots that are flickering and just touches the ones they perceive to be flickering; they eliminate them by touching them.” When the test ends, the software “brackets what they did to a finer scale, and it finds the contrast at which that flicker wasn’t perceived anymore.”
2. The Landolt C visual acuity test. For this, the user must indicate the direction of the gap in the ring in a forced-choice task. “The user touches which arrow on the screen is pointing to where the location of the break in the Landolt C is perceived,” Dr. Kardon said. The Landolt C becomes progressively smaller until the location of the break can no longer be seen. “It’s pretty simple, and it finds the smallest size of the ‘C’ at which you’re making mistakes about 50% of the time, which is the threshold value for visual acuity,” he said.
3. Contrast sensitivity test at a fixed spatial frequency. “In this test, we fix the size of the letter to a large size, so spatial frequency is not at play, and we vary the contrast,” he said. “Users push the arrow wherever they see the break.” The contrast between the “C” and the background is sequentially reduced until a threshold is determined for the lowest contrast at which the location of the break in the “C” can still be observed.
4. Contrast sensitivity test at different spatial frequencies. This measure, also known as a vanishing optotype, is a line drawing of an object on a smooth, diffuse grayscale background. By altering the line properties used to define the shape of the vanishing optotype, one can vary its spatial frequency and contrast independent of target size. “This makes it an easy test because what the patient is asked to do is to touch wherever they see an object on the screen to eliminate it from the series of optotypes on the screen,” Dr. Kardon said. “The test is very fast, very intuitive.”
The researchers piloted use of these tests in a study of 104 age-matched control subjects and 117 MS patients. Of the 117 MS patients, 74 had a history of optic neuritis and 43 did not. The four tests were used in conjunction with standardized assessments, including the near-contrast acuity card test at 2.5%, the distant Early Treatment Diabetic Retinopathy Study (ETDRS) acuity test, as well as optical coherence tomography (OCT) of the retinal nerve fiber layer and ganglion cell layer thickness. Dr. Kardon and his colleagues found that when clinicians used a large target and varied the contrast, the test “did very well at differentiating normal from eyes with either previous optic neuritis or no previous optic neuritis,” he said. “It also differentiated eyes with previous optic neuritis and those with no optic neuritis. The visual acuity test didn’t perform as well because this is a near test. What we discovered afterward is that even at a fixed distance, many people who are presbyopic, or don’t have their optimal near correction, don’t do so well, because you’re testing spatial acuity. That’s a warning sign for future tests. You have to be careful as to how these are interpreted if they don’t have their best correction at near.”
Results from the critical flicker fusions tests were significant, except that they didn’t differentiate eyes affected by optic neuritis from those that weren’t. “The reason is that conduction was down in all of those eyes, so the combination of using contrast sensitivity and flicker fusion may not only help you diagnose MS, but whether that eye had been involved with optic neuritis before,” Dr. Kardon said. To date, he and his colleagues have completed technical validation of temporal frequency and contrast parameters. They’ve also completed preliminary investigations for determining test-retest variability, blurring effects, binocular summation effects, and quantification of normative ranges and abnormal subject data.
“A benefit of smartphone testing in MS is that visual dysfunction can be detected, leading to earlier interventions,” Dr. Kardon concluded. “We can study this on a time scale that wasn’t previously available. Wouldn’t you like to know on a daily or even a weekly basis what the fluctuations are in a home environment for MS patients? It’s low-cost, large-scale, and enables you to study genotype-phenotype comparisons.”
Going forward, Dr. Kardon and his colleagues have developed video cameras that go around the periphery of the iPad that can assess pupil and ocular motility, as well as eyelid and facial features in real time. He disclosed that he has received funding from the National Eye Institute, the Department of Defense, and from VA Rehabilitation Research and Development. He was also a member of the Novartis steering committee for the OCTiMS study and is a cofounder of MedFace and FaceX.
DALLAS – A battery of smartphone tests have been developed to help clinicians detect and monitor eye changes in MS patients.
At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, Randy H. Kardon, MD, PhD, said that there are two main high priority gaps to fill when it comes to better understanding the effects of MS on vision. “One, I think we need a way for early detection of visual pathway disturbances after either an acute clinical event or a subclinical event,” said Dr. Kardon, professor of neuro-ophthalmology at the University of Iowa, Iowa City. “Two, we need to monitor changes in the visual pathway over time in MS patients and capture variations due to changes in nerve conduction. The idea is, can we have a suite of smartphone tests that you can use in the clinic, but the patient can also use at home unsupervised, to get a time domain, so if there are fluctuations of core body temperature due to myelination, or subclinical changes going on, could we detect it earlier and monitor these patients? That’s the motivation.”
Although use of smartphone technology and mobile devices are emerging in health care settings, most of this technology is used sparingly in vision testing, mostly due to a lack of rigorous calibration of instruments and validation, said Dr. Kardon, who also directs the Iowa City VA Center for Prevention and Treatment of Visual Loss. To make a visual smartphone test viable, he continued, the visual output of the device must match the intended input in terms of multiple parameters (technical validation). Important parameters for vision tests include brightness, luminance, spatial resolution, and temporal resolution. Confounding variables include ambient lighting and viewing distance.
In his work with researchers from Aalborg University in Denmark, Dr. Kardon has developed four smartphone visual tests intended to be intuitive for patients. “We didn’t want something that was going to take more than 15 seconds,” he said. The visual tests include:
1. Critical flicker fusion, a test of optic nerve conduction. “This tests how well you can see a light flickering at a given temporal frequency at different levels of contrast, or how fast it can flicker before you don’t see a flicker anymore,” Dr. Kardon said. “The user sees spots that are flickering and just touches the ones they perceive to be flickering; they eliminate them by touching them.” When the test ends, the software “brackets what they did to a finer scale, and it finds the contrast at which that flicker wasn’t perceived anymore.”
2. The Landolt C visual acuity test. For this, the user must indicate the direction of the gap in the ring in a forced-choice task. “The user touches which arrow on the screen is pointing to where the location of the break in the Landolt C is perceived,” Dr. Kardon said. The Landolt C becomes progressively smaller until the location of the break can no longer be seen. “It’s pretty simple, and it finds the smallest size of the ‘C’ at which you’re making mistakes about 50% of the time, which is the threshold value for visual acuity,” he said.
3. Contrast sensitivity test at a fixed spatial frequency. “In this test, we fix the size of the letter to a large size, so spatial frequency is not at play, and we vary the contrast,” he said. “Users push the arrow wherever they see the break.” The contrast between the “C” and the background is sequentially reduced until a threshold is determined for the lowest contrast at which the location of the break in the “C” can still be observed.
4. Contrast sensitivity test at different spatial frequencies. This measure, also known as a vanishing optotype, is a line drawing of an object on a smooth, diffuse grayscale background. By altering the line properties used to define the shape of the vanishing optotype, one can vary its spatial frequency and contrast independent of target size. “This makes it an easy test because what the patient is asked to do is to touch wherever they see an object on the screen to eliminate it from the series of optotypes on the screen,” Dr. Kardon said. “The test is very fast, very intuitive.”
The researchers piloted use of these tests in a study of 104 age-matched control subjects and 117 MS patients. Of the 117 MS patients, 74 had a history of optic neuritis and 43 did not. The four tests were used in conjunction with standardized assessments, including the near-contrast acuity card test at 2.5%, the distant Early Treatment Diabetic Retinopathy Study (ETDRS) acuity test, as well as optical coherence tomography (OCT) of the retinal nerve fiber layer and ganglion cell layer thickness. Dr. Kardon and his colleagues found that when clinicians used a large target and varied the contrast, the test “did very well at differentiating normal from eyes with either previous optic neuritis or no previous optic neuritis,” he said. “It also differentiated eyes with previous optic neuritis and those with no optic neuritis. The visual acuity test didn’t perform as well because this is a near test. What we discovered afterward is that even at a fixed distance, many people who are presbyopic, or don’t have their optimal near correction, don’t do so well, because you’re testing spatial acuity. That’s a warning sign for future tests. You have to be careful as to how these are interpreted if they don’t have their best correction at near.”
Results from the critical flicker fusions tests were significant, except that they didn’t differentiate eyes affected by optic neuritis from those that weren’t. “The reason is that conduction was down in all of those eyes, so the combination of using contrast sensitivity and flicker fusion may not only help you diagnose MS, but whether that eye had been involved with optic neuritis before,” Dr. Kardon said. To date, he and his colleagues have completed technical validation of temporal frequency and contrast parameters. They’ve also completed preliminary investigations for determining test-retest variability, blurring effects, binocular summation effects, and quantification of normative ranges and abnormal subject data.
“A benefit of smartphone testing in MS is that visual dysfunction can be detected, leading to earlier interventions,” Dr. Kardon concluded. “We can study this on a time scale that wasn’t previously available. Wouldn’t you like to know on a daily or even a weekly basis what the fluctuations are in a home environment for MS patients? It’s low-cost, large-scale, and enables you to study genotype-phenotype comparisons.”
Going forward, Dr. Kardon and his colleagues have developed video cameras that go around the periphery of the iPad that can assess pupil and ocular motility, as well as eyelid and facial features in real time. He disclosed that he has received funding from the National Eye Institute, the Department of Defense, and from VA Rehabilitation Research and Development. He was also a member of the Novartis steering committee for the OCTiMS study and is a cofounder of MedFace and FaceX.
DALLAS – A battery of smartphone tests have been developed to help clinicians detect and monitor eye changes in MS patients.
At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, Randy H. Kardon, MD, PhD, said that there are two main high priority gaps to fill when it comes to better understanding the effects of MS on vision. “One, I think we need a way for early detection of visual pathway disturbances after either an acute clinical event or a subclinical event,” said Dr. Kardon, professor of neuro-ophthalmology at the University of Iowa, Iowa City. “Two, we need to monitor changes in the visual pathway over time in MS patients and capture variations due to changes in nerve conduction. The idea is, can we have a suite of smartphone tests that you can use in the clinic, but the patient can also use at home unsupervised, to get a time domain, so if there are fluctuations of core body temperature due to myelination, or subclinical changes going on, could we detect it earlier and monitor these patients? That’s the motivation.”
Although use of smartphone technology and mobile devices are emerging in health care settings, most of this technology is used sparingly in vision testing, mostly due to a lack of rigorous calibration of instruments and validation, said Dr. Kardon, who also directs the Iowa City VA Center for Prevention and Treatment of Visual Loss. To make a visual smartphone test viable, he continued, the visual output of the device must match the intended input in terms of multiple parameters (technical validation). Important parameters for vision tests include brightness, luminance, spatial resolution, and temporal resolution. Confounding variables include ambient lighting and viewing distance.
In his work with researchers from Aalborg University in Denmark, Dr. Kardon has developed four smartphone visual tests intended to be intuitive for patients. “We didn’t want something that was going to take more than 15 seconds,” he said. The visual tests include:
1. Critical flicker fusion, a test of optic nerve conduction. “This tests how well you can see a light flickering at a given temporal frequency at different levels of contrast, or how fast it can flicker before you don’t see a flicker anymore,” Dr. Kardon said. “The user sees spots that are flickering and just touches the ones they perceive to be flickering; they eliminate them by touching them.” When the test ends, the software “brackets what they did to a finer scale, and it finds the contrast at which that flicker wasn’t perceived anymore.”
2. The Landolt C visual acuity test. For this, the user must indicate the direction of the gap in the ring in a forced-choice task. “The user touches which arrow on the screen is pointing to where the location of the break in the Landolt C is perceived,” Dr. Kardon said. The Landolt C becomes progressively smaller until the location of the break can no longer be seen. “It’s pretty simple, and it finds the smallest size of the ‘C’ at which you’re making mistakes about 50% of the time, which is the threshold value for visual acuity,” he said.
3. Contrast sensitivity test at a fixed spatial frequency. “In this test, we fix the size of the letter to a large size, so spatial frequency is not at play, and we vary the contrast,” he said. “Users push the arrow wherever they see the break.” The contrast between the “C” and the background is sequentially reduced until a threshold is determined for the lowest contrast at which the location of the break in the “C” can still be observed.
