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Among community-dwelling adults aged 65 years and older with sleep-disordered breathing, Alzheimer’s-associated brain changes may occur in the absence of cognitive impairment, investigators have found.

Among 127 adults enrolled in a randomized clinical trial of interventions to promote mental well-being in older adults, those with sleep-disordered breathing had significantly greater amyloid burden and gray-matter volume, as well as increased perfusion and metabolism in parietal-occipital regions, reported Claire André, PhD, from the French Institute of Health and Medical Research (INSERM) unit in Caen, and colleagues.

“Our findings highlight the need to treat sleep disorders in the older population, even in the absence of cognitive or behavioral manifestations,” they wrote in a study published in JAMA Neurology.

Previous studies of the possible association between sleep-disordered breathing and dementia risk have shown conflicting or inconsistent results, the authors noted.

“These discrepancies may be explained by the characteristics of patients with sleep-disordered breathing (e.g., recruited from sleep clinics versus from the community, differences in age and disease duration), the scoring criteria of respiratory events, sample sizes, or the lack of controls for possibly biasing covariates,” they wrote.

To see whether they could clear up the confusion, the investigators conducted a retrospective analysis of 127 patients who were enrolled in the Age-Well randomized, controlled trial of the Medit-Ageing European project. The participants were community-dwelling adults (mean age, 69.1 years; 63% women), who were enrolled in the trial and underwent evaluation from 2016 to 2018 at the Cyceron Cancer Center in Caen.

The participants, all of whom were cognitively unimpaired at baseline, underwent neuropsychological assessment, polysomnography, MRI, plus florbetapir- and fluorodeoxyglucose-labeled PET.

The investigators defined sleep-disordered breathing as 15 apnea-hypopnea index events per hour or higher, and compared results between those with sleep-disordered breathing and those without for each imaging modality.

Participants with sleep-disordered breathing has significantly greater amyloid burden (P = .04), gray-matter volume (P = .04), perfusion (P = .04), and metabolism (P = .001), primarily overlapping the posterior cingulate cortex and precuneus, areas known to be significantly involved in Alzheimer’s disease.

When the investigators looked for behavioral and cognitive correlates of sleep-disordered breathing severity with associated brain changes, however, they found no associations with either cognitive performance, self-reported cognitive or sleep difficulties, or symptoms of daytime sleepiness.

“Importantly, to the best of our knowledge, our results show in vivo for the first time that greater amyloid burden colocalizes with greater gray-matter volume, perfusion, and metabolism in older participants with sleep-disordered breathing who are cognitively unimpaired. We believe that these overlapping patterns reinforce the likelihood of common underlying mechanisms,” they wrote.

The Age-Well randomized clinical trial is part of the Medit-Ageing project and is funded through the European Union’s Horizon 2020 Research and Innovation Program, INSERM, and Fondation d’ Entreprise MMA des Entrepreneurs du Futur. Dr. André reported no conflicts of interest to disclose.

SOURCE: André C et al. JAMA Neurol. 2020 Mar 23. doi: 10.1001/jamaneurol.2020.0311.

Among community-dwelling adults aged 65 years and older with sleep-disordered breathing, Alzheimer’s-associated brain changes may occur in the absence of cognitive impairment, investigators have found.

Among 127 adults enrolled in a randomized clinical trial of interventions to promote mental well-being in older adults, those with sleep-disordered breathing had significantly greater amyloid burden and gray-matter volume, as well as increased perfusion and metabolism in parietal-occipital regions, reported Claire André, PhD, from the French Institute of Health and Medical Research (INSERM) unit in Caen, and colleagues.

“Our findings highlight the need to treat sleep disorders in the older population, even in the absence of cognitive or behavioral manifestations,” they wrote in a study published in JAMA Neurology.

Previous studies of the possible association between sleep-disordered breathing and dementia risk have shown conflicting or inconsistent results, the authors noted.

“These discrepancies may be explained by the characteristics of patients with sleep-disordered breathing (e.g., recruited from sleep clinics versus from the community, differences in age and disease duration), the scoring criteria of respiratory events, sample sizes, or the lack of controls for possibly biasing covariates,” they wrote.

To see whether they could clear up the confusion, the investigators conducted a retrospective analysis of 127 patients who were enrolled in the Age-Well randomized, controlled trial of the Medit-Ageing European project. The participants were community-dwelling adults (mean age, 69.1 years; 63% women), who were enrolled in the trial and underwent evaluation from 2016 to 2018 at the Cyceron Cancer Center in Caen.

The participants, all of whom were cognitively unimpaired at baseline, underwent neuropsychological assessment, polysomnography, MRI, plus florbetapir- and fluorodeoxyglucose-labeled PET.

The investigators defined sleep-disordered breathing as 15 apnea-hypopnea index events per hour or higher, and compared results between those with sleep-disordered breathing and those without for each imaging modality.

Participants with sleep-disordered breathing has significantly greater amyloid burden (P = .04), gray-matter volume (P = .04), perfusion (P = .04), and metabolism (P = .001), primarily overlapping the posterior cingulate cortex and precuneus, areas known to be significantly involved in Alzheimer’s disease.

When the investigators looked for behavioral and cognitive correlates of sleep-disordered breathing severity with associated brain changes, however, they found no associations with either cognitive performance, self-reported cognitive or sleep difficulties, or symptoms of daytime sleepiness.

“Importantly, to the best of our knowledge, our results show in vivo for the first time that greater amyloid burden colocalizes with greater gray-matter volume, perfusion, and metabolism in older participants with sleep-disordered breathing who are cognitively unimpaired. We believe that these overlapping patterns reinforce the likelihood of common underlying mechanisms,” they wrote.

The Age-Well randomized clinical trial is part of the Medit-Ageing project and is funded through the European Union’s Horizon 2020 Research and Innovation Program, INSERM, and Fondation d’ Entreprise MMA des Entrepreneurs du Futur. Dr. André reported no conflicts of interest to disclose.

SOURCE: André C et al. JAMA Neurol. 2020 Mar 23. doi: 10.1001/jamaneurol.2020.0311.

Among community-dwelling adults aged 65 years and older with sleep-disordered breathing, Alzheimer’s-associated brain changes may occur in the absence of cognitive impairment, investigators have found.

Among 127 adults enrolled in a randomized clinical trial of interventions to promote mental well-being in older adults, those with sleep-disordered breathing had significantly greater amyloid burden and gray-matter volume, as well as increased perfusion and metabolism in parietal-occipital regions, reported Claire André, PhD, from the French Institute of Health and Medical Research (INSERM) unit in Caen, and colleagues.

“Our findings highlight the need to treat sleep disorders in the older population, even in the absence of cognitive or behavioral manifestations,” they wrote in a study published in JAMA Neurology.

Previous studies of the possible association between sleep-disordered breathing and dementia risk have shown conflicting or inconsistent results, the authors noted.

“These discrepancies may be explained by the characteristics of patients with sleep-disordered breathing (e.g., recruited from sleep clinics versus from the community, differences in age and disease duration), the scoring criteria of respiratory events, sample sizes, or the lack of controls for possibly biasing covariates,” they wrote.

To see whether they could clear up the confusion, the investigators conducted a retrospective analysis of 127 patients who were enrolled in the Age-Well randomized, controlled trial of the Medit-Ageing European project. The participants were community-dwelling adults (mean age, 69.1 years; 63% women), who were enrolled in the trial and underwent evaluation from 2016 to 2018 at the Cyceron Cancer Center in Caen.

The participants, all of whom were cognitively unimpaired at baseline, underwent neuropsychological assessment, polysomnography, MRI, plus florbetapir- and fluorodeoxyglucose-labeled PET.

The investigators defined sleep-disordered breathing as 15 apnea-hypopnea index events per hour or higher, and compared results between those with sleep-disordered breathing and those without for each imaging modality.

Participants with sleep-disordered breathing has significantly greater amyloid burden (P = .04), gray-matter volume (P = .04), perfusion (P = .04), and metabolism (P = .001), primarily overlapping the posterior cingulate cortex and precuneus, areas known to be significantly involved in Alzheimer’s disease.