4. Contrast sensitivity test at different spatial frequencies. This measure, also known as a vanishing optotype, is a line drawing of an object on a smooth, diffuse grayscale background. By altering the line properties used to define the shape of the vanishing optotype, one can vary its spatial frequency and contrast independent of target size. “This makes it an easy test because what the patient is asked to do is to touch wherever they see an object on the screen to eliminate it from the series of optotypes on the screen,” Dr. Kardon said. “The test is very fast, very intuitive.”
The researchers piloted use of these tests in a study of 104 age-matched control subjects and 117 MS patients. Of the 117 MS patients, 74 had a history of optic neuritis and 43 did not. The four tests were used in conjunction with standardized assessments, including the near-contrast acuity card test at 2.5%, the distant Early Treatment Diabetic Retinopathy Study (ETDRS) acuity test, as well as optical coherence tomography (OCT) of the retinal nerve fiber layer and ganglion cell layer thickness. Dr. Kardon and his colleagues found that when clinicians used a large target and varied the contrast, the test “did very well at differentiating normal from eyes with either previous optic neuritis or no previous optic neuritis,” he said. “It also differentiated eyes with previous optic neuritis and those with no optic neuritis. The visual acuity test didn’t perform as well because this is a near test. What we discovered afterward is that even at a fixed distance, many people who are presbyopic, or don’t have their optimal near correction, don’t do so well, because you’re testing spatial acuity. That’s a warning sign for future tests. You have to be careful as to how these are interpreted if they don’t have their best correction at near.”
Results from the critical flicker fusions tests were significant, except that they didn’t differentiate eyes affected by optic neuritis from those that weren’t. “The reason is that conduction was down in all of those eyes, so the combination of using contrast sensitivity and flicker fusion may not only help you diagnose MS, but whether that eye had been involved with optic neuritis before,” Dr. Kardon said. To date, he and his colleagues have completed technical validation of temporal frequency and contrast parameters. They’ve also completed preliminary investigations for determining test-retest variability, blurring effects, binocular summation effects, and quantification of normative ranges and abnormal subject data.
“A benefit of smartphone testing in MS is that visual dysfunction can be detected, leading to earlier interventions,” Dr. Kardon concluded. “We can study this on a time scale that wasn’t previously available. Wouldn’t you like to know on a daily or even a weekly basis what the fluctuations are in a home environment for MS patients? It’s low-cost, large-scale, and enables you to study genotype-phenotype comparisons.”
Going forward, Dr. Kardon and his colleagues have developed video cameras that go around the periphery of the iPad that can assess pupil and ocular motility, as well as eyelid and facial features in real time. He disclosed that he has received funding from the National Eye Institute, the Department of Defense, and from VA Rehabilitation Research and Development. He was also a member of the Novartis steering committee for the OCTiMS study and is a cofounder of MedFace and FaceX.
EXPERT ANALYSIS FROM ACTRIMS FORUM 2019
Study eyes serious adverse events from long-term rituximab use in MS
DALLAS – An analysis of two large cohorts treated with rituximab (Rituxan) showed that the rate of serious infections was 8.1%, yet no life-threatening infusion reactions occurred.
The finding comes from a retrospective chart review of 500 patients treated at the Rocky Mountain Multiple Sclerosis Center at the University of Colorado at Denver, Aurora, and 269 treated at the New York University Multiple Sclerosis Comprehensive Care Center.
At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, one of the study authors, Brandi L. Vollmer, MPH, noted that while rituximab is used off-label to treat multiple sclerosis (MS) and related disorders, limited long-term data for MS patients exist. Ms. Vollmer, a professional research assistant in the department of neurology in the division of neuroimmunology at the University of Colorado at Denver, and her associates identified all patients at the two MS centers who received at least one dose of rituximab. They reviewed patient charts from rituximab start date until 12 months after the last rituximab end date, or last ocrelizumab (Ocrevus) infusion in cases where patients switched to ocrelizumab without interruption with any other disease-modifying therapy. Data were abstracted from each chart using a case report form that systematically queried for demographic and clinical characteristics, serious adverse events, and significant laboratory abnormalities. The researchers used descriptive statistics to describe the sample group.
Key outcomes of interest were infusion reactions that were life-threatening or resulted in a hospitalization; infections that resulted in hospitalization, the need for IV antibiotics, or extended antibiotics; abnormal lab values; new diagnosis of malignant cancer; new diagnosis of autoimmune disease; diagnosis of serious thromboembolism; and mortality within 12 months of last infusion. At baseline, the mean age of the 769 patients was 43 years, 69% were female, 64% were white, and 16% were black. More than half (58%) had a diagnosis of relapsing-remitting MS, followed by secondary progressive MS (20%), primary progressive MS (11%), neuromyelitis optica spectrum disorder (9%), or other, and their mean disease duration was 8 years.
The researchers reported that the mean cumulative rituximab dose was 4,124 mg (median of 3,000 mg), the mean dose of ocrelizumab for ocrelizumab-switchers was 1,087 mg, and the mean time of follow-up was 33 months. Infections while on rituximab/ocrelizumab resulting in a hospitalization were observed in 50 patients (6.5%), which were primarily urinary tract infections (UTIs; 19 cases), pneumonia (12 cases), and sepsis (12 cases), while 7 patients (0.9%) experienced an infection that resulted in extended dosing antibiotics, including 5 recurrent UTIs, 1 case of bacteremia, and 1 case of osteomyelitis.
Ms. Vollmer and her colleagues also found that five patients (0.7%) experienced an infection that resulted in IV antibiotics without hospitalization, including one case each of pneumonia, cellulitis, UTI, infected wound, and aspiration pneumonia with respiratory syncytial virus. Serious de novo diagnoses while on rituximab were reported for 18 patients (2%), including autoimmune disease in 4, non-skin neoplasm in 7, and serious thromboembolic events in 7.
No patient experienced an infusion reaction requiring hospitalization. However, one patient received epinephrine after seeking care at an emergency department post infusion. Twelve patients (2%) died within 12 months of their last rituximab dose, although none were deemed by the treating clinician to be related to rituximab. Significant neutropenia was observed in 12 (2%), lymphopenia in 46 (6%), and IgG values below 500 mg/dL in 28 (4%).
“So far, this is just a descriptive analysis,” Ms. Vollmer said. “We want to look further into how abnormal lab values correlate with serious infections in particular.”
She acknowledged certain limitations of the study, including its retrospective design. Ms. Vollmer reported having no financial disclosures. Many of her coauthors reporting having numerous financial ties to the pharmaceutical industry.
SOURCE: Vollmer B et al. ACTRIMS Forum 2019, Poster 113
DALLAS – An analysis of two large cohorts treated with rituximab (Rituxan) showed that the rate of serious infections was 8.1%, yet no life-threatening infusion reactions occurred.
The finding comes from a retrospective chart review of 500 patients treated at the Rocky Mountain Multiple Sclerosis Center at the University of Colorado at Denver, Aurora, and 269 treated at the New York University Multiple Sclerosis Comprehensive Care Center.
At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, one of the study authors, Brandi L. Vollmer, MPH, noted that while rituximab is used off-label to treat multiple sclerosis (MS) and related disorders, limited long-term data for MS patients exist. Ms. Vollmer, a professional research assistant in the department of neurology in the division of neuroimmunology at the University of Colorado at Denver, and her associates identified all patients at the two MS centers who received at least one dose of rituximab. They reviewed patient charts from rituximab start date until 12 months after the last rituximab end date, or last ocrelizumab (Ocrevus) infusion in cases where patients switched to ocrelizumab without interruption with any other disease-modifying therapy. Data were abstracted from each chart using a case report form that systematically queried for demographic and clinical characteristics, serious adverse events, and significant laboratory abnormalities. The researchers used descriptive statistics to describe the sample group.
Key outcomes of interest were infusion reactions that were life-threatening or resulted in a hospitalization; infections that resulted in hospitalization, the need for IV antibiotics, or extended antibiotics; abnormal lab values; new diagnosis of malignant cancer; new diagnosis of autoimmune disease; diagnosis of serious thromboembolism; and mortality within 12 months of last infusion. At baseline, the mean age of the 769 patients was 43 years, 69% were female, 64% were white, and 16% were black. More than half (58%) had a diagnosis of relapsing-remitting MS, followed by secondary progressive MS (20%), primary progressive MS (11%), neuromyelitis optica spectrum disorder (9%), or other, and their mean disease duration was 8 years.
The researchers reported that the mean cumulative rituximab dose was 4,124 mg (median of 3,000 mg), the mean dose of ocrelizumab for ocrelizumab-switchers was 1,087 mg, and the mean time of follow-up was 33 months. Infections while on rituximab/ocrelizumab resulting in a hospitalization were observed in 50 patients (6.5%), which were primarily urinary tract infections (UTIs; 19 cases), pneumonia (12 cases), and sepsis (12 cases), while 7 patients (0.9%) experienced an infection that resulted in extended dosing antibiotics, including 5 recurrent UTIs, 1 case of bacteremia, and 1 case of osteomyelitis.
Ms. Vollmer and her colleagues also found that five patients (0.7%) experienced an infection that resulted in IV antibiotics without hospitalization, including one case each of pneumonia, cellulitis, UTI, infected wound, and aspiration pneumonia with respiratory syncytial virus. Serious de novo diagnoses while on rituximab were reported for 18 patients (2%), including autoimmune disease in 4, non-skin neoplasm in 7, and serious thromboembolic events in 7.
No patient experienced an infusion reaction requiring hospitalization. However, one patient received epinephrine after seeking care at an emergency department post infusion. Twelve patients (2%) died within 12 months of their last rituximab dose, although none were deemed by the treating clinician to be related to rituximab. Significant neutropenia was observed in 12 (2%), lymphopenia in 46 (6%), and IgG values below 500 mg/dL in 28 (4%).
“So far, this is just a descriptive analysis,” Ms. Vollmer said. “We want to look further into how abnormal lab values correlate with serious infections in particular.”
She acknowledged certain limitations of the study, including its retrospective design. Ms. Vollmer reported having no financial disclosures. Many of her coauthors reporting having numerous financial ties to the pharmaceutical industry.
SOURCE: Vollmer B et al. ACTRIMS Forum 2019, Poster 113
DALLAS – An analysis of two large cohorts treated with rituximab (Rituxan) showed that the rate of serious infections was 8.1%, yet no life-threatening infusion reactions occurred.
The finding comes from a retrospective chart review of 500 patients treated at the Rocky Mountain Multiple Sclerosis Center at the University of Colorado at Denver, Aurora, and 269 treated at the New York University Multiple Sclerosis Comprehensive Care Center.
At a meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis, one of the study authors, Brandi L. Vollmer, MPH, noted that while rituximab is used off-label to treat multiple sclerosis (MS) and related disorders, limited long-term data for MS patients exist. Ms. Vollmer, a professional research assistant in the department of neurology in the division of neuroimmunology at the University of Colorado at Denver, and her associates identified all patients at the two MS centers who received at least one dose of rituximab. They reviewed patient charts from rituximab start date until 12 months after the last rituximab end date, or last ocrelizumab (Ocrevus) infusion in cases where patients switched to ocrelizumab without interruption with any other disease-modifying therapy. Data were abstracted from each chart using a case report form that systematically queried for demographic and clinical characteristics, serious adverse events, and significant laboratory abnormalities. The researchers used descriptive statistics to describe the sample group.
Key outcomes of interest were infusion reactions that were life-threatening or resulted in a hospitalization; infections that resulted in hospitalization, the need for IV antibiotics, or extended antibiotics; abnormal lab values; new diagnosis of malignant cancer; new diagnosis of autoimmune disease; diagnosis of serious thromboembolism; and mortality within 12 months of last infusion. At baseline, the mean age of the 769 patients was 43 years, 69% were female, 64% were white, and 16% were black. More than half (58%) had a diagnosis of relapsing-remitting MS, followed by secondary progressive MS (20%), primary progressive MS (11%), neuromyelitis optica spectrum disorder (9%), or other, and their mean disease duration was 8 years.
The researchers reported that the mean cumulative rituximab dose was 4,124 mg (median of 3,000 mg), the mean dose of ocrelizumab for ocrelizumab-switchers was 1,087 mg, and the mean time of follow-up was 33 months. Infections while on rituximab/ocrelizumab resulting in a hospitalization were observed in 50 patients (6.5%), which were primarily urinary tract infections (UTIs; 19 cases), pneumonia (12 cases), and sepsis (12 cases), while 7 patients (0.9%) experienced an infection that resulted in extended dosing antibiotics, including 5 recurrent UTIs, 1 case of bacteremia, and 1 case of osteomyelitis.