When the investigators looked for behavioral and cognitive correlates of sleep-disordered breathing severity with associated brain changes, however, they found no associations with either cognitive performance, self-reported cognitive or sleep difficulties, or symptoms of daytime sleepiness.

“Importantly, to the best of our knowledge, our results show in vivo for the first time that greater amyloid burden colocalizes with greater gray-matter volume, perfusion, and metabolism in older participants with sleep-disordered breathing who are cognitively unimpaired. We believe that these overlapping patterns reinforce the likelihood of common underlying mechanisms,” they wrote.

The Age-Well randomized clinical trial is part of the Medit-Ageing project and is funded through the European Union’s Horizon 2020 Research and Innovation Program, INSERM, and Fondation d’ Entreprise MMA des Entrepreneurs du Futur. Dr. André reported no conflicts of interest to disclose.

SOURCE: André C et al. JAMA Neurol. 2020 Mar 23. doi: 10.1001/jamaneurol.2020.0311.

Two months after the first patient with COVID-19 was identified in China, the first case was reported in the United States in the Seattle, Washington, metropolitan area.

Seattle rapidly became the first US epicenter for COVID-19, and local experts are now offering their expertise and advice on how to provide optimal cancer care during the pandemic in a special feature published online March 20 in the Journal of the National Comprehensive Cancer Network.

“We began implementing measures in early March, including infection control and screening of visitors, staff, and patients at the door,” said lead author Masumi Ueda, MD, who holds positions at the Seattle Cancer Care Alliance, the University of Washington, and the Fred Hutchinson Research Center.

“A lot of changes have been implemented, and it changes on a daily basis. We are responding to the growing rate of COVID-19 infection in the community,” she told Medscape Medical News.

Ueda notes that as a result of the quick implementation of new procedures, so far, very few cancer patients at their facilities have been infected by the virus. “It has not hit our cancer population hard, which is a good thing,” she said.

Create “Incident Command Structure”

In sharing their experience, the authors emphasize the importance of keeping channels of communication open between all stakeholders ― administrators and staff, patients, caregivers, and the general public. They also recommend that each facility create an “incident command structure” that can provide early coordination of institution-wide efforts and that can rapidly respond to changing information.

Ueda noted that their command structure was set up very early on, “so we could get communication set up and start building an infrastructure for response.”

Several areas of care that required new strategies were addressed, both to protect patients and to work around staff shortages caused by possible exposure and/or school closings, as well as projected shortages of supplies and hospital resources.

First and foremost was to identify patients and visitors who had respiratory symptoms and to provide them with masks. Although this is always routine practice during the respiratory virus season, screening has now been initiated at entry points throughout the system.

“We were lucky in Seattle and Washington state in that the University of Washington virology lab developed PCR [polymerase chain reaction] testing early on for COVID-19, which subsequently got FDA approval,” said Ueda. “So we were able to have local testing and didn’t have to rely on the state lab. Testing has also been rapidly scaled up.”

Initiating a comprehensive policy for testing staff, tracking results and exposures for persons under investigation, and defining when it is possible to return to work are essential elements for maintaining a stable workforce. In addition, reinforcing a strict “stay at home when ill” policy and providing access to testing for symptomatic staff have been key to limiting exposures.

“What is unique to our region is that we had testing early on, and we are turning it around in 24 hours,” she pointed out. “This is important for staff to be able to return to work.” Currently, staff, patients, and visitors are being tested only if they show the cardinal symptoms associated with COVID-19: fever, shortness of breath, and cough, although muscle aches have recently been added to their testing protocol.

“I think if we had unlimited capacity, we might consider testing people who are asymptomatic,” Ueda noted, “although if you don’t have symptoms, you may not have the viral load needed for an accurate test.”

Educational materials explaining infection control were also needed for patients and families, along with signs and a website to provide COVID-19 education. These were quickly developed.

In addition, a telephone triage line was established for patients with mild symptoms in order to minimize exposures in clinics and to lessen the number of patients presenting at emergency departments.

Outpatient Care

Because theirs is a referral center, many cancer patients come from out of town, and so there is concern about exposing nonlocal patients to COVID-19 as the virus spreads in the Seattle area. In addition, staffing shortages due to factors such as illness, exposure, and school closures are anticipated.

To address these problems, an initial priority was to establish a “multilayer” coverage system for the clinics in the event that practitioners had to be quarantined on short notice, the authors explain.

One decision was to reschedule all wellness visits for current patients or to use telemedicine. Capacity for that option expanded quickly, which was greatly helped by the recent decision by the Centers for Medicare & Medicaid Services to lift Medicare restrictions on the use of certain telemedicine services.

Another approach is to defer all consultations for second opinions for patients who were already undergoing treatment and to increase clinic hours of operations and capabilities for acute evaluations. This helps reserve emergency departments and hospital resources for patients who require higher-level care, the authors comment.

Treatment Decisions

Treatment decisions were more challenging to make, the authors note. One decision was that, despite the risk for COVID-19 for patients with solid tumors, adjuvant therapy with curative intent should proceed, they note. Similarly, patients with metastatic disease might lose the window of opportunity for treatment if it is delayed.

Treatment for aggressive hematologic malignancies is usually urgent, and stem cell transplant and cellular immunotherapies that provide curative treatments cannot be delayed in many cases.

Enrollment in clinical trials will most likely be limited to those trials that are most likely to benefit the patient.

Ueda noted that, because their patients come from all over the country, they are now conducting consultations for stem cell transplant by telephone so that nonlocal patients do not have to travel to Seattle. “If there is some way we can delay the treatment, we have taken that approach,” Ueda told Medscape Medical News. “If we can divert a patient to an area that is not as heavily affected, that’s another option we are taking.”

Although cancer surgery is not considered elective, surgical intervention needs to be prioritized, the authors comment. In the Seattle system, there is currently a 2-week ban on elective surgery in the healthcare system, owing to limited availability of personal protective equipment (PPE), staffing, and beds.

The oncology teams are currently reviewing treatment regimens to determine which treatments might lessen immunosuppression and which treatment options can be moved from the inpatient to the outpatient setting or can be delayed.

Inpatient Care

For hospitalized patients, several issues are being addressed. The priority is to prepare for an upcoming shortage of beds and resources because of the surge of patients with COVID-19 that is predicted. For both clinic and hospitalized patients, shortages of blood products have necessitated stricter adherence to thresholds for transfusion, and consideration is being given to lowering those thresholds.

Another important problem is the need to conserve PPE, which includes masks, gowns, gloves, and other products. The Seattle teams have implemented solutions such as favoring handwashing with soap and water over the use of hand gel for standard-precaution rooms, limiting the number of personnel entering patient rooms (so as to use less PPE), and reducing nursing procedures that require PPE, such as measuring urine output, unless they are necessary.

In addition, a no-visitor policy has been adopted in inpatient units to conserve PPE, with the exception of end-of-life situations.

The Future

The future trajectory of the COVID-19 pandemic is uncertain, Ueda commented. She emphasized that “we must continue to prepare for its widespread impact. The unknown is what we are looking at. We are expecting it to evolve, and the number of infections cannot go down.”

Ueda and coauthors end their article on a positive note. “To many of us, this has become the health care challenge of our generation, one that modern cancer therapy has never had to face. We will prevail, and when the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity.”

Two months after the first patient with COVID-19 was identified in China, the first case was reported in the United States in the Seattle, Washington, metropolitan area.

Seattle rapidly became the first US epicenter for COVID-19, and local experts are now offering their expertise and advice on how to provide optimal cancer care during the pandemic in a special feature published online March 20 in the Journal of the National Comprehensive Cancer Network.

“We began implementing measures in early March, including infection control and screening of visitors, staff, and patients at the door,” said lead author Masumi Ueda, MD, who holds positions at the Seattle Cancer Care Alliance, the University of Washington, and the Fred Hutchinson Research Center.