Ms. Vollmer and her colleagues also found that five patients (0.7%) experienced an infection that resulted in IV antibiotics without hospitalization, including one case each of pneumonia, cellulitis, UTI, infected wound, and aspiration pneumonia with respiratory syncytial virus. Serious de novo diagnoses while on rituximab were reported for 18 patients (2%), including autoimmune disease in 4, non-skin neoplasm in 7, and serious thromboembolic events in 7.
No patient experienced an infusion reaction requiring hospitalization. However, one patient received epinephrine after seeking care at an emergency department post infusion. Twelve patients (2%) died within 12 months of their last rituximab dose, although none were deemed by the treating clinician to be related to rituximab. Significant neutropenia was observed in 12 (2%), lymphopenia in 46 (6%), and IgG values below 500 mg/dL in 28 (4%).
“So far, this is just a descriptive analysis,” Ms. Vollmer said. “We want to look further into how abnormal lab values correlate with serious infections in particular.”
She acknowledged certain limitations of the study, including its retrospective design. Ms. Vollmer reported having no financial disclosures. Many of her coauthors reporting having numerous financial ties to the pharmaceutical industry.
SOURCE: Vollmer B et al. ACTRIMS Forum 2019, Poster 113
REPORTING FROM ACTRIMS 2019
NIH director updates study enrolling one million participants
NEW ORLEANS – It is not too late to enroll your patients or yourself into the largest longitudinal cohort study ever initiated, according to Francis S. Collins, MD, PhD, who is director of the National Institutes of Health (NIH).
Since May 2018, when it was initiated, the NIH-funded All of Us Research Program has already enrolled 200,000 of the planned goal of one million participants in the United States. Of these, approximately half have already provided baseline demographics and health information as well as their consent to use the slew of health data that is being collected.
“The only way to do this kind of thing is to have data – a lot of it,” said Dr. Collins, explaining the premise of the All of Us Research Program in an interview conducted at the annual meeting of the Endocrine Society.
The data are not limited to medical records: Blood samples, whole genome sequencing, wearable activity monitors, and subject-completed questionnaires are among a long list of sources of information to be collected from participants, who are expected to be followed indefinitely.
According to Dr. Collins, who delivered a plenary address at the meeting, these data will become more valuable over time, one of the most important goals of this study is to prepare the way for precision medicine. As opposed to the traditional one-size-fits-all approach to treating disease, he believes that this large dataset will allow researchers to understand differences in common diseases at the individual level.
In relation to endocrinology, Dr. Collins said that a cohort of one million participants would be expected to have close to 100,000 individuals with diabetes mellitus.
“This is going to be transformative,” said Dr. Collins, who emphasized that the enrollment is specifically designed to capture participants from diverse ethnic and racial groups.
All of the data collected will be made broadly available to research initiatives of all kinds, many of which have not yet even been envisioned.
Information on enrollment is available on line: joinallofus.org.
NEW ORLEANS – It is not too late to enroll your patients or yourself into the largest longitudinal cohort study ever initiated, according to Francis S. Collins, MD, PhD, who is director of the National Institutes of Health (NIH).
Since May 2018, when it was initiated, the NIH-funded All of Us Research Program has already enrolled 200,000 of the planned goal of one million participants in the United States. Of these, approximately half have already provided baseline demographics and health information as well as their consent to use the slew of health data that is being collected.
“The only way to do this kind of thing is to have data – a lot of it,” said Dr. Collins, explaining the premise of the All of Us Research Program in an interview conducted at the annual meeting of the Endocrine Society.
The data are not limited to medical records: Blood samples, whole genome sequencing, wearable activity monitors, and subject-completed questionnaires are among a long list of sources of information to be collected from participants, who are expected to be followed indefinitely.
According to Dr. Collins, who delivered a plenary address at the meeting, these data will become more valuable over time, one of the most important goals of this study is to prepare the way for precision medicine. As opposed to the traditional one-size-fits-all approach to treating disease, he believes that this large dataset will allow researchers to understand differences in common diseases at the individual level.
In relation to endocrinology, Dr. Collins said that a cohort of one million participants would be expected to have close to 100,000 individuals with diabetes mellitus.
“This is going to be transformative,” said Dr. Collins, who emphasized that the enrollment is specifically designed to capture participants from diverse ethnic and racial groups.
All of the data collected will be made broadly available to research initiatives of all kinds, many of which have not yet even been envisioned.
Information on enrollment is available on line: joinallofus.org.
NEW ORLEANS – It is not too late to enroll your patients or yourself into the largest longitudinal cohort study ever initiated, according to Francis S. Collins, MD, PhD, who is director of the National Institutes of Health (NIH).
Since May 2018, when it was initiated, the NIH-funded All of Us Research Program has already enrolled 200,000 of the planned goal of one million participants in the United States. Of these, approximately half have already provided baseline demographics and health information as well as their consent to use the slew of health data that is being collected.
“The only way to do this kind of thing is to have data – a lot of it,” said Dr. Collins, explaining the premise of the All of Us Research Program in an interview conducted at the annual meeting of the Endocrine Society.
The data are not limited to medical records: Blood samples, whole genome sequencing, wearable activity monitors, and subject-completed questionnaires are among a long list of sources of information to be collected from participants, who are expected to be followed indefinitely.
According to Dr. Collins, who delivered a plenary address at the meeting, these data will become more valuable over time, one of the most important goals of this study is to prepare the way for precision medicine. As opposed to the traditional one-size-fits-all approach to treating disease, he believes that this large dataset will allow researchers to understand differences in common diseases at the individual level.
In relation to endocrinology, Dr. Collins said that a cohort of one million participants would be expected to have close to 100,000 individuals with diabetes mellitus.
“This is going to be transformative,” said Dr. Collins, who emphasized that the enrollment is specifically designed to capture participants from diverse ethnic and racial groups.
All of the data collected will be made broadly available to research initiatives of all kinds, many of which have not yet even been envisioned.
Information on enrollment is available on line: joinallofus.org.
REPORTING FROM ENDO 2019
Syncope session showcases latest research and guidance for practice
Syncope is a common problem, but an area in which practice likely varies by region and provider, according to Carrie Herzke, MD, SFHM, of Johns Hopkins University in Baltimore.
The variation in practice also suggests opportunities to safely cut costs, Dr. Herzke said in an interview.
Dr. Herzke will review the recent literature and summarize the current guidelines related to the treatment of syncope in her session, “SyncopE – Effective, Efficient and Economic Evaluations,” on Monday, March 25, at HM19.
“At the end of this session I am hopeful attendees will have a better understanding of the current guidelines, as well as which tests are most likely to be high value in the evaluation of syncope,” Dr. Herzke said. But before testing, clinicians should keep in mind that a history and physical examination are key components to evaluating syncope, she noted.
The European Society of Cardiology Guidelines for Syncope, published in 2018, feature several new concepts for evaluating and managing syncope in clinical settings and testing, including tilt testing, a greater role for prolonged ECG monitoring, use of video recording for suspected syncope, consideration of adenosine sensitive syncope, and consideration of neurological causes of syncope.
The ESC guidelines include using algorithms to determine the appropriate therapy for reflex syncope based on age, severity, and clinical forms. The guidelines also address diagnostic tests, monitoring in and out of the hospital, and treatment options including lifestyle changes and education as well as pharmacotherapy.
Dr. Herzke also will review the 2017 ACC/AHA/HRS Guideline for Patients With Syncope, published in 2017 in the journal Circulation. This guideline has an algorithm for initial evaluation of patients with syncope that includes a history, physical, and ECG. If the cause is known, patients should be assessed for risk and treated; syncope of unknown cause requires further evaluation, and the guideline presents recommendations for additional assessment through means including cardiac imaging, stress testing, blood testing, neurological testing, and tilt table testing.
“The selection of a given diagnostic test, after the initial history, physical examination, and baseline ECG, is a clinical decision based on the patient’s clinical presentation, risk stratification, and a clear understanding of diagnostic and prognostic value of any further testing,” according to the guideline authors.
The 2017 ACC/AHA/HRS Guideline for Patients With Syncope also provides recommendations for the management of cardiovascular conditions, including arrhythmic and structural conditions.
Dr. Herzke said she thinks that the topic of pulmonary embolism and syncope may prompt the liveliest discussion, and she will include several recent articles on this topic in her literature review.
“There has been some debate about how often PE is present in patients presenting after a syncopal episode,” she said. A recent study published in JAMA Internal Medicine found a prevalence of PE from 0.06% to 0.55% among all adults presenting to an ED with syncope and a prevalence of PE from 0.14% to 0.83%.
SyncopE – Effective, Efficient and Economic Evaluations
Monday 1:10 pm
Maryland BD/4-6
Syncope is a common problem, but an area in which practice likely varies by region and provider, according to Carrie Herzke, MD, SFHM, of Johns Hopkins University in Baltimore.
The variation in practice also suggests opportunities to safely cut costs, Dr. Herzke said in an interview.
Dr. Herzke will review the recent literature and summarize the current guidelines related to the treatment of syncope in her session, “SyncopE – Effective, Efficient and Economic Evaluations,” on Monday, March 25, at HM19.
“At the end of this session I am hopeful attendees will have a better understanding of the current guidelines, as well as which tests are most likely to be high value in the evaluation of syncope,” Dr. Herzke said. But before testing, clinicians should keep in mind that a history and physical examination are key components to evaluating syncope, she noted.
The European Society of Cardiology Guidelines for Syncope, published in 2018, feature several new concepts for evaluating and managing syncope in clinical settings and testing, including tilt testing, a greater role for prolonged ECG monitoring, use of video recording for suspected syncope, consideration of adenosine sensitive syncope, and consideration of neurological causes of syncope.
The ESC guidelines include using algorithms to determine the appropriate therapy for reflex syncope based on age, severity, and clinical forms. The guidelines also address diagnostic tests, monitoring in and out of the hospital, and treatment options including lifestyle changes and education as well as pharmacotherapy.
Dr. Herzke also will review the 2017 ACC/AHA/HRS Guideline for Patients With Syncope, published in 2017 in the journal Circulation. This guideline has an algorithm for initial evaluation of patients with syncope that includes a history, physical, and ECG. If the cause is known, patients should be assessed for risk and treated; syncope of unknown cause requires further evaluation, and the guideline presents recommendations for additional assessment through means including cardiac imaging, stress testing, blood testing, neurological testing, and tilt table testing.
“The selection of a given diagnostic test, after the initial history, physical examination, and baseline ECG, is a clinical decision based on the patient’s clinical presentation, risk stratification, and a clear understanding of diagnostic and prognostic value of any further testing,” according to the guideline authors.
The 2017 ACC/AHA/HRS Guideline for Patients With Syncope also provides recommendations for the management of cardiovascular conditions, including arrhythmic and structural conditions.
Dr. Herzke said she thinks that the topic of pulmonary embolism and syncope may prompt the liveliest discussion, and she will include several recent articles on this topic in her literature review.
“There has been some debate about how often PE is present in patients presenting after a syncopal episode,” she said. A recent study published in JAMA Internal Medicine found a prevalence of PE from 0.06% to 0.55% among all adults presenting to an ED with syncope and a prevalence of PE from 0.14% to 0.83%.
SyncopE – Effective, Efficient and Economic Evaluations
Monday 1:10 pm
Maryland BD/4-6
Syncope is a common problem, but an area in which practice likely varies by region and provider, according to Carrie Herzke, MD, SFHM, of Johns Hopkins University in Baltimore.
The variation in practice also suggests opportunities to safely cut costs, Dr. Herzke said in an interview.
Dr. Herzke will review the recent literature and summarize the current guidelines related to the treatment of syncope in her session, “SyncopE – Effective, Efficient and Economic Evaluations,” on Monday, March 25, at HM19.
“At the end of this session I am hopeful attendees will have a better understanding of the current guidelines, as well as which tests are most likely to be high value in the evaluation of syncope,” Dr. Herzke said. But before testing, clinicians should keep in mind that a history and physical examination are key components to evaluating syncope, she noted.
The European Society of Cardiology Guidelines for Syncope, published in 2018, feature several new concepts for evaluating and managing syncope in clinical settings and testing, including tilt testing, a greater role for prolonged ECG monitoring, use of video recording for suspected syncope, consideration of adenosine sensitive syncope, and consideration of neurological causes of syncope.
The ESC guidelines include using algorithms to determine the appropriate therapy for reflex syncope based on age, severity, and clinical forms. The guidelines also address diagnostic tests, monitoring in and out of the hospital, and treatment options including lifestyle changes and education as well as pharmacotherapy.
Dr. Herzke also will review the 2017 ACC/AHA/HRS Guideline for Patients With Syncope, published in 2017 in the journal Circulation. This guideline has an algorithm for initial evaluation of patients with syncope that includes a history, physical, and ECG. If the cause is known, patients should be assessed for risk and treated; syncope of unknown cause requires further evaluation, and the guideline presents recommendations for additional assessment through means including cardiac imaging, stress testing, blood testing, neurological testing, and tilt table testing.
“The selection of a given diagnostic test, after the initial history, physical examination, and baseline ECG, is a clinical decision based on the patient’s clinical presentation, risk stratification, and a clear understanding of diagnostic and prognostic value of any further testing,” according to the guideline authors.
The 2017 ACC/AHA/HRS Guideline for Patients With Syncope also provides recommendations for the management of cardiovascular conditions, including arrhythmic and structural conditions.
Dr. Herzke said she thinks that the topic of pulmonary embolism and syncope may prompt the liveliest discussion, and she will include several recent articles on this topic in her literature review.
“There has been some debate about how often PE is present in patients presenting after a syncopal episode,” she said. A recent study published in JAMA Internal Medicine found a prevalence of PE from 0.06% to 0.55% among all adults presenting to an ED with syncope and a prevalence of PE from 0.14% to 0.83%.
SyncopE – Effective, Efficient and Economic Evaluations
Monday 1:10 pm
Maryland BD/4-6
Simple screening for risk of falling in elderly can guide prevention
NEW ORLEANS – , according to an update on this field at the annual meeting at the Endocrine Society.
“The risk of falling in older adults is very high, but risk can be evaluated, and there are effective strategies for risk reduction,” reported Kenton R. Kaufman, PhD, codirector of the Biomechanics and Motion Analysis Laboratory at the Mayo Clinic, Rochester, Minn.
There is not much debate that aging individuals are at an increased risk of falls, but Dr. Kaufman presented his own set of data to reinforce this point. In a longitudinal study of 125 individuals over the age of 65 years who were followed for a year at his institution, 59% had at least one fall even though all were healthy and functional when enrolled.
“It was more common to fall in summer than in winter, and most occurred on a level surface,” said Dr. Kaufman citing data from a study published 2 years ago (Arch Gerontol Geriatr. 2017;73:240-7). About half of the falls occurred at home.
Only 20%-30% of falls lead to moderate to severe injuries, but this is enough to make fall prevention an appropriate and important focus of public health initiatives to reduce morbidity and lower health costs, according to Dr. Kaufman, citing data suggesting that the medical costs total in the billions of dollars.
As a result of a substantial body of research in this area, there are now multiple clinical tests, such as grip strength, the functional reach test, and the 5-minute walk, that provide some degree of predictive value for identifying elderly individuals at risk for falls.
In addition, simple questionnaires that measure the fear of falling, such as the Activities-Specific Balance Confidence Scale (ABC test), and the Falls Efficacy Scale, also identify individuals at higher risk of falling. According to Dr. Kaufman, the predictive value of these questionnaires stems from the fact that those with more fears are more likely to fall.
Dr. Kaufman advised using these simple measures alone or in combination to screen aging patients for risk of failing. Although he singled out grip strength and the ABC test as the clinical test and the questionnaire he is most likely to employ, he believes others are also reasonable. When performed by primary care physicians, although not specialists, evaluating patients for risk of falling is Medicare-reimbursable, according to Dr. Kaufman.
There are two components to effective prophylaxis. One is improving muscle strength. The other is improving neuromuscular response, which means moving quickly enough to compensate when one’s center of gravity is disturbed. According to Dr. Kaufman, who cited two randomized trials, exercise to restore muscle strength can by itself reduce the risk of falling by 10%-20%.
Neuromuscular training is more intensive and not widely available but very effective. This involves training patients to improve their reaction time in the event of an impending fall. This approach, called postural perturbation training, employs a harness to prevent injury.
“The elderly can lose their facility for rapid recovery but this can be relearned,” said Dr. Kaufman, who cited another two randomized trials with this approach that reduced falls by 45% and 55%.
Postural perturbation training, although used to train amputees to gain comfort ambulating on artificial limbs, has so far had limited use in the elderly, but Dr. Kaufman said it might have utility in selected individuals, and he noted that there is at least one commercial device now being marketed.
Many elderly patients will not be candidates for training to reduce falls due to frailty or comorbid conditions that prevent exercise, but Dr. Kaufman encouraged clinicians to evaluate risk of falls in aging individuals who are active because there are strategies to reduce risk, and falls are a major source of morbidity and mortality.
Even for those who are not suitable for risk reduction strategies, testing for risk of falls has the ancillary benefit of raising awareness, according to Dr. Kaufman.
Dr. Kaufman reported no relevant financial relationships to disclose.
NEW ORLEANS – , according to an update on this field at the annual meeting at the Endocrine Society.
“The risk of falling in older adults is very high, but risk can be evaluated, and there are effective strategies for risk reduction,” reported Kenton R. Kaufman, PhD, codirector of the Biomechanics and Motion Analysis Laboratory at the Mayo Clinic, Rochester, Minn.
There is not much debate that aging individuals are at an increased risk of falls, but Dr. Kaufman presented his own set of data to reinforce this point. In a longitudinal study of 125 individuals over the age of 65 years who were followed for a year at his institution, 59% had at least one fall even though all were healthy and functional when enrolled.
“It was more common to fall in summer than in winter, and most occurred on a level surface,” said Dr. Kaufman citing data from a study published 2 years ago (Arch Gerontol Geriatr. 2017;73:240-7). About half of the falls occurred at home.
Only 20%-30% of falls lead to moderate to severe injuries, but this is enough to make fall prevention an appropriate and important focus of public health initiatives to reduce morbidity and lower health costs, according to Dr. Kaufman, citing data suggesting that the medical costs total in the billions of dollars.
As a result of a substantial body of research in this area, there are now multiple clinical tests, such as grip strength, the functional reach test, and the 5-minute walk, that provide some degree of predictive value for identifying elderly individuals at risk for falls.
In addition, simple questionnaires that measure the fear of falling, such as the Activities-Specific Balance Confidence Scale (ABC test), and the Falls Efficacy Scale, also identify individuals at higher risk of falling. According to Dr. Kaufman, the predictive value of these questionnaires stems from the fact that those with more fears are more likely to fall.
Dr. Kaufman advised using these simple measures alone or in combination to screen aging patients for risk of failing. Although he singled out grip strength and the ABC test as the clinical test and the questionnaire he is most likely to employ, he believes others are also reasonable. When performed by primary care physicians, although not specialists, evaluating patients for risk of falling is Medicare-reimbursable, according to Dr. Kaufman.
There are two components to effective prophylaxis. One is improving muscle strength. The other is improving neuromuscular response, which means moving quickly enough to compensate when one’s center of gravity is disturbed. According to Dr. Kaufman, who cited two randomized trials, exercise to restore muscle strength can by itself reduce the risk of falling by 10%-20%.
Neuromuscular training is more intensive and not widely available but very effective. This involves training patients to improve their reaction time in the event of an impending fall. This approach, called postural perturbation training, employs a harness to prevent injury.
“The elderly can lose their facility for rapid recovery but this can be relearned,” said Dr. Kaufman, who cited another two randomized trials with this approach that reduced falls by 45% and 55%.
Postural perturbation training, although used to train amputees to gain comfort ambulating on artificial limbs, has so far had limited use in the elderly, but Dr. Kaufman said it might have utility in selected individuals, and he noted that there is at least one commercial device now being marketed.
Many elderly patients will not be candidates for training to reduce falls due to frailty or comorbid conditions that prevent exercise, but Dr. Kaufman encouraged clinicians to evaluate risk of falls in aging individuals who are active because there are strategies to reduce risk, and falls are a major source of morbidity and mortality.
Even for those who are not suitable for risk reduction strategies, testing for risk of falls has the ancillary benefit of raising awareness, according to Dr. Kaufman.
Dr. Kaufman reported no relevant financial relationships to disclose.
NEW ORLEANS – , according to an update on this field at the annual meeting at the Endocrine Society.
“The risk of falling in older adults is very high, but risk can be evaluated, and there are effective strategies for risk reduction,” reported Kenton R. Kaufman, PhD, codirector of the Biomechanics and Motion Analysis Laboratory at the Mayo Clinic, Rochester, Minn.
There is not much debate that aging individuals are at an increased risk of falls, but Dr. Kaufman presented his own set of data to reinforce this point. In a longitudinal study of 125 individuals over the age of 65 years who were followed for a year at his institution, 59% had at least one fall even though all were healthy and functional when enrolled.
“It was more common to fall in summer than in winter, and most occurred on a level surface,” said Dr. Kaufman citing data from a study published 2 years ago (Arch Gerontol Geriatr. 2017;73:240-7). About half of the falls occurred at home.
Only 20%-30% of falls lead to moderate to severe injuries, but this is enough to make fall prevention an appropriate and important focus of public health initiatives to reduce morbidity and lower health costs, according to Dr. Kaufman, citing data suggesting that the medical costs total in the billions of dollars.
As a result of a substantial body of research in this area, there are now multiple clinical tests, such as grip strength, the functional reach test, and the 5-minute walk, that provide some degree of predictive value for identifying elderly individuals at risk for falls.
In addition, simple questionnaires that measure the fear of falling, such as the Activities-Specific Balance Confidence Scale (ABC test), and the Falls Efficacy Scale, also identify individuals at higher risk of falling. According to Dr. Kaufman, the predictive value of these questionnaires stems from the fact that those with more fears are more likely to fall.
Dr. Kaufman advised using these simple measures alone or in combination to screen aging patients for risk of failing. Although he singled out grip strength and the ABC test as the clinical test and the questionnaire he is most likely to employ, he believes others are also reasonable. When performed by primary care physicians, although not specialists, evaluating patients for risk of falling is Medicare-reimbursable, according to Dr. Kaufman.
There are two components to effective prophylaxis. One is improving muscle strength. The other is improving neuromuscular response, which means moving quickly enough to compensate when one’s center of gravity is disturbed. According to Dr. Kaufman, who cited two randomized trials, exercise to restore muscle strength can by itself reduce the risk of falling by 10%-20%.
Neuromuscular training is more intensive and not widely available but very effective. This involves training patients to improve their reaction time in the event of an impending fall. This approach, called postural perturbation training, employs a harness to prevent injury.
“The elderly can lose their facility for rapid recovery but this can be relearned,” said Dr. Kaufman, who cited another two randomized trials with this approach that reduced falls by 45% and 55%.
Postural perturbation training, although used to train amputees to gain comfort ambulating on artificial limbs, has so far had limited use in the elderly, but Dr. Kaufman said it might have utility in selected individuals, and he noted that there is at least one commercial device now being marketed.
Many elderly patients will not be candidates for training to reduce falls due to frailty or comorbid conditions that prevent exercise, but Dr. Kaufman encouraged clinicians to evaluate risk of falls in aging individuals who are active because there are strategies to reduce risk, and falls are a major source of morbidity and mortality.
Even for those who are not suitable for risk reduction strategies, testing for risk of falls has the ancillary benefit of raising awareness, according to Dr. Kaufman.
Dr. Kaufman reported no relevant financial relationships to disclose.
REPORTING FROM ENDO 2019
Patient selection for acute stroke thrombectomy stirs controversy
HONOLULU – A little more than a year ago, results from the DAWN and DEFUSE 3 trials substantially broadened the time window for endovascular thrombectomy of acute ischemic stroke by selecting patients using brain imaging. Stroke clinicians are now trying to reconcile widespread, routine use of this life-changing treatment against an uncertain need to replicate the higher-end perfusion CT and analytical software imaging that these landmark trials used for patient selection. This has produced a schism in what experts advise for using endovascular thrombectomy on acute ischemic stroke patients.