“A lot of changes have been implemented, and it changes on a daily basis. We are responding to the growing rate of COVID-19 infection in the community,” she told Medscape Medical News.

Ueda notes that as a result of the quick implementation of new procedures, so far, very few cancer patients at their facilities have been infected by the virus. “It has not hit our cancer population hard, which is a good thing,” she said.

Create “Incident Command Structure”

In sharing their experience, the authors emphasize the importance of keeping channels of communication open between all stakeholders ― administrators and staff, patients, caregivers, and the general public. They also recommend that each facility create an “incident command structure” that can provide early coordination of institution-wide efforts and that can rapidly respond to changing information.

Ueda noted that their command structure was set up very early on, “so we could get communication set up and start building an infrastructure for response.”

Several areas of care that required new strategies were addressed, both to protect patients and to work around staff shortages caused by possible exposure and/or school closings, as well as projected shortages of supplies and hospital resources.

First and foremost was to identify patients and visitors who had respiratory symptoms and to provide them with masks. Although this is always routine practice during the respiratory virus season, screening has now been initiated at entry points throughout the system.

“We were lucky in Seattle and Washington state in that the University of Washington virology lab developed PCR [polymerase chain reaction] testing early on for COVID-19, which subsequently got FDA approval,” said Ueda. “So we were able to have local testing and didn’t have to rely on the state lab. Testing has also been rapidly scaled up.”

Initiating a comprehensive policy for testing staff, tracking results and exposures for persons under investigation, and defining when it is possible to return to work are essential elements for maintaining a stable workforce. In addition, reinforcing a strict “stay at home when ill” policy and providing access to testing for symptomatic staff have been key to limiting exposures.

“What is unique to our region is that we had testing early on, and we are turning it around in 24 hours,” she pointed out. “This is important for staff to be able to return to work.” Currently, staff, patients, and visitors are being tested only if they show the cardinal symptoms associated with COVID-19: fever, shortness of breath, and cough, although muscle aches have recently been added to their testing protocol.

“I think if we had unlimited capacity, we might consider testing people who are asymptomatic,” Ueda noted, “although if you don’t have symptoms, you may not have the viral load needed for an accurate test.”

Educational materials explaining infection control were also needed for patients and families, along with signs and a website to provide COVID-19 education. These were quickly developed.

In addition, a telephone triage line was established for patients with mild symptoms in order to minimize exposures in clinics and to lessen the number of patients presenting at emergency departments.

Outpatient Care

Because theirs is a referral center, many cancer patients come from out of town, and so there is concern about exposing nonlocal patients to COVID-19 as the virus spreads in the Seattle area. In addition, staffing shortages due to factors such as illness, exposure, and school closures are anticipated.

To address these problems, an initial priority was to establish a “multilayer” coverage system for the clinics in the event that practitioners had to be quarantined on short notice, the authors explain.

One decision was to reschedule all wellness visits for current patients or to use telemedicine. Capacity for that option expanded quickly, which was greatly helped by the recent decision by the Centers for Medicare & Medicaid Services to lift Medicare restrictions on the use of certain telemedicine services.

Another approach is to defer all consultations for second opinions for patients who were already undergoing treatment and to increase clinic hours of operations and capabilities for acute evaluations. This helps reserve emergency departments and hospital resources for patients who require higher-level care, the authors comment.

Treatment Decisions

Treatment decisions were more challenging to make, the authors note. One decision was that, despite the risk for COVID-19 for patients with solid tumors, adjuvant therapy with curative intent should proceed, they note. Similarly, patients with metastatic disease might lose the window of opportunity for treatment if it is delayed.

Treatment for aggressive hematologic malignancies is usually urgent, and stem cell transplant and cellular immunotherapies that provide curative treatments cannot be delayed in many cases.

Enrollment in clinical trials will most likely be limited to those trials that are most likely to benefit the patient.

Ueda noted that, because their patients come from all over the country, they are now conducting consultations for stem cell transplant by telephone so that nonlocal patients do not have to travel to Seattle. “If there is some way we can delay the treatment, we have taken that approach,” Ueda told Medscape Medical News. “If we can divert a patient to an area that is not as heavily affected, that’s another option we are taking.”

Although cancer surgery is not considered elective, surgical intervention needs to be prioritized, the authors comment. In the Seattle system, there is currently a 2-week ban on elective surgery in the healthcare system, owing to limited availability of personal protective equipment (PPE), staffing, and beds.

The oncology teams are currently reviewing treatment regimens to determine which treatments might lessen immunosuppression and which treatment options can be moved from the inpatient to the outpatient setting or can be delayed.

Inpatient Care

For hospitalized patients, several issues are being addressed. The priority is to prepare for an upcoming shortage of beds and resources because of the surge of patients with COVID-19 that is predicted. For both clinic and hospitalized patients, shortages of blood products have necessitated stricter adherence to thresholds for transfusion, and consideration is being given to lowering those thresholds.

Another important problem is the need to conserve PPE, which includes masks, gowns, gloves, and other products. The Seattle teams have implemented solutions such as favoring handwashing with soap and water over the use of hand gel for standard-precaution rooms, limiting the number of personnel entering patient rooms (so as to use less PPE), and reducing nursing procedures that require PPE, such as measuring urine output, unless they are necessary.

In addition, a no-visitor policy has been adopted in inpatient units to conserve PPE, with the exception of end-of-life situations.

The Future

The future trajectory of the COVID-19 pandemic is uncertain, Ueda commented. She emphasized that “we must continue to prepare for its widespread impact. The unknown is what we are looking at. We are expecting it to evolve, and the number of infections cannot go down.”

Ueda and coauthors end their article on a positive note. “To many of us, this has become the health care challenge of our generation, one that modern cancer therapy has never had to face. We will prevail, and when the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity.”

Two months after the first patient with COVID-19 was identified in China, the first case was reported in the United States in the Seattle, Washington, metropolitan area.

Seattle rapidly became the first US epicenter for COVID-19, and local experts are now offering their expertise and advice on how to provide optimal cancer care during the pandemic in a special feature published online March 20 in the Journal of the National Comprehensive Cancer Network.

“We began implementing measures in early March, including infection control and screening of visitors, staff, and patients at the door,” said lead author Masumi Ueda, MD, who holds positions at the Seattle Cancer Care Alliance, the University of Washington, and the Fred Hutchinson Research Center.

“A lot of changes have been implemented, and it changes on a daily basis. We are responding to the growing rate of COVID-19 infection in the community,” she told Medscape Medical News.

Ueda notes that as a result of the quick implementation of new procedures, so far, very few cancer patients at their facilities have been infected by the virus. “It has not hit our cancer population hard, which is a good thing,” she said.

Create “Incident Command Structure”

In sharing their experience, the authors emphasize the importance of keeping channels of communication open between all stakeholders ― administrators and staff, patients, caregivers, and the general public. They also recommend that each facility create an “incident command structure” that can provide early coordination of institution-wide efforts and that can rapidly respond to changing information.

Ueda noted that their command structure was set up very early on, “so we could get communication set up and start building an infrastructure for response.”

Several areas of care that required new strategies were addressed, both to protect patients and to work around staff shortages caused by possible exposure and/or school closings, as well as projected shortages of supplies and hospital resources.

First and foremost was to identify patients and visitors who had respiratory symptoms and to provide them with masks. Although this is always routine practice during the respiratory virus season, screening has now been initiated at entry points throughout the system.

“We were lucky in Seattle and Washington state in that the University of Washington virology lab developed PCR [polymerase chain reaction] testing early on for COVID-19, which subsequently got FDA approval,” said Ueda. “So we were able to have local testing and didn’t have to rely on the state lab. Testing has also been rapidly scaled up.”

Initiating a comprehensive policy for testing staff, tracking results and exposures for persons under investigation, and defining when it is possible to return to work are essential elements for maintaining a stable workforce. In addition, reinforcing a strict “stay at home when ill” policy and providing access to testing for symptomatic staff have been key to limiting exposures.

“What is unique to our region is that we had testing early on, and we are turning it around in 24 hours,” she pointed out. “This is important for staff to be able to return to work.” Currently, staff, patients, and visitors are being tested only if they show the cardinal symptoms associated with COVID-19: fever, shortness of breath, and cough, although muscle aches have recently been added to their testing protocol.

“I think if we had unlimited capacity, we might consider testing people who are asymptomatic,” Ueda noted, “although if you don’t have symptoms, you may not have the viral load needed for an accurate test.”

Educational materials explaining infection control were also needed for patients and families, along with signs and a website to provide COVID-19 education. These were quickly developed.

In addition, a telephone triage line was established for patients with mild symptoms in order to minimize exposures in clinics and to lessen the number of patients presenting at emergency departments.

Outpatient Care

Because theirs is a referral center, many cancer patients come from out of town, and so there is concern about exposing nonlocal patients to COVID-19 as the virus spreads in the Seattle area. In addition, staffing shortages due to factors such as illness, exposure, and school closures are anticipated.

To address these problems, an initial priority was to establish a “multilayer” coverage system for the clinics in the event that practitioners had to be quarantined on short notice, the authors explain.

One decision was to reschedule all wellness visits for current patients or to use telemedicine. Capacity for that option expanded quickly, which was greatly helped by the recent decision by the Centers for Medicare & Medicaid Services to lift Medicare restrictions on the use of certain telemedicine services.

Another approach is to defer all consultations for second opinions for patients who were already undergoing treatment and to increase clinic hours of operations and capabilities for acute evaluations. This helps reserve emergency departments and hospital resources for patients who require higher-level care, the authors comment.

Treatment Decisions

Treatment decisions were more challenging to make, the authors note. One decision was that, despite the risk for COVID-19 for patients with solid tumors, adjuvant therapy with curative intent should proceed, they note. Similarly, patients with metastatic disease might lose the window of opportunity for treatment if it is delayed.

Treatment for aggressive hematologic malignancies is usually urgent, and stem cell transplant and cellular immunotherapies that provide curative treatments cannot be delayed in many cases.

Enrollment in clinical trials will most likely be limited to those trials that are most likely to benefit the patient.

Ueda noted that, because their patients come from all over the country, they are now conducting consultations for stem cell transplant by telephone so that nonlocal patients do not have to travel to Seattle. “If there is some way we can delay the treatment, we have taken that approach,” Ueda told Medscape Medical News. “If we can divert a patient to an area that is not as heavily affected, that’s another option we are taking.”

Although cancer surgery is not considered elective, surgical intervention needs to be prioritized, the authors comment. In the Seattle system, there is currently a 2-week ban on elective surgery in the healthcare system, owing to limited availability of personal protective equipment (PPE), staffing, and beds.

The oncology teams are currently reviewing treatment regimens to determine which treatments might lessen immunosuppression and which treatment options can be moved from the inpatient to the outpatient setting or can be delayed.

Inpatient Care

For hospitalized patients, several issues are being addressed. The priority is to prepare for an upcoming shortage of beds and resources because of the surge of patients with COVID-19 that is predicted. For both clinic and hospitalized patients, shortages of blood products have necessitated stricter adherence to thresholds for transfusion, and consideration is being given to lowering those thresholds.

Another important problem is the need to conserve PPE, which includes masks, gowns, gloves, and other products. The Seattle teams have implemented solutions such as favoring handwashing with soap and water over the use of hand gel for standard-precaution rooms, limiting the number of personnel entering patient rooms (so as to use less PPE), and reducing nursing procedures that require PPE, such as measuring urine output, unless they are necessary.

In addition, a no-visitor policy has been adopted in inpatient units to conserve PPE, with the exception of end-of-life situations.

The Future

The future trajectory of the COVID-19 pandemic is uncertain, Ueda commented. She emphasized that “we must continue to prepare for its widespread impact. The unknown is what we are looking at. We are expecting it to evolve, and the number of infections cannot go down.”

Ueda and coauthors end their article on a positive note. “To many of us, this has become the health care challenge of our generation, one that modern cancer therapy has never had to face. We will prevail, and when the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity.”

As the coronavirus pandemic escalates in the United States, Medscape Oncology reached out to a group of our contributors and asked them to provide their perspective on how their oncology departments and centers are preparing. Here are their responses to a number of issues facing oncologists in the US and around the world.
 

Have you shifted nonurgent follow-up visits to telemedicine, either via video or phone?

Kathy Miller, MD, Associate Director of Indiana University Simon Cancer Center: We are reviewing our clinic schedules and identifying “routine” follow-up patients who can be rescheduled. When patients are contacted to reschedule, they are asked if they have any urgent, immediate concerns that need to be addressed before the new appointment. If yes, they are offered a virtual visit.

Don Dizon, MD, Director of Women’s Cancers, Lifespan Cancer Institute; Director of Medical Oncology, Rhode Island Hospital: We have started to do this in preparation for a surge of people with COVID-19. Patients who are in long-term follow-up (no evidence of disease at 3 years or longer, being seen annually) or those in routine surveillance after curative treatment (that is, seen every 3 months) as well as those being seen for supportive care–type visits, like sexual health or survivorship, are all being contacted and visits are being moved to telehealth.

Jeffrey S. Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center: Yes. Any follow-up, nontreatment visits are done by phone or video if the patient agrees. (They all have).
 

Have you delayed or canceled cancer surgeries?

Ravi B. Parikh, MD, MPP, Medical oncologist at the University of Pennsylvania and the Philadelphia VA Medical Center: The University of Pennsylvania has taken this seriously. We’ve canceled all elective surgeries, have ramped up our telemedicine (video and phone) capabilities significantly, are limiting our appointments mostly to on-treatment visits, and have been asked to reconsider regular scans and reviews.

Dizon: We have not done this. There are apparently differences in interpretation in what institutions might mean as “elective surgeries.” At our institution, surgery for invasive malignancies is not elective. However, this may (or will) change if resources become an issue.

Lidia Schapira, MD, Associate Professor of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute: Delaying elective surgery is something that hospitals here have already implemented, and I imagine that this trend will spread. But it may be difficult to decide in situations that are not exactly “life-saving” but where an earlier intervention could preserve function or improve quality of life.

Mark A. Lewis, MD, Director of Gastrointestinal Oncology at Intermountain Healthcare in Utah: Cancer surgeries have not been deemed elective or delayed.

Have you delayed or altered the delivery of potentially immune-comprising treatments?

David Kerr, MD, Professor of Cancer Medicine at the University of Oxford in England: We are considering delaying initiation of our adjuvant colorectal cancer treatments, as we have data from our own QUASAR trials suggesting that patients who commence chemotherapy between 2 and 6 weeks do equally as well as those who begin 6-12 weeks after surgery.

Parikh: I personally haven’t delayed giving chemotherapy to avoid immune compromise, but I believe some others may have. It’s a delicate balance between wanting to ensure cancer control and making sure we are flattening the curve. As an example, though, I delayed three on-treatment visits for my clinic last Monday, and I converted 70% of my visits to telemedicine. However, I’m a genitourinary cancer specialist and the treatments I give are very different from others.

Lewis: The most difficult calculus is around adjuvant therapy. For metastatic patients, I am trying to use the least immunosuppressive regimen possible that will still control their disease. As you can imagine, it’s an assessment of competing risks.

Schapira: Patients who need essential anticancer therapy should still get it, but attempts to deintensify therapy should continue—for example, holding or postponing treatment without harm (based on evidence, not opinion). This may be possible for patients considering hormonal therapies for breast or prostate cancer.

Patients who need radiation should discuss the timing with their radiation oncologist. In some cases, it may be possible to delay treatment without affecting outcomes, but these decisions should be made carefully. Alternatively, shorter courses of radiation may be appropriate.
 

Have you advised your own patients differently given the high risk to cancer patients?