“Go open the artery, people!” Michael D. Hill, MD, exhorted during a talk at the International Stroke Conference, sponsored by the American Heart Association. “Don’t get over-selective; more people will benefit than you think,” said Dr. Hill, a professor of clinical neurosciences at the University of Calgary (Alta.).
“We are over-selecting, and depriving patients,” commented Raul C. Nogueira, MD, professor of neurology at Emory University in Atlanta and a lead investigator of the DAWN trial, speaking from the audience during a discussion at the session where Dr. Hill spoke.
“The prevalence of treatable [acute ischemic stroke] patients is far higher than the prevalence of patients who are not good candidates, so you just want to exclude the ‘wipe-outs’; that’s what we do,” Dr. Hill explained. “Fortunately, endovascular therapy is very safe, and you’re not going to harm many patients. With other treatments [used routinely in medicine] some patients don’t benefit, but when you have a large effect size we use the treatment on almost everyone. The effect size from thrombectomy is so large it’s an argument to treat almost everyone, although the patients in the trials were selected by imaging.”
Dr. Hill repeatedly stressed that for most patients a non-contrast CT image is usually adequate to identify patients with salvageable brain tissue and a low risk for hemorrhage from intervention, and he endorsed also doing CT angiography to further inform the diagnosis. But he dismissed CT perfusion imaging as unnecessary. “Noncontrast CT and CT angiography are more than adequate to make treatment decisions,” he said. “The prevalence of poor collaterals is quite low, about 10%,” which means that about 90% of acute ischemic stroke patients will have more slowly progressing infarction,” making them amenable to treatment in an expanded time window and boosting the volume of salvageable tissue.
But these appeals for more liberal use of thrombectomy without the perfusion CT imaging used in DAWN (N Engl J Med. 2018 Jan 4;378[1]:11-21)and DEFUSE-3 (N Engl J Med. 2018 Feb 22;378[8]:708-18) received push back. Maarten G. Lansberg, MD, a co-investigator on the DEFUSE 3 trial, highlighted the speed and simplicity of CT perfusion imaging, and its utility in helping to better target thrombectomy to the right patients. It’s “speedy, simple, and safe,” it “excludes patients who will not benefit” from thrombectomy, and it helps when the patient’s history and noncontrast CT images are inconclusive, said Dr. Lansberg, a neurologist at Stanford (Calif.) University.
“Clinical presentation will only tell you so much.” With imaging that includes CT perfusion, “you can find out, in 5, 10 minutes, whether there is an occlusion, its location, the extent of dead tissue – that’s all really helpful,” said Marc Fisher, MD, professor of neurology at Harvard Medical School in Boston. “There is a tension now between doing treatment really fast and the concept of slow and fast evolvers. For slow evolvers, the concern about speed is irrelevant because it can take days” for their brains to have substantial damage. “For the fast evolvers, time matters, but they could also possibly be harmed; that’s why we need more data.”
A pitch for more data also came from Pooja Khatri, MD, who also spoke at the session. “There is a real tension now between personalizing the imaging and figuring out exactly the right patients against the time trade off for doing that. Some argue to keep it simple and move fast, and by doing that you’ll wash out any difference from doing more fancy stuff. Plus some places, even in developed countries, can’t afford the image-processing software” used in the DAWN and DEFUSE 3 trials. The correct approach remains unclear and has created “an area ripe for a trial,” declared Dr. Khatri, professor of neurology at director of acute stroke at the University of Cincinnati.
Dr. Hill has received honoraria from Merck and received research funding from Boehringer Ingelheim, Covidien, Medtronic, and Stryker. He has an ownership interest in Calgary Scientific and holds a patent on acute stroke triage methods. Dr. Nogueira has financial relationships with many companies. Dr. Lansberg and Dr. Fisher had no disclosures. Dr. Khatri has been a consultant to Lumosa and has received research funding from Cerenovus/Johnson & Johnson, Genentech, and Nervive.
HONOLULU – A little more than a year ago, results from the DAWN and DEFUSE 3 trials substantially broadened the time window for endovascular thrombectomy of acute ischemic stroke by selecting patients using brain imaging. Stroke clinicians are now trying to reconcile widespread, routine use of this life-changing treatment against an uncertain need to replicate the higher-end perfusion CT and analytical software imaging that these landmark trials used for patient selection. This has produced a schism in what experts advise for using endovascular thrombectomy on acute ischemic stroke patients.
“Go open the artery, people!” Michael D. Hill, MD, exhorted during a talk at the International Stroke Conference, sponsored by the American Heart Association. “Don’t get over-selective; more people will benefit than you think,” said Dr. Hill, a professor of clinical neurosciences at the University of Calgary (Alta.).
“We are over-selecting, and depriving patients,” commented Raul C. Nogueira, MD, professor of neurology at Emory University in Atlanta and a lead investigator of the DAWN trial, speaking from the audience during a discussion at the session where Dr. Hill spoke.
“The prevalence of treatable [acute ischemic stroke] patients is far higher than the prevalence of patients who are not good candidates, so you just want to exclude the ‘wipe-outs’; that’s what we do,” Dr. Hill explained. “Fortunately, endovascular therapy is very safe, and you’re not going to harm many patients. With other treatments [used routinely in medicine] some patients don’t benefit, but when you have a large effect size we use the treatment on almost everyone. The effect size from thrombectomy is so large it’s an argument to treat almost everyone, although the patients in the trials were selected by imaging.”
Dr. Hill repeatedly stressed that for most patients a non-contrast CT image is usually adequate to identify patients with salvageable brain tissue and a low risk for hemorrhage from intervention, and he endorsed also doing CT angiography to further inform the diagnosis. But he dismissed CT perfusion imaging as unnecessary. “Noncontrast CT and CT angiography are more than adequate to make treatment decisions,” he said. “The prevalence of poor collaterals is quite low, about 10%,” which means that about 90% of acute ischemic stroke patients will have more slowly progressing infarction,” making them amenable to treatment in an expanded time window and boosting the volume of salvageable tissue.
But these appeals for more liberal use of thrombectomy without the perfusion CT imaging used in DAWN (N Engl J Med. 2018 Jan 4;378[1]:11-21)and DEFUSE-3 (N Engl J Med. 2018 Feb 22;378[8]:708-18) received push back. Maarten G. Lansberg, MD, a co-investigator on the DEFUSE 3 trial, highlighted the speed and simplicity of CT perfusion imaging, and its utility in helping to better target thrombectomy to the right patients. It’s “speedy, simple, and safe,” it “excludes patients who will not benefit” from thrombectomy, and it helps when the patient’s history and noncontrast CT images are inconclusive, said Dr. Lansberg, a neurologist at Stanford (Calif.) University.
“Clinical presentation will only tell you so much.” With imaging that includes CT perfusion, “you can find out, in 5, 10 minutes, whether there is an occlusion, its location, the extent of dead tissue – that’s all really helpful,” said Marc Fisher, MD, professor of neurology at Harvard Medical School in Boston. “There is a tension now between doing treatment really fast and the concept of slow and fast evolvers. For slow evolvers, the concern about speed is irrelevant because it can take days” for their brains to have substantial damage. “For the fast evolvers, time matters, but they could also possibly be harmed; that’s why we need more data.”
A pitch for more data also came from Pooja Khatri, MD, who also spoke at the session. “There is a real tension now between personalizing the imaging and figuring out exactly the right patients against the time trade off for doing that. Some argue to keep it simple and move fast, and by doing that you’ll wash out any difference from doing more fancy stuff. Plus some places, even in developed countries, can’t afford the image-processing software” used in the DAWN and DEFUSE 3 trials. The correct approach remains unclear and has created “an area ripe for a trial,” declared Dr. Khatri, professor of neurology at director of acute stroke at the University of Cincinnati.
Dr. Hill has received honoraria from Merck and received research funding from Boehringer Ingelheim, Covidien, Medtronic, and Stryker. He has an ownership interest in Calgary Scientific and holds a patent on acute stroke triage methods. Dr. Nogueira has financial relationships with many companies. Dr. Lansberg and Dr. Fisher had no disclosures. Dr. Khatri has been a consultant to Lumosa and has received research funding from Cerenovus/Johnson & Johnson, Genentech, and Nervive.
HONOLULU – A little more than a year ago, results from the DAWN and DEFUSE 3 trials substantially broadened the time window for endovascular thrombectomy of acute ischemic stroke by selecting patients using brain imaging. Stroke clinicians are now trying to reconcile widespread, routine use of this life-changing treatment against an uncertain need to replicate the higher-end perfusion CT and analytical software imaging that these landmark trials used for patient selection. This has produced a schism in what experts advise for using endovascular thrombectomy on acute ischemic stroke patients.
“Go open the artery, people!” Michael D. Hill, MD, exhorted during a talk at the International Stroke Conference, sponsored by the American Heart Association. “Don’t get over-selective; more people will benefit than you think,” said Dr. Hill, a professor of clinical neurosciences at the University of Calgary (Alta.).
“We are over-selecting, and depriving patients,” commented Raul C. Nogueira, MD, professor of neurology at Emory University in Atlanta and a lead investigator of the DAWN trial, speaking from the audience during a discussion at the session where Dr. Hill spoke.
“The prevalence of treatable [acute ischemic stroke] patients is far higher than the prevalence of patients who are not good candidates, so you just want to exclude the ‘wipe-outs’; that’s what we do,” Dr. Hill explained. “Fortunately, endovascular therapy is very safe, and you’re not going to harm many patients. With other treatments [used routinely in medicine] some patients don’t benefit, but when you have a large effect size we use the treatment on almost everyone. The effect size from thrombectomy is so large it’s an argument to treat almost everyone, although the patients in the trials were selected by imaging.”
Dr. Hill repeatedly stressed that for most patients a non-contrast CT image is usually adequate to identify patients with salvageable brain tissue and a low risk for hemorrhage from intervention, and he endorsed also doing CT angiography to further inform the diagnosis. But he dismissed CT perfusion imaging as unnecessary. “Noncontrast CT and CT angiography are more than adequate to make treatment decisions,” he said. “The prevalence of poor collaterals is quite low, about 10%,” which means that about 90% of acute ischemic stroke patients will have more slowly progressing infarction,” making them amenable to treatment in an expanded time window and boosting the volume of salvageable tissue.
But these appeals for more liberal use of thrombectomy without the perfusion CT imaging used in DAWN (N Engl J Med. 2018 Jan 4;378[1]:11-21)and DEFUSE-3 (N Engl J Med. 2018 Feb 22;378[8]:708-18) received push back. Maarten G. Lansberg, MD, a co-investigator on the DEFUSE 3 trial, highlighted the speed and simplicity of CT perfusion imaging, and its utility in helping to better target thrombectomy to the right patients. It’s “speedy, simple, and safe,” it “excludes patients who will not benefit” from thrombectomy, and it helps when the patient’s history and noncontrast CT images are inconclusive, said Dr. Lansberg, a neurologist at Stanford (Calif.) University.
“Clinical presentation will only tell you so much.” With imaging that includes CT perfusion, “you can find out, in 5, 10 minutes, whether there is an occlusion, its location, the extent of dead tissue – that’s all really helpful,” said Marc Fisher, MD, professor of neurology at Harvard Medical School in Boston. “There is a tension now between doing treatment really fast and the concept of slow and fast evolvers. For slow evolvers, the concern about speed is irrelevant because it can take days” for their brains to have substantial damage. “For the fast evolvers, time matters, but they could also possibly be harmed; that’s why we need more data.”
A pitch for more data also came from Pooja Khatri, MD, who also spoke at the session. “There is a real tension now between personalizing the imaging and figuring out exactly the right patients against the time trade off for doing that. Some argue to keep it simple and move fast, and by doing that you’ll wash out any difference from doing more fancy stuff. Plus some places, even in developed countries, can’t afford the image-processing software” used in the DAWN and DEFUSE 3 trials. The correct approach remains unclear and has created “an area ripe for a trial,” declared Dr. Khatri, professor of neurology at director of acute stroke at the University of Cincinnati.
Dr. Hill has received honoraria from Merck and received research funding from Boehringer Ingelheim, Covidien, Medtronic, and Stryker. He has an ownership interest in Calgary Scientific and holds a patent on acute stroke triage methods. Dr. Nogueira has financial relationships with many companies. Dr. Lansberg and Dr. Fisher had no disclosures. Dr. Khatri has been a consultant to Lumosa and has received research funding from Cerenovus/Johnson & Johnson, Genentech, and Nervive.