Kerr: We have factored potential infection with the virus into discussions where the benefits of chemotherapy are very marginal. This could tip the balance toward the patient deciding not to pursue chemotherapy.

Dizon: The data from China are not entirely crystal-clear. While they noted that people with active cancer and those who had a history of cancer are at increased risk for more severe infections and worse outcomes, the Chinese cohort was small, and compared with people without cancer, it tended to be much older and to be smokers (former or current). Having said this, we are counseling everyone about the importance of social distancing, washing hands, and not touching your face.

Lewis: If I have a complete blood count with a differential that includes lymphocytes, I can advise my lymphopenic patients (who are particularly vulnerable to viral infection) to take special precautions regarding social distancing in their own families.
 

Have any of your hospitalized patients been affected by policy changes to prepare beds/departments for the expected increase in COVID-19–positive patients?

Weber: Not yet.

Dizon: No, not at the moment.
 

Have you been asked to assist with other services or COVID-19 task forces?

Dizon: I am keenly involved in the preparations and modifications to procedures, including staffing decisions in outpatient, movement to telehealth, and work-from-home policies.

Lewis: I am engaged in system-wide COVID-19 efforts around oncology.

Kerr: Perhaps oddest of all, I am learning with some of our junior doctors to care for ventilated patients. I still consider myself enough of a general physician that I would hope to be able to contribute to the truly sick, but I accept that I do need an appropriate refresher course.

Bishal Gyawali, MD, PhD, medical oncologist at Queen’s University Cancer Research Institute: Queen’s Hospital medical students are now volunteering to help with daycare, groceries, and other tasks for staff who are working in the hospital.
 

Are you experiencing any shortages in personal protective equipment (PPE) at your center?

Miller: Some supplies are running short, though none are frankly out at this point. However, rationing and controls are in place to stretch the supplies as far as possible, including reusing some PPE.

Dizon: We are rationing face masks and N95 respirators, eye shields, and even surgical scrubs. We are talking about postponing elective surgery to save PPE but are not yet to that point. We’re asking that face masks be reused for at least 2 days, maybe longer. PPEs are one per day. Scrubs are kept secure.

Lewis: We are being very careful not to overuse PPE but currently have an adequate inventory. We have had to move gloves and masks to areas where they are not accessible to the general public, as otherwise they were being stolen (this started weeks ago).

Kerr: Our National Health System has an adequate supply of PPE equipment centrally, but there seems to be a problem with distribution, as some hospitals are reporting shortages.

Weber: Masks are in short supply, so they are being used for several days if not wet. We are short of plastic gowns and are using paper chemo gowns. Similar story at many places.

This article first appeared on Medscape.com.

As the coronavirus pandemic escalates in the United States, Medscape Oncology reached out to a group of our contributors and asked them to provide their perspective on how their oncology departments and centers are preparing. Here are their responses to a number of issues facing oncologists in the US and around the world.
 

Have you shifted nonurgent follow-up visits to telemedicine, either via video or phone?

Kathy Miller, MD, Associate Director of Indiana University Simon Cancer Center: We are reviewing our clinic schedules and identifying “routine” follow-up patients who can be rescheduled. When patients are contacted to reschedule, they are asked if they have any urgent, immediate concerns that need to be addressed before the new appointment. If yes, they are offered a virtual visit.

Don Dizon, MD, Director of Women’s Cancers, Lifespan Cancer Institute; Director of Medical Oncology, Rhode Island Hospital: We have started to do this in preparation for a surge of people with COVID-19. Patients who are in long-term follow-up (no evidence of disease at 3 years or longer, being seen annually) or those in routine surveillance after curative treatment (that is, seen every 3 months) as well as those being seen for supportive care–type visits, like sexual health or survivorship, are all being contacted and visits are being moved to telehealth.

Jeffrey S. Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center: Yes. Any follow-up, nontreatment visits are done by phone or video if the patient agrees. (They all have).
 

Have you delayed or canceled cancer surgeries?

Ravi B. Parikh, MD, MPP, Medical oncologist at the University of Pennsylvania and the Philadelphia VA Medical Center: The University of Pennsylvania has taken this seriously. We’ve canceled all elective surgeries, have ramped up our telemedicine (video and phone) capabilities significantly, are limiting our appointments mostly to on-treatment visits, and have been asked to reconsider regular scans and reviews.

Dizon: We have not done this. There are apparently differences in interpretation in what institutions might mean as “elective surgeries.” At our institution, surgery for invasive malignancies is not elective. However, this may (or will) change if resources become an issue.

Lidia Schapira, MD, Associate Professor of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute: Delaying elective surgery is something that hospitals here have already implemented, and I imagine that this trend will spread. But it may be difficult to decide in situations that are not exactly “life-saving” but where an earlier intervention could preserve function or improve quality of life.

Mark A. Lewis, MD, Director of Gastrointestinal Oncology at Intermountain Healthcare in Utah: Cancer surgeries have not been deemed elective or delayed.

Have you delayed or altered the delivery of potentially immune-comprising treatments?

David Kerr, MD, Professor of Cancer Medicine at the University of Oxford in England: We are considering delaying initiation of our adjuvant colorectal cancer treatments, as we have data from our own QUASAR trials suggesting that patients who commence chemotherapy between 2 and 6 weeks do equally as well as those who begin 6-12 weeks after surgery.

Parikh: I personally haven’t delayed giving chemotherapy to avoid immune compromise, but I believe some others may have. It’s a delicate balance between wanting to ensure cancer control and making sure we are flattening the curve. As an example, though, I delayed three on-treatment visits for my clinic last Monday, and I converted 70% of my visits to telemedicine. However, I’m a genitourinary cancer specialist and the treatments I give are very different from others.

Lewis: The most difficult calculus is around adjuvant therapy. For metastatic patients, I am trying to use the least immunosuppressive regimen possible that will still control their disease. As you can imagine, it’s an assessment of competing risks.

Schapira: Patients who need essential anticancer therapy should still get it, but attempts to deintensify therapy should continue—for example, holding or postponing treatment without harm (based on evidence, not opinion). This may be possible for patients considering hormonal therapies for breast or prostate cancer.

Patients who need radiation should discuss the timing with their radiation oncologist. In some cases, it may be possible to delay treatment without affecting outcomes, but these decisions should be made carefully. Alternatively, shorter courses of radiation may be appropriate.
 

Have you advised your own patients differently given the high risk to cancer patients?

Kerr: We have factored potential infection with the virus into discussions where the benefits of chemotherapy are very marginal. This could tip the balance toward the patient deciding not to pursue chemotherapy.

Dizon: The data from China are not entirely crystal-clear. While they noted that people with active cancer and those who had a history of cancer are at increased risk for more severe infections and worse outcomes, the Chinese cohort was small, and compared with people without cancer, it tended to be much older and to be smokers (former or current). Having said this, we are counseling everyone about the importance of social distancing, washing hands, and not touching your face.

Lewis: If I have a complete blood count with a differential that includes lymphocytes, I can advise my lymphopenic patients (who are particularly vulnerable to viral infection) to take special precautions regarding social distancing in their own families.
 

Have any of your hospitalized patients been affected by policy changes to prepare beds/departments for the expected increase in COVID-19–positive patients?

Weber: Not yet.

Dizon: No, not at the moment.
 

Have you been asked to assist with other services or COVID-19 task forces?

Dizon: I am keenly involved in the preparations and modifications to procedures, including staffing decisions in outpatient, movement to telehealth, and work-from-home policies.

Lewis: I am engaged in system-wide COVID-19 efforts around oncology.

Kerr: Perhaps oddest of all, I am learning with some of our junior doctors to care for ventilated patients. I still consider myself enough of a general physician that I would hope to be able to contribute to the truly sick, but I accept that I do need an appropriate refresher course.

Bishal Gyawali, MD, PhD, medical oncologist at Queen’s University Cancer Research Institute: Queen’s Hospital medical students are now volunteering to help with daycare, groceries, and other tasks for staff who are working in the hospital.
 