REPORTING FROM ISC 2019
Brachytherapy access may mediate poor cervical cancer survival in blacks
HONOLULU – , according to a speaker at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
Stephanie Alimena, MD, of Brigham and Women’s Hospital in Boston, presented a large, retrospective study showing that use of brachytherapy mediated survival differences by race.
In the absence of brachytherapy, black patients had a significantly higher risk of death than did non-black patients (P = .013). However, when brachytherapy was used, black and non-black patients had a similar risk of death (P = .83).
“[W]e know that use of a brachytherapy boost is associated with improved patient outcomes, including improved cancer-specific and overall survival,” Dr. Alimena said. “We also know that African-American women have one of the highest incidences of cervical cancer in the United States and also have worse mortality from cervical cancer.”
“Studies have reached varying conclusions about the impact of race on brachytherapy utilization, with several smaller studies suggesting that minority women may be less likely to receive brachytherapy services compared to white women. No studies have specifically examined the interaction between race, radiation, and survival.”
Dr. Alimena and her colleagues decided to examine the interaction using data from the National Cancer Database. The researchers evaluated 15,411 women diagnosed with cervical cancer from 2004 to 2014. The patients had stage IB2 to IVA disease, their mean age was 54 years (range, 19-90), 58% had received brachytherapy, and 19% were black.
“Race was defined as black or non-black race, given that previous data had shown similar and even increased survival rates for Hispanic and Asian-American women compared to white patients diagnosed with cervical cancer,” Dr. Alimena noted.
Differences by race
The researchers found that black patients were significantly less likely to receive brachytherapy than were non-black patients: 52.5% vs. 59.0%, respectively (P less than .001).
Black patients were significantly more likely to have stage III disease (42.7% vs. 37.6%; P less than .001) and less likely to have stage IVA disease (6.8% vs. 7.3%; P less than .001).
Black patients were significantly more likely to have government insurance (57.0% vs. 49.1%; P less than .001) and less likely to have private insurance (27.6% vs. 36.7%; P less than .001).
And black patients were significantly more likely to have annual incomes below $38,000 (49.4% vs. 22.6%; P less than .001).
Factors associated with brachytherapy
In a multivariate analysis, black race was significantly associated with a reduced likelihood of receiving brachytherapy. The odds ratio (OR) was 0.86 (P = .003).
Other factors significantly associated with a reduced likelihood of receiving brachytherapy were:
- Being older than 70 years (OR = 0.59; P less than .001)
- Having government insurance (OR = 0.89; P = .008) or no insurance/unknown insurance status (OR = 0.75; P less than .001)
- Having stage III disease (OR = 0.47; P less than .001) or stage IVA disease (OR = 0.20; P less than .001)
- Being treated in southern states (OR = 0.67; P less than .001) or western states (OR = 0.86; P = .02)
- Having a Charlson/Deyo score of 2 or more (OR = 0.73; P less than .001).
Race, brachytherapy, and survival
“Consistent with prior data, we found that black patients had a significant decrease in overall survival, compared to non-black women,” Dr. Alimena said. “Furthermore, we found survival differences by race were mediated by brachytherapy use.”
The median overall survival was 52.5 months among black patients and 65.3 months among non-black patients (P less than .001).
Among patients who did not receive brachytherapy, black patients had a significantly higher risk of death than non-black patients (adjusted hazard ratio = 1.11; P = .013).
However, among patients who did receive brachytherapy, black and non-black patients had a similar risk of death (adjusted hazard ratio = 1.01; P = .83). The interaction term comparing these survival curves was statistically significant (P = .043).
“This is the first study, to our knowledge, to show such an interaction between race and survival being mediated by one particular treatment modality,” Dr. Alimena said.
“While not directly tested in this study, the most likely hypothesis why black patients may be less likely to receive brachytherapy is having poor access to brachytherapy services. This suggests that reducing racial disparities in survival is possible by increasing access to brachytherapy for black patients.”
Dr. Alimena had no financial disclosures.
SOURCE: Alimena S et al. SGO 2019. Abstract 11.
HONOLULU – , according to a speaker at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
Stephanie Alimena, MD, of Brigham and Women’s Hospital in Boston, presented a large, retrospective study showing that use of brachytherapy mediated survival differences by race.
In the absence of brachytherapy, black patients had a significantly higher risk of death than did non-black patients (P = .013). However, when brachytherapy was used, black and non-black patients had a similar risk of death (P = .83).
“[W]e know that use of a brachytherapy boost is associated with improved patient outcomes, including improved cancer-specific and overall survival,” Dr. Alimena said. “We also know that African-American women have one of the highest incidences of cervical cancer in the United States and also have worse mortality from cervical cancer.”
“Studies have reached varying conclusions about the impact of race on brachytherapy utilization, with several smaller studies suggesting that minority women may be less likely to receive brachytherapy services compared to white women. No studies have specifically examined the interaction between race, radiation, and survival.”
Dr. Alimena and her colleagues decided to examine the interaction using data from the National Cancer Database. The researchers evaluated 15,411 women diagnosed with cervical cancer from 2004 to 2014. The patients had stage IB2 to IVA disease, their mean age was 54 years (range, 19-90), 58% had received brachytherapy, and 19% were black.
“Race was defined as black or non-black race, given that previous data had shown similar and even increased survival rates for Hispanic and Asian-American women compared to white patients diagnosed with cervical cancer,” Dr. Alimena noted.
Differences by race
The researchers found that black patients were significantly less likely to receive brachytherapy than were non-black patients: 52.5% vs. 59.0%, respectively (P less than .001).
Black patients were significantly more likely to have stage III disease (42.7% vs. 37.6%; P less than .001) and less likely to have stage IVA disease (6.8% vs. 7.3%; P less than .001).
Black patients were significantly more likely to have government insurance (57.0% vs. 49.1%; P less than .001) and less likely to have private insurance (27.6% vs. 36.7%; P less than .001).
And black patients were significantly more likely to have annual incomes below $38,000 (49.4% vs. 22.6%; P less than .001).
Factors associated with brachytherapy
In a multivariate analysis, black race was significantly associated with a reduced likelihood of receiving brachytherapy. The odds ratio (OR) was 0.86 (P = .003).
Other factors significantly associated with a reduced likelihood of receiving brachytherapy were:
- Being older than 70 years (OR = 0.59; P less than .001)
- Having government insurance (OR = 0.89; P = .008) or no insurance/unknown insurance status (OR = 0.75; P less than .001)
- Having stage III disease (OR = 0.47; P less than .001) or stage IVA disease (OR = 0.20; P less than .001)
- Being treated in southern states (OR = 0.67; P less than .001) or western states (OR = 0.86; P = .02)
- Having a Charlson/Deyo score of 2 or more (OR = 0.73; P less than .001).
Race, brachytherapy, and survival
“Consistent with prior data, we found that black patients had a significant decrease in overall survival, compared to non-black women,” Dr. Alimena said. “Furthermore, we found survival differences by race were mediated by brachytherapy use.”
The median overall survival was 52.5 months among black patients and 65.3 months among non-black patients (P less than .001).
Among patients who did not receive brachytherapy, black patients had a significantly higher risk of death than non-black patients (adjusted hazard ratio = 1.11; P = .013).
However, among patients who did receive brachytherapy, black and non-black patients had a similar risk of death (adjusted hazard ratio = 1.01; P = .83). The interaction term comparing these survival curves was statistically significant (P = .043).
“This is the first study, to our knowledge, to show such an interaction between race and survival being mediated by one particular treatment modality,” Dr. Alimena said.
“While not directly tested in this study, the most likely hypothesis why black patients may be less likely to receive brachytherapy is having poor access to brachytherapy services. This suggests that reducing racial disparities in survival is possible by increasing access to brachytherapy for black patients.”
Dr. Alimena had no financial disclosures.
SOURCE: Alimena S et al. SGO 2019. Abstract 11.
HONOLULU – , according to a speaker at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
Stephanie Alimena, MD, of Brigham and Women’s Hospital in Boston, presented a large, retrospective study showing that use of brachytherapy mediated survival differences by race.
In the absence of brachytherapy, black patients had a significantly higher risk of death than did non-black patients (P = .013). However, when brachytherapy was used, black and non-black patients had a similar risk of death (P = .83).
“[W]e know that use of a brachytherapy boost is associated with improved patient outcomes, including improved cancer-specific and overall survival,” Dr. Alimena said. “We also know that African-American women have one of the highest incidences of cervical cancer in the United States and also have worse mortality from cervical cancer.”
“Studies have reached varying conclusions about the impact of race on brachytherapy utilization, with several smaller studies suggesting that minority women may be less likely to receive brachytherapy services compared to white women. No studies have specifically examined the interaction between race, radiation, and survival.”
Dr. Alimena and her colleagues decided to examine the interaction using data from the National Cancer Database. The researchers evaluated 15,411 women diagnosed with cervical cancer from 2004 to 2014. The patients had stage IB2 to IVA disease, their mean age was 54 years (range, 19-90), 58% had received brachytherapy, and 19% were black.
“Race was defined as black or non-black race, given that previous data had shown similar and even increased survival rates for Hispanic and Asian-American women compared to white patients diagnosed with cervical cancer,” Dr. Alimena noted.
Differences by race
The researchers found that black patients were significantly less likely to receive brachytherapy than were non-black patients: 52.5% vs. 59.0%, respectively (P less than .001).
Black patients were significantly more likely to have stage III disease (42.7% vs. 37.6%; P less than .001) and less likely to have stage IVA disease (6.8% vs. 7.3%; P less than .001).
Black patients were significantly more likely to have government insurance (57.0% vs. 49.1%; P less than .001) and less likely to have private insurance (27.6% vs. 36.7%; P less than .001).
And black patients were significantly more likely to have annual incomes below $38,000 (49.4% vs. 22.6%; P less than .001).
Factors associated with brachytherapy
In a multivariate analysis, black race was significantly associated with a reduced likelihood of receiving brachytherapy. The odds ratio (OR) was 0.86 (P = .003).
Other factors significantly associated with a reduced likelihood of receiving brachytherapy were:
- Being older than 70 years (OR = 0.59; P less than .001)
- Having government insurance (OR = 0.89; P = .008) or no insurance/unknown insurance status (OR = 0.75; P less than .001)
- Having stage III disease (OR = 0.47; P less than .001) or stage IVA disease (OR = 0.20; P less than .001)
- Being treated in southern states (OR = 0.67; P less than .001) or western states (OR = 0.86; P = .02)
- Having a Charlson/Deyo score of 2 or more (OR = 0.73; P less than .001).
Race, brachytherapy, and survival
“Consistent with prior data, we found that black patients had a significant decrease in overall survival, compared to non-black women,” Dr. Alimena said. “Furthermore, we found survival differences by race were mediated by brachytherapy use.”
The median overall survival was 52.5 months among black patients and 65.3 months among non-black patients (P less than .001).
Among patients who did not receive brachytherapy, black patients had a significantly higher risk of death than non-black patients (adjusted hazard ratio = 1.11; P = .013).
However, among patients who did receive brachytherapy, black and non-black patients had a similar risk of death (adjusted hazard ratio = 1.01; P = .83). The interaction term comparing these survival curves was statistically significant (P = .043).
“This is the first study, to our knowledge, to show such an interaction between race and survival being mediated by one particular treatment modality,” Dr. Alimena said.
“While not directly tested in this study, the most likely hypothesis why black patients may be less likely to receive brachytherapy is having poor access to brachytherapy services. This suggests that reducing racial disparities in survival is possible by increasing access to brachytherapy for black patients.”
Dr. Alimena had no financial disclosures.
SOURCE: Alimena S et al. SGO 2019. Abstract 11.
REPORTING FROM SGO 2019
Study explores third-line trabectedin plus PLD for BRCA1/2 ovarian cancer
HONOLULU – Adding trabectedin to pegylated liposomal doxorubicin (PLD) significantly prolongs overall and progression-free survival in BRCA1/2-mutated patients with advanced-relapsed epithelial ovarian cancer after two prior lines of platinum-based therapy, according to prespecified subgroup analyses of a randomized, open-label, phase 3 trial.
Patients with a platinum-free interval (PFI) of 6-12 months also experienced significantly improved progression-free survival (PFS), and those with both a BRCA mutation and PFI of 6-12 months experienced significantly improved overall survival (OS) and PFS with combined trabectedin and PLD vs. PLD alone, Bradley J. Monk, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
Of 576 patients enrolled in the ET743-OVC-3006 trial, 289 received the combination regimen, and 287 received PLD alone. The study completed enrollment but was discontinued on January 18, 2018, after an interim analysis showed the futility threshold for OS and observed toxicity in the combination therapy group was exceeded.
OS was 21.5 and 22.2 months (hazard ratio = 1.13) in the combination and monotherapy groups, respectively. However, the subgroups analysis of patients with a germline BRCA1/2 mutation showed a median OS of 34.2 months with combination therapy and 20.9 months with PLD monotherapy, for a median survival benefit with combination therapy of 13.3 months (HR = 0.54), said Dr. Monk, professor and director of the division of gynecologic oncology at Creighton University School of Medicine, St. Joseph’s Hospital and Medical Center, Phoenix, Ariz.
A subgroup of 60 patients with both a BRCA mutation and a PFI of 6-12 months had even greater improvement in OS with combination therapy when compared with PLD monotherapy (31.5 vs. 14.9 months; HR = 0.37). An effect on PFS was also detected in this subgroup (10.1 vs. 6.1 months; HR = 0.48), he said.
No difference in PFS was found in the overall unselected study population, Dr. Monk said, but among all patients with 6-12-month PFI alone, combination therapy led to significantly longer PFS than with monotherapy (7.5 vs. 5.5 months; HR = 0.72, P = .0388) and a positive trend in OS for the combination group (24.8 vs. 17.4 months; HR = 0.69; P = .565).
“I get it – this suffers from multiple comparisons, and this [analysis] in particular was ad hoc,” he said.
Still, given historical findings with respect to trabectedin in combination with PLD, the findings are provocative, he said.
Trabectedin is “a complicated anticancer cytotoxic medication” approved by the Food and Drug Administration in 2015 based on findings of treatment benefit in liposarcoma and leiomyosarcoma (including uterine leiomyosarcoma), he explained.
The agent has also been studied widely in other tumors, including in ovarian cancer. In the OVA-301 trial, for example, Dr. Monk and his colleagues looked at trabectedin in the second-line setting in patients with recurrent ovarian cancer.
That trial, which met its primary endpoint of an overall PFS benefit with trabectedin and generated the hypothesis that the agent might have particular benefit in BRCA-mutated patients, led to regulatory approval of trabectedin in Europe and elsewhere as an option for treatment in patients with partially platinum-sensitive recurrences – but not in the United States, he said.
Since OVA-301 did not lead to FDA approval, he and his colleagues designed the current study to look more closely at trabectedin with and without PLD, using the same dosing regimens as in OVA-301, but in the third-line setting and using OS as the primary endpoint.
Based on the intriguing OVA-301 findings in BRCA-mutated patients, the BRCA1/2-mutated subgroup analysis in the ET743-OVC-3006 trial was prespecified, he noted.
Study participants were women with advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer who responded to two prior lines of platinum-based therapy and who were at least 6 months platinum-free. They were randomly assigned 1:1 to trabectedin plus PLD or PLD alone. Dosing in the combination arm was 1.1 mg/m2 of intravenous trabectedin over 3 hours and 30 mg/m2 of IV PLD given over 90 minutes every 3 weeks, and in the monotherapy arm PLD was given at a dose of 50 mg/m2 IV over 90 minutes every 4 weeks.
The groups were well balanced with respect to age, race, and performance status, and each included “a smattering of histological subtypes,” he said.
Of the 576 enrolled, 155 were BRCA1 or BRCA2-positive, with about two-thirds carrying a BRCA1 mutation.
Very few were exposed to bevacizumab or poly(ADP ribose) polymerase (PARP) inhibitors, as the study was initiated before those were developed.
Adverse events (AEs) of all grades occurred at similar rates in the two arms and occurred in most patients. Most were drug-related, but grade 3-4 AE rates were higher in the combination arm (79% vs. 54%). Drug-related AEs leading to treatment discontinuation occurred in 32.5% and 16% of the combination and monotherapy arm patients, respectively, Dr. Monk said.
“Most of those treatment-related AEs were cytopenia and/or transaminitis. There were also almost twice as many deaths in the combination arm: 3.5% vs. 1.6%,” he said, adding that the deaths were thought to be related to tumor progression rather than to the drugs.
Although the addition of trabectedin to PLD did not prolong OS, compared with PLD alone in unselected patients with advanced, third-line, recurrent ovarian cancer, the combination does appear to benefit patients with germline BRCA mutations, a 6-12 month platinum-free interval, or both, he said, concluding that “the results of this phase 3 subanalysis are consistent with the previous observations in OVA-301 that trabectedin alone or with PLD displays selective antitumor activity in this BRCA subgroup.
“It adds more toxicity, but no new safety signals were identified,” he added.
Asked during a panel discussion if he thinks these results mark “then end of the road” for trabectedin, Dr. Monk said he does not.
“I don’t think we should be penalized because we enrolled all those non-BRCA patients. When you look at the BRCA cohort I think there is an opportunity to get this to our patients,” he said, noting that “the major challenge” is that those patients had not been given a PARP inhibitor. “So I think that there might be an opportunity for licensing, but the confirmatory trial would have to [look at whether] the drug still works after failure of a PARP.”
The ET743-OVC-3006 trial was sponsored by Janssen Research & Development. Dr. Monk reported financial relationships (consulting, honoraria/reimbursement, and/or speaker’s bureau participation) with Janssen/Johnson & Johnson and more than 20 other pharmaceutical companies.
SOURCE: Monk B et al., SGO 2019: Abstract 20.
HONOLULU – Adding trabectedin to pegylated liposomal doxorubicin (PLD) significantly prolongs overall and progression-free survival in BRCA1/2-mutated patients with advanced-relapsed epithelial ovarian cancer after two prior lines of platinum-based therapy, according to prespecified subgroup analyses of a randomized, open-label, phase 3 trial.
Patients with a platinum-free interval (PFI) of 6-12 months also experienced significantly improved progression-free survival (PFS), and those with both a BRCA mutation and PFI of 6-12 months experienced significantly improved overall survival (OS) and PFS with combined trabectedin and PLD vs. PLD alone, Bradley J. Monk, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
Of 576 patients enrolled in the ET743-OVC-3006 trial, 289 received the combination regimen, and 287 received PLD alone. The study completed enrollment but was discontinued on January 18, 2018, after an interim analysis showed the futility threshold for OS and observed toxicity in the combination therapy group was exceeded.
OS was 21.5 and 22.2 months (hazard ratio = 1.13) in the combination and monotherapy groups, respectively. However, the subgroups analysis of patients with a germline BRCA1/2 mutation showed a median OS of 34.2 months with combination therapy and 20.9 months with PLD monotherapy, for a median survival benefit with combination therapy of 13.3 months (HR = 0.54), said Dr. Monk, professor and director of the division of gynecologic oncology at Creighton University School of Medicine, St. Joseph’s Hospital and Medical Center, Phoenix, Ariz.
A subgroup of 60 patients with both a BRCA mutation and a PFI of 6-12 months had even greater improvement in OS with combination therapy when compared with PLD monotherapy (31.5 vs. 14.9 months; HR = 0.37). An effect on PFS was also detected in this subgroup (10.1 vs. 6.1 months; HR = 0.48), he said.
No difference in PFS was found in the overall unselected study population, Dr. Monk said, but among all patients with 6-12-month PFI alone, combination therapy led to significantly longer PFS than with monotherapy (7.5 vs. 5.5 months; HR = 0.72, P = .0388) and a positive trend in OS for the combination group (24.8 vs. 17.4 months; HR = 0.69; P = .565).
“I get it – this suffers from multiple comparisons, and this [analysis] in particular was ad hoc,” he said.
Still, given historical findings with respect to trabectedin in combination with PLD, the findings are provocative, he said.
Trabectedin is “a complicated anticancer cytotoxic medication” approved by the Food and Drug Administration in 2015 based on findings of treatment benefit in liposarcoma and leiomyosarcoma (including uterine leiomyosarcoma), he explained.
The agent has also been studied widely in other tumors, including in ovarian cancer. In the OVA-301 trial, for example, Dr. Monk and his colleagues looked at trabectedin in the second-line setting in patients with recurrent ovarian cancer.
That trial, which met its primary endpoint of an overall PFS benefit with trabectedin and generated the hypothesis that the agent might have particular benefit in BRCA-mutated patients, led to regulatory approval of trabectedin in Europe and elsewhere as an option for treatment in patients with partially platinum-sensitive recurrences – but not in the United States, he said.
Since OVA-301 did not lead to FDA approval, he and his colleagues designed the current study to look more closely at trabectedin with and without PLD, using the same dosing regimens as in OVA-301, but in the third-line setting and using OS as the primary endpoint.
Based on the intriguing OVA-301 findings in BRCA-mutated patients, the BRCA1/2-mutated subgroup analysis in the ET743-OVC-3006 trial was prespecified, he noted.
Study participants were women with advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer who responded to two prior lines of platinum-based therapy and who were at least 6 months platinum-free. They were randomly assigned 1:1 to trabectedin plus PLD or PLD alone. Dosing in the combination arm was 1.1 mg/m2 of intravenous trabectedin over 3 hours and 30 mg/m2 of IV PLD given over 90 minutes every 3 weeks, and in the monotherapy arm PLD was given at a dose of 50 mg/m2 IV over 90 minutes every 4 weeks.
The groups were well balanced with respect to age, race, and performance status, and each included “a smattering of histological subtypes,” he said.
Of the 576 enrolled, 155 were BRCA1 or BRCA2-positive, with about two-thirds carrying a BRCA1 mutation.
Very few were exposed to bevacizumab or poly(ADP ribose) polymerase (PARP) inhibitors, as the study was initiated before those were developed.
Adverse events (AEs) of all grades occurred at similar rates in the two arms and occurred in most patients. Most were drug-related, but grade 3-4 AE rates were higher in the combination arm (79% vs. 54%). Drug-related AEs leading to treatment discontinuation occurred in 32.5% and 16% of the combination and monotherapy arm patients, respectively, Dr. Monk said.
“Most of those treatment-related AEs were cytopenia and/or transaminitis. There were also almost twice as many deaths in the combination arm: 3.5% vs. 1.6%,” he said, adding that the deaths were thought to be related to tumor progression rather than to the drugs.
Although the addition of trabectedin to PLD did not prolong OS, compared with PLD alone in unselected patients with advanced, third-line, recurrent ovarian cancer, the combination does appear to benefit patients with germline BRCA mutations, a 6-12 month platinum-free interval, or both, he said, concluding that “the results of this phase 3 subanalysis are consistent with the previous observations in OVA-301 that trabectedin alone or with PLD displays selective antitumor activity in this BRCA subgroup.
“It adds more toxicity, but no new safety signals were identified,” he added.
Asked during a panel discussion if he thinks these results mark “then end of the road” for trabectedin, Dr. Monk said he does not.
“I don’t think we should be penalized because we enrolled all those non-BRCA patients. When you look at the BRCA cohort I think there is an opportunity to get this to our patients,” he said, noting that “the major challenge” is that those patients had not been given a PARP inhibitor. “So I think that there might be an opportunity for licensing, but the confirmatory trial would have to [look at whether] the drug still works after failure of a PARP.”
The ET743-OVC-3006 trial was sponsored by Janssen Research & Development. Dr. Monk reported financial relationships (consulting, honoraria/reimbursement, and/or speaker’s bureau participation) with Janssen/Johnson & Johnson and more than 20 other pharmaceutical companies.
SOURCE: Monk B et al., SGO 2019: Abstract 20.
HONOLULU – Adding trabectedin to pegylated liposomal doxorubicin (PLD) significantly prolongs overall and progression-free survival in BRCA1/2-mutated patients with advanced-relapsed epithelial ovarian cancer after two prior lines of platinum-based therapy, according to prespecified subgroup analyses of a randomized, open-label, phase 3 trial.