Are you experiencing any shortages in personal protective equipment (PPE) at your center?

Miller: Some supplies are running short, though none are frankly out at this point. However, rationing and controls are in place to stretch the supplies as far as possible, including reusing some PPE.

Dizon: We are rationing face masks and N95 respirators, eye shields, and even surgical scrubs. We are talking about postponing elective surgery to save PPE but are not yet to that point. We’re asking that face masks be reused for at least 2 days, maybe longer. PPEs are one per day. Scrubs are kept secure.

Lewis: We are being very careful not to overuse PPE but currently have an adequate inventory. We have had to move gloves and masks to areas where they are not accessible to the general public, as otherwise they were being stolen (this started weeks ago).

Kerr: Our National Health System has an adequate supply of PPE equipment centrally, but there seems to be a problem with distribution, as some hospitals are reporting shortages.

Weber: Masks are in short supply, so they are being used for several days if not wet. We are short of plastic gowns and are using paper chemo gowns. Similar story at many places.

This article first appeared on Medscape.com.

As the coronavirus pandemic escalates in the United States, Medscape Oncology reached out to a group of our contributors and asked them to provide their perspective on how their oncology departments and centers are preparing. Here are their responses to a number of issues facing oncologists in the US and around the world.
 

Have you shifted nonurgent follow-up visits to telemedicine, either via video or phone?

Kathy Miller, MD, Associate Director of Indiana University Simon Cancer Center: We are reviewing our clinic schedules and identifying “routine” follow-up patients who can be rescheduled. When patients are contacted to reschedule, they are asked if they have any urgent, immediate concerns that need to be addressed before the new appointment. If yes, they are offered a virtual visit.

Don Dizon, MD, Director of Women’s Cancers, Lifespan Cancer Institute; Director of Medical Oncology, Rhode Island Hospital: We have started to do this in preparation for a surge of people with COVID-19. Patients who are in long-term follow-up (no evidence of disease at 3 years or longer, being seen annually) or those in routine surveillance after curative treatment (that is, seen every 3 months) as well as those being seen for supportive care–type visits, like sexual health or survivorship, are all being contacted and visits are being moved to telehealth.

Jeffrey S. Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center: Yes. Any follow-up, nontreatment visits are done by phone or video if the patient agrees. (They all have).
 

Have you delayed or canceled cancer surgeries?

Ravi B. Parikh, MD, MPP, Medical oncologist at the University of Pennsylvania and the Philadelphia VA Medical Center: The University of Pennsylvania has taken this seriously. We’ve canceled all elective surgeries, have ramped up our telemedicine (video and phone) capabilities significantly, are limiting our appointments mostly to on-treatment visits, and have been asked to reconsider regular scans and reviews.

Dizon: We have not done this. There are apparently differences in interpretation in what institutions might mean as “elective surgeries.” At our institution, surgery for invasive malignancies is not elective. However, this may (or will) change if resources become an issue.

Lidia Schapira, MD, Associate Professor of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute: Delaying elective surgery is something that hospitals here have already implemented, and I imagine that this trend will spread. But it may be difficult to decide in situations that are not exactly “life-saving” but where an earlier intervention could preserve function or improve quality of life.

Mark A. Lewis, MD, Director of Gastrointestinal Oncology at Intermountain Healthcare in Utah: Cancer surgeries have not been deemed elective or delayed.

Have you delayed or altered the delivery of potentially immune-comprising treatments?

David Kerr, MD, Professor of Cancer Medicine at the University of Oxford in England: We are considering delaying initiation of our adjuvant colorectal cancer treatments, as we have data from our own QUASAR trials suggesting that patients who commence chemotherapy between 2 and 6 weeks do equally as well as those who begin 6-12 weeks after surgery.

Parikh: I personally haven’t delayed giving chemotherapy to avoid immune compromise, but I believe some others may have. It’s a delicate balance between wanting to ensure cancer control and making sure we are flattening the curve. As an example, though, I delayed three on-treatment visits for my clinic last Monday, and I converted 70% of my visits to telemedicine. However, I’m a genitourinary cancer specialist and the treatments I give are very different from others.

Lewis: The most difficult calculus is around adjuvant therapy. For metastatic patients, I am trying to use the least immunosuppressive regimen possible that will still control their disease. As you can imagine, it’s an assessment of competing risks.

Schapira: Patients who need essential anticancer therapy should still get it, but attempts to deintensify therapy should continue—for example, holding or postponing treatment without harm (based on evidence, not opinion). This may be possible for patients considering hormonal therapies for breast or prostate cancer.

Patients who need radiation should discuss the timing with their radiation oncologist. In some cases, it may be possible to delay treatment without affecting outcomes, but these decisions should be made carefully. Alternatively, shorter courses of radiation may be appropriate.
 

Have you advised your own patients differently given the high risk to cancer patients?

Kerr: We have factored potential infection with the virus into discussions where the benefits of chemotherapy are very marginal. This could tip the balance toward the patient deciding not to pursue chemotherapy.

Dizon: The data from China are not entirely crystal-clear. While they noted that people with active cancer and those who had a history of cancer are at increased risk for more severe infections and worse outcomes, the Chinese cohort was small, and compared with people without cancer, it tended to be much older and to be smokers (former or current). Having said this, we are counseling everyone about the importance of social distancing, washing hands, and not touching your face.

Lewis: If I have a complete blood count with a differential that includes lymphocytes, I can advise my lymphopenic patients (who are particularly vulnerable to viral infection) to take special precautions regarding social distancing in their own families.
 

Have any of your hospitalized patients been affected by policy changes to prepare beds/departments for the expected increase in COVID-19–positive patients?

Weber: Not yet.

Dizon: No, not at the moment.
 

Have you been asked to assist with other services or COVID-19 task forces?

Dizon: I am keenly involved in the preparations and modifications to procedures, including staffing decisions in outpatient, movement to telehealth, and work-from-home policies.

Lewis: I am engaged in system-wide COVID-19 efforts around oncology.

Kerr: Perhaps oddest of all, I am learning with some of our junior doctors to care for ventilated patients. I still consider myself enough of a general physician that I would hope to be able to contribute to the truly sick, but I accept that I do need an appropriate refresher course.

Bishal Gyawali, MD, PhD, medical oncologist at Queen’s University Cancer Research Institute: Queen’s Hospital medical students are now volunteering to help with daycare, groceries, and other tasks for staff who are working in the hospital.
 

Are you experiencing any shortages in personal protective equipment (PPE) at your center?

Miller: Some supplies are running short, though none are frankly out at this point. However, rationing and controls are in place to stretch the supplies as far as possible, including reusing some PPE.

Dizon: We are rationing face masks and N95 respirators, eye shields, and even surgical scrubs. We are talking about postponing elective surgery to save PPE but are not yet to that point. We’re asking that face masks be reused for at least 2 days, maybe longer. PPEs are one per day. Scrubs are kept secure.

Lewis: We are being very careful not to overuse PPE but currently have an adequate inventory. We have had to move gloves and masks to areas where they are not accessible to the general public, as otherwise they were being stolen (this started weeks ago).

Kerr: Our National Health System has an adequate supply of PPE equipment centrally, but there seems to be a problem with distribution, as some hospitals are reporting shortages.

Weber: Masks are in short supply, so they are being used for several days if not wet. We are short of plastic gowns and are using paper chemo gowns. Similar story at many places.

This article first appeared on Medscape.com.

In this edition of “Applying research to practice,” I examine a study suggesting that annual screening mammography does not reduce the risk of death from breast cancer in women aged 75 years and older. I also highlight a related editorial noting that we should optimize treatment as well as screening for breast cancer.

copyright/Thinkstock

Regular screening mammography in women aged 50-69 years prevents 21.3 breast cancer deaths among 10,000 women over a 10-year time period (Ann Intern Med. 2016 Feb 16;164[4]:244-55). However, in the published screening trials, few participants were older than 70 years of age.

More than half of women above age 74 receive annual mammograms (Health, United States, 2018. www.cdc.gov/nchs/data/hus/hus18.pdf). And more than a third of breast cancer deaths occur in women aged 70 years or older (CA Cancer J Clin. 2016 Mar-Apr;66[2]:96-114).

Do older women benefit from annual mammography to the same extent as younger women? Is there a point at which benefit ends?

To answer these questions, Xabier García-Albéniz, MD, PhD, of Harvard Medical School in Boston, and colleagues studied 1,058,013 women enrolled in Medicare during 2000-2008 (Ann Intern Med. 2020 Feb 25. doi: 10.7326/M18-1199).

The researchers examined data on patients aged 70-84 years who had a life expectancy of at least 10 years, at least one recent mammogram, and no history of breast cancer. The team emulated a prospective trial by examining deaths over an 8-year period for women aged 70 years and older who either continued or stopped screening mammography. The researchers conducted separate analyses for women aged 70-74 years and those aged 75-84 years.

Diagnoses of breast cancer were, not surprisingly, higher in the continued-screening group, but there were no major reductions in breast cancer–related deaths.

Among women aged 70-74 years, the estimated 8-year risk for breast cancer death was reduced for women who continued screening versus those who stopped it by one death per 1,000 women (hazard ratio, 0.78). Among women aged 75-84 years, the 8-year risk reduction was 0.07 deaths per 1,000 women (HR, 1.00).

The authors concluded that continuing mammographic screening past age 75 years resulted in no material difference in cancer-specific mortality over an 8-year time period, in comparison with stopping regular screening examinations.

Considering treatment as well as screening

For a variety of reasons (ethical, economic, methodologic), it is unreasonable to expect a randomized, clinical trial examining the value of mammography in older women. An informative alternative would be a well-designed, large-scale, population-based, observational study that takes into consideration potentially confounding variables of the binary strategies of continuing screening versus stopping it.

Although the 8-year risk of breast cancer in older women is not low among screened women – 5.5% in women aged 70-74 years and 5.8% in women aged 75-84 years – and mammography remains an effective screening tool, the effect of screening on breast cancer mortality appears to decline as women age.

In the editorial that accompanies the study by Dr. García-Albéniz and colleagues, Otis Brawley, MD, of Johns Hopkins University, Baltimore, highlighted the role of inadequate, ineffective, inconvenient, or poorly tolerated treatment in older women (Ann Intern Med. 2020 Feb 25. doi: 10.7326/M20-0429).

Dr. Brawley illustrated that focusing too much on screening diverts attention from the major driver of cancer mortality in older women: suboptimal treatment. That certainly has been the case for the dramatic impact of improved lung cancer treatment on mortality, despite a statistically significant impact of screening on lung cancer mortality as well.

As with lung cancer screening, Dr. Brawley describes the goal of defining “personalized screening recommendations” in breast cancer, or screening that is targeted to the highest-risk women and those who stand a high chance of benefiting from treatment if they are diagnosed with breast cancer.

As our population ages and health care expenditures continue to rise, there can be little disagreement that responsible use of cancer diagnostics will be as vital as judicious application of treatment.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

In this edition of “Applying research to practice,” I examine a study suggesting that annual screening mammography does not reduce the risk of death from breast cancer in women aged 75 years and older. I also highlight a related editorial noting that we should optimize treatment as well as screening for breast cancer.

copyright/Thinkstock

Regular screening mammography in women aged 50-69 years prevents 21.3 breast cancer deaths among 10,000 women over a 10-year time period (Ann Intern Med. 2016 Feb 16;164[4]:244-55). However, in the published screening trials, few participants were older than 70 years of age.

More than half of women above age 74 receive annual mammograms (Health, United States, 2018. www.cdc.gov/nchs/data/hus/hus18.pdf). And more than a third of breast cancer deaths occur in women aged 70 years or older (CA Cancer J Clin. 2016 Mar-Apr;66[2]:96-114).

Do older women benefit from annual mammography to the same extent as younger women? Is there a point at which benefit ends?

To answer these questions, Xabier García-Albéniz, MD, PhD, of Harvard Medical School in Boston, and colleagues studied 1,058,013 women enrolled in Medicare during 2000-2008 (Ann Intern Med. 2020 Feb 25. doi: 10.7326/M18-1199).

The researchers examined data on patients aged 70-84 years who had a life expectancy of at least 10 years, at least one recent mammogram, and no history of breast cancer. The team emulated a prospective trial by examining deaths over an 8-year period for women aged 70 years and older who either continued or stopped screening mammography. The researchers conducted separate analyses for women aged 70-74 years and those aged 75-84 years.

Diagnoses of breast cancer were, not surprisingly, higher in the continued-screening group, but there were no major reductions in breast cancer–related deaths.

Among women aged 70-74 years, the estimated 8-year risk for breast cancer death was reduced for women who continued screening versus those who stopped it by one death per 1,000 women (hazard ratio, 0.78). Among women aged 75-84 years, the 8-year risk reduction was 0.07 deaths per 1,000 women (HR, 1.00).

The authors concluded that continuing mammographic screening past age 75 years resulted in no material difference in cancer-specific mortality over an 8-year time period, in comparison with stopping regular screening examinations.

Considering treatment as well as screening

For a variety of reasons (ethical, economic, methodologic), it is unreasonable to expect a randomized, clinical trial examining the value of mammography in older women. An informative alternative would be a well-designed, large-scale, population-based, observational study that takes into consideration potentially confounding variables of the binary strategies of continuing screening versus stopping it.

Although the 8-year risk of breast cancer in older women is not low among screened women – 5.5% in women aged 70-74 years and 5.8% in women aged 75-84 years – and mammography remains an effective screening tool, the effect of screening on breast cancer mortality appears to decline as women age.

In the editorial that accompanies the study by Dr. García-Albéniz and colleagues, Otis Brawley, MD, of Johns Hopkins University, Baltimore, highlighted the role of inadequate, ineffective, inconvenient, or poorly tolerated treatment in older women (Ann Intern Med. 2020 Feb 25. doi: 10.7326/M20-0429).

Dr. Brawley illustrated that focusing too much on screening diverts attention from the major driver of cancer mortality in older women: suboptimal treatment. That certainly has been the case for the dramatic impact of improved lung cancer treatment on mortality, despite a statistically significant impact of screening on lung cancer mortality as well.

As with lung cancer screening, Dr. Brawley describes the goal of defining “personalized screening recommendations” in breast cancer, or screening that is targeted to the highest-risk women and those who stand a high chance of benefiting from treatment if they are diagnosed with breast cancer.

As our population ages and health care expenditures continue to rise, there can be little disagreement that responsible use of cancer diagnostics will be as vital as judicious application of treatment.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

In this edition of “Applying research to practice,” I examine a study suggesting that annual screening mammography does not reduce the risk of death from breast cancer in women aged 75 years and older. I also highlight a related editorial noting that we should optimize treatment as well as screening for breast cancer.

copyright/Thinkstock

Regular screening mammography in women aged 50-69 years prevents 21.3 breast cancer deaths among 10,000 women over a 10-year time period (Ann Intern Med. 2016 Feb 16;164[4]:244-55). However, in the published screening trials, few participants were older than 70 years of age.

More than half of women above age 74 receive annual mammograms (Health, United States, 2018. www.cdc.gov/nchs/data/hus/hus18.pdf). And more than a third of breast cancer deaths occur in women aged 70 years or older (CA Cancer J Clin. 2016 Mar-Apr;66[2]:96-114).

Do older women benefit from annual mammography to the same extent as younger women? Is there a point at which benefit ends?

To answer these questions, Xabier García-Albéniz, MD, PhD, of Harvard Medical School in Boston, and colleagues studied 1,058,013 women enrolled in Medicare during 2000-2008 (Ann Intern Med. 2020 Feb 25. doi: 10.7326/M18-1199).