Patients with a platinum-free interval (PFI) of 6-12 months also experienced significantly improved progression-free survival (PFS), and those with both a BRCA mutation and PFI of 6-12 months experienced significantly improved overall survival (OS) and PFS with combined trabectedin and PLD vs. PLD alone, Bradley J. Monk, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
Of 576 patients enrolled in the ET743-OVC-3006 trial, 289 received the combination regimen, and 287 received PLD alone. The study completed enrollment but was discontinued on January 18, 2018, after an interim analysis showed the futility threshold for OS and observed toxicity in the combination therapy group was exceeded.
OS was 21.5 and 22.2 months (hazard ratio = 1.13) in the combination and monotherapy groups, respectively. However, the subgroups analysis of patients with a germline BRCA1/2 mutation showed a median OS of 34.2 months with combination therapy and 20.9 months with PLD monotherapy, for a median survival benefit with combination therapy of 13.3 months (HR = 0.54), said Dr. Monk, professor and director of the division of gynecologic oncology at Creighton University School of Medicine, St. Joseph’s Hospital and Medical Center, Phoenix, Ariz.
A subgroup of 60 patients with both a BRCA mutation and a PFI of 6-12 months had even greater improvement in OS with combination therapy when compared with PLD monotherapy (31.5 vs. 14.9 months; HR = 0.37). An effect on PFS was also detected in this subgroup (10.1 vs. 6.1 months; HR = 0.48), he said.
No difference in PFS was found in the overall unselected study population, Dr. Monk said, but among all patients with 6-12-month PFI alone, combination therapy led to significantly longer PFS than with monotherapy (7.5 vs. 5.5 months; HR = 0.72, P = .0388) and a positive trend in OS for the combination group (24.8 vs. 17.4 months; HR = 0.69; P = .565).
“I get it – this suffers from multiple comparisons, and this [analysis] in particular was ad hoc,” he said.
Still, given historical findings with respect to trabectedin in combination with PLD, the findings are provocative, he said.
Trabectedin is “a complicated anticancer cytotoxic medication” approved by the Food and Drug Administration in 2015 based on findings of treatment benefit in liposarcoma and leiomyosarcoma (including uterine leiomyosarcoma), he explained.
The agent has also been studied widely in other tumors, including in ovarian cancer. In the OVA-301 trial, for example, Dr. Monk and his colleagues looked at trabectedin in the second-line setting in patients with recurrent ovarian cancer.
That trial, which met its primary endpoint of an overall PFS benefit with trabectedin and generated the hypothesis that the agent might have particular benefit in BRCA-mutated patients, led to regulatory approval of trabectedin in Europe and elsewhere as an option for treatment in patients with partially platinum-sensitive recurrences – but not in the United States, he said.
Since OVA-301 did not lead to FDA approval, he and his colleagues designed the current study to look more closely at trabectedin with and without PLD, using the same dosing regimens as in OVA-301, but in the third-line setting and using OS as the primary endpoint.
Based on the intriguing OVA-301 findings in BRCA-mutated patients, the BRCA1/2-mutated subgroup analysis in the ET743-OVC-3006 trial was prespecified, he noted.
Study participants were women with advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer who responded to two prior lines of platinum-based therapy and who were at least 6 months platinum-free. They were randomly assigned 1:1 to trabectedin plus PLD or PLD alone. Dosing in the combination arm was 1.1 mg/m2 of intravenous trabectedin over 3 hours and 30 mg/m2 of IV PLD given over 90 minutes every 3 weeks, and in the monotherapy arm PLD was given at a dose of 50 mg/m2 IV over 90 minutes every 4 weeks.
The groups were well balanced with respect to age, race, and performance status, and each included “a smattering of histological subtypes,” he said.
Of the 576 enrolled, 155 were BRCA1 or BRCA2-positive, with about two-thirds carrying a BRCA1 mutation.
Very few were exposed to bevacizumab or poly(ADP ribose) polymerase (PARP) inhibitors, as the study was initiated before those were developed.
Adverse events (AEs) of all grades occurred at similar rates in the two arms and occurred in most patients. Most were drug-related, but grade 3-4 AE rates were higher in the combination arm (79% vs. 54%). Drug-related AEs leading to treatment discontinuation occurred in 32.5% and 16% of the combination and monotherapy arm patients, respectively, Dr. Monk said.
“Most of those treatment-related AEs were cytopenia and/or transaminitis. There were also almost twice as many deaths in the combination arm: 3.5% vs. 1.6%,” he said, adding that the deaths were thought to be related to tumor progression rather than to the drugs.
Although the addition of trabectedin to PLD did not prolong OS, compared with PLD alone in unselected patients with advanced, third-line, recurrent ovarian cancer, the combination does appear to benefit patients with germline BRCA mutations, a 6-12 month platinum-free interval, or both, he said, concluding that “the results of this phase 3 subanalysis are consistent with the previous observations in OVA-301 that trabectedin alone or with PLD displays selective antitumor activity in this BRCA subgroup.
“It adds more toxicity, but no new safety signals were identified,” he added.
Asked during a panel discussion if he thinks these results mark “then end of the road” for trabectedin, Dr. Monk said he does not.
“I don’t think we should be penalized because we enrolled all those non-BRCA patients. When you look at the BRCA cohort I think there is an opportunity to get this to our patients,” he said, noting that “the major challenge” is that those patients had not been given a PARP inhibitor. “So I think that there might be an opportunity for licensing, but the confirmatory trial would have to [look at whether] the drug still works after failure of a PARP.”
The ET743-OVC-3006 trial was sponsored by Janssen Research & Development. Dr. Monk reported financial relationships (consulting, honoraria/reimbursement, and/or speaker’s bureau participation) with Janssen/Johnson & Johnson and more than 20 other pharmaceutical companies.
SOURCE: Monk B et al., SGO 2019: Abstract 20.
REPORTING FROM SGO 2019
No birth rate gains from levothyroxine in pregnancy
Treatment with levothyroxine does not improve the live birth rate in women with thyroid peroxidase antibodies before conception, according to data presented at the annual meeting of the Endocrine Society.
Until now, the evidence for the use of levothyroxine in pregnant women with thyroid peroxidase antibodies but normal thyroid function has been inconclusive, Rima K. Dhillon-Smith, MBChB, PhD, of the University of Birmingham (England), and her coauthors said in a paper published simultaneously with the meeting presentation March 23 in the New England Journal of Medicine.
Previous studies have shown that women with thyroid peroxidase antibodies but normal thyroid function have a nearly fourfold higher risk of miscarriage and twofold higher risk of preterm birth, compared with women who don’t have the antibodies.
In the new double-blind study, 952 women with thyroid peroxidase antibodies, normal thyroid function, and a history of miscarriage or infertility were randomized either to daily 50 mcg levothyroxine or placebo, taken from conception to the end of pregnancy.
The rate of pregnancy was similar in the levothyroxine and placebo groups (56.6% vs. 58.3%, respectively), as was the live birth rate (37.4% vs. 37.9%), despite the observation that the levothyroxine group had consistently lower serum thyrotropin and higher free T4 concentrations than did the placebo group.
There were also no significant differences between the two groups in secondary outcomes of miscarriage, preterm birth, or neonatal outcomes such as birth weight.
Researchers also saw no statistically significant differences in the rate of serious adverse events or in the number of women who showed abnormal results on thyroid function tests.
The authors noted that the dosage of levothyroxine used in the study was fixed, leaving the possibility that “the dose may need to be adjusted depending on the participant’s body weight, thyroid peroxidase antibody level, or thyrotropin concentration.”
Existing guidelines from the American Thyroid Association acknowledge the lack of evidence in favor of levothyroxine decreasing the risk of pregnancy loss. However, the guidelines also state that it can be considered in antibody-positive, euthyroid women with a history of loss, “given its potential benefits in comparison with its minimal risk.”
The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
SOURCE: Dhillon-Smith R et al. N Engl J Med. 2019 March 23. doi: 10.1056/NEJMoa1812537
Treatment with levothyroxine does not improve the live birth rate in women with thyroid peroxidase antibodies before conception, according to data presented at the annual meeting of the Endocrine Society.
Until now, the evidence for the use of levothyroxine in pregnant women with thyroid peroxidase antibodies but normal thyroid function has been inconclusive, Rima K. Dhillon-Smith, MBChB, PhD, of the University of Birmingham (England), and her coauthors said in a paper published simultaneously with the meeting presentation March 23 in the New England Journal of Medicine.
Previous studies have shown that women with thyroid peroxidase antibodies but normal thyroid function have a nearly fourfold higher risk of miscarriage and twofold higher risk of preterm birth, compared with women who don’t have the antibodies.
In the new double-blind study, 952 women with thyroid peroxidase antibodies, normal thyroid function, and a history of miscarriage or infertility were randomized either to daily 50 mcg levothyroxine or placebo, taken from conception to the end of pregnancy.
The rate of pregnancy was similar in the levothyroxine and placebo groups (56.6% vs. 58.3%, respectively), as was the live birth rate (37.4% vs. 37.9%), despite the observation that the levothyroxine group had consistently lower serum thyrotropin and higher free T4 concentrations than did the placebo group.
There were also no significant differences between the two groups in secondary outcomes of miscarriage, preterm birth, or neonatal outcomes such as birth weight.
Researchers also saw no statistically significant differences in the rate of serious adverse events or in the number of women who showed abnormal results on thyroid function tests.
The authors noted that the dosage of levothyroxine used in the study was fixed, leaving the possibility that “the dose may need to be adjusted depending on the participant’s body weight, thyroid peroxidase antibody level, or thyrotropin concentration.”
Existing guidelines from the American Thyroid Association acknowledge the lack of evidence in favor of levothyroxine decreasing the risk of pregnancy loss. However, the guidelines also state that it can be considered in antibody-positive, euthyroid women with a history of loss, “given its potential benefits in comparison with its minimal risk.”
The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
SOURCE: Dhillon-Smith R et al. N Engl J Med. 2019 March 23. doi: 10.1056/NEJMoa1812537
Treatment with levothyroxine does not improve the live birth rate in women with thyroid peroxidase antibodies before conception, according to data presented at the annual meeting of the Endocrine Society.
Until now, the evidence for the use of levothyroxine in pregnant women with thyroid peroxidase antibodies but normal thyroid function has been inconclusive, Rima K. Dhillon-Smith, MBChB, PhD, of the University of Birmingham (England), and her coauthors said in a paper published simultaneously with the meeting presentation March 23 in the New England Journal of Medicine.
Previous studies have shown that women with thyroid peroxidase antibodies but normal thyroid function have a nearly fourfold higher risk of miscarriage and twofold higher risk of preterm birth, compared with women who don’t have the antibodies.
In the new double-blind study, 952 women with thyroid peroxidase antibodies, normal thyroid function, and a history of miscarriage or infertility were randomized either to daily 50 mcg levothyroxine or placebo, taken from conception to the end of pregnancy.
The rate of pregnancy was similar in the levothyroxine and placebo groups (56.6% vs. 58.3%, respectively), as was the live birth rate (37.4% vs. 37.9%), despite the observation that the levothyroxine group had consistently lower serum thyrotropin and higher free T4 concentrations than did the placebo group.
There were also no significant differences between the two groups in secondary outcomes of miscarriage, preterm birth, or neonatal outcomes such as birth weight.
Researchers also saw no statistically significant differences in the rate of serious adverse events or in the number of women who showed abnormal results on thyroid function tests.
The authors noted that the dosage of levothyroxine used in the study was fixed, leaving the possibility that “the dose may need to be adjusted depending on the participant’s body weight, thyroid peroxidase antibody level, or thyrotropin concentration.”
Existing guidelines from the American Thyroid Association acknowledge the lack of evidence in favor of levothyroxine decreasing the risk of pregnancy loss. However, the guidelines also state that it can be considered in antibody-positive, euthyroid women with a history of loss, “given its potential benefits in comparison with its minimal risk.”
The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
SOURCE: Dhillon-Smith R et al. N Engl J Med. 2019 March 23. doi: 10.1056/NEJMoa1812537
FROM ENDO 2019
Key clinical point:
Major finding: Pregnancy rates and outcomes were similar in women treated with levothyroxine and those treated with placebo.
Study details: Double-blind, randomized, placebo-controlled trial in 952 women.
Disclosures: The study was supported by the National Institute for Health Research. No conflicts of interest were declared.
Source: Dhillon-Smith R et al. N Engl J Med. 2019 March 23. doi: 10.1056/NEJMoa1812537