The researchers examined data on patients aged 70-84 years who had a life expectancy of at least 10 years, at least one recent mammogram, and no history of breast cancer. The team emulated a prospective trial by examining deaths over an 8-year period for women aged 70 years and older who either continued or stopped screening mammography. The researchers conducted separate analyses for women aged 70-74 years and those aged 75-84 years.

Diagnoses of breast cancer were, not surprisingly, higher in the continued-screening group, but there were no major reductions in breast cancer–related deaths.

Among women aged 70-74 years, the estimated 8-year risk for breast cancer death was reduced for women who continued screening versus those who stopped it by one death per 1,000 women (hazard ratio, 0.78). Among women aged 75-84 years, the 8-year risk reduction was 0.07 deaths per 1,000 women (HR, 1.00).

The authors concluded that continuing mammographic screening past age 75 years resulted in no material difference in cancer-specific mortality over an 8-year time period, in comparison with stopping regular screening examinations.

Considering treatment as well as screening

For a variety of reasons (ethical, economic, methodologic), it is unreasonable to expect a randomized, clinical trial examining the value of mammography in older women. An informative alternative would be a well-designed, large-scale, population-based, observational study that takes into consideration potentially confounding variables of the binary strategies of continuing screening versus stopping it.

Although the 8-year risk of breast cancer in older women is not low among screened women – 5.5% in women aged 70-74 years and 5.8% in women aged 75-84 years – and mammography remains an effective screening tool, the effect of screening on breast cancer mortality appears to decline as women age.

In the editorial that accompanies the study by Dr. García-Albéniz and colleagues, Otis Brawley, MD, of Johns Hopkins University, Baltimore, highlighted the role of inadequate, ineffective, inconvenient, or poorly tolerated treatment in older women (Ann Intern Med. 2020 Feb 25. doi: 10.7326/M20-0429).

Dr. Brawley illustrated that focusing too much on screening diverts attention from the major driver of cancer mortality in older women: suboptimal treatment. That certainly has been the case for the dramatic impact of improved lung cancer treatment on mortality, despite a statistically significant impact of screening on lung cancer mortality as well.

As with lung cancer screening, Dr. Brawley describes the goal of defining “personalized screening recommendations” in breast cancer, or screening that is targeted to the highest-risk women and those who stand a high chance of benefiting from treatment if they are diagnosed with breast cancer.

As our population ages and health care expenditures continue to rise, there can be little disagreement that responsible use of cancer diagnostics will be as vital as judicious application of treatment.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
 

Even in the midst of the COVID-19 pandemic, cancer care must go on, but changes may need to be made in the way some care is delivered.

“We’re headed for a time when there will be significant disruptions in the care of patients with cancer,” said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS), in a statement. “For some it may be as straightforward as a delay in having elective surgery. For others it may be delaying preventive care or adjuvant chemotherapy that’s meant to keep cancer from returning or rescheduling appointments.”

Lichtenfeld emphasized that cancer care teams are going to do the best they can to deliver care to those most in need. However, even in those circumstances, it won’t be life as usual. “It will require patience on everyone’s part as we go through this pandemic,” he said.

“The way we treat cancer over the next few months will change enormously,” writes a British oncologist in an article published in the Guardian.

“As oncologists, we will have to find a tenuous balance between undertreating people with cancer, resulting in more deaths from the disease in the medium to long term, and increasing deaths from COVID-19 in a vulnerable patient population. Alongside our patients we will have to make difficult decisions regarding treatments, with only low-quality evidence to guide us,” writes Lucy Gossage, MD, consultant oncologist at Nottingham University Hospital, UK.

The evidence to date (from reports from China in Lancet Oncology) suggests that people with cancer have a significantly higher risk of severe illness resulting in intensive care admissions or death when infected with COVID-19, particularly if they recently had chemotherapy or surgery.

“Many of the oncology treatments we currently use, especially those given after surgery to reduce risk of cancer recurrence, have relatively small benefits,” she writes.

“In the current climate, the balance of offering these treatments may shift; a small reduction in risk of cancer recurrence over the next 5 years may be outweighed by the potential for a short-term increase in risk of death from COVID-19. In the long term, more people’s cancer will return if we aren’t able to offer these treatments,” she adds.

Postpone Routine Screening

One thing that can go on the back burner for now is routine cancer screening, which can be postponed for now in order to conserve health system resources and reduce contact with healthcare facilities, says the ACS.

“Patients seeking routine cancer screenings should delay those until further notice,” said Lichtenfeld. “While timely screening is important, the need to prevent the spread of coronavirus and to reduce the strain on the medical system is more important right now.”

But as soon as restrictions to slow the spread of COVID-19 are lifted and routine visits to health facilities are safe, regular screening tests should be rescheduled.

Guidance From ASCO

The American Society of Clinical Oncology (ASCO) has issued new guidance on caring for patients with cancer during the COVID-19 outbreak.

First and foremost, ASCO encourages providers, facilities, and anyone caring for patients with cancer to follow the existing guidelines from the Center for Disease Control and Prevention when possible.

ASCO highlights the CDC’s general recommendation for healthcare facilities that suggests “elective surgeries” at inpatient facilities be rescheduled if possible, which has also been recommended by the American College of Surgeons.

However, in many cases, cancer surgery is not elective but essential, it points out. So this is largely an individual determination that clinicians and patients will need to make, taking into account the potential harms of delaying needed cancer-related surgery.

Systemic treatments, including chemotherapy and immunotherapy, leave cancer patients vulnerable to infection, but ASCO says there is no direct evidence to support changes in regimens during the pandemic. Therefore, routinely stopping anticancer or immunosuppressive therapy is not recommended, as the balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection remains very unclear.

Clinical decisions must be individualized, ASCO emphasized, and suggested the following practice points be considered:

• For patients already in deep remission who are receiving maintenance therapy, stopping treatment may be an option.
• Some patients may be able to switch from IV to oral therapies, which would decrease the frequency of clinic visits.
• Decisions on modifying or withholding chemotherapy need to consider both the indication and goals of care, as well as where the patient is in the treatment regimen and tolerance to the therapy. As an example, the risk–benefit assessment for proceeding with chemotherapy in patients with untreated extensive small-cell lung cancer is quite different than proceeding with maintenance pemetrexed for metastatic non–small cell lung cancer.
• If local coronavirus transmission is an issue at a particular cancer center, reasonable options may include taking a 2-week treatment break or arranging treatment at a different facility.
• Evaluate if home infusion is medically and logistically feasible.
• In some settings, delaying or modifying adjuvant treatment presents a higher risk of compromised disease control and long-term survival than in others, but in cases where the absolute benefit of adjuvant chemotherapy may be quite small and other options are available, the risk of COVID-19 may be considered an additional factor when evaluating care.

Delay Stem Cell Transplants

For patients who are candidates for allogeneic stem cell transplantation, a delay may be reasonable if the patient is currently well controlled with conventional treatment, ASCO comments. It also directs clinicians to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy and from the European Society for Blood and Marrow Transplantation regarding this issue.

Finally, there is also the question of prophylactic antiviral therapy: Should it be considered for cancer patients undergoing active therapy?

The answer to that question is currently unknown, says ASCO, but “this is an active area of research and evidence may be available at any time.”

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
 

Even in the midst of the COVID-19 pandemic, cancer care must go on, but changes may need to be made in the way some care is delivered.

“We’re headed for a time when there will be significant disruptions in the care of patients with cancer,” said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS), in a statement. “For some it may be as straightforward as a delay in having elective surgery. For others it may be delaying preventive care or adjuvant chemotherapy that’s meant to keep cancer from returning or rescheduling appointments.”

Lichtenfeld emphasized that cancer care teams are going to do the best they can to deliver care to those most in need. However, even in those circumstances, it won’t be life as usual. “It will require patience on everyone’s part as we go through this pandemic,” he said.

“The way we treat cancer over the next few months will change enormously,” writes a British oncologist in an article published in the Guardian.

“As oncologists, we will have to find a tenuous balance between undertreating people with cancer, resulting in more deaths from the disease in the medium to long term, and increasing deaths from COVID-19 in a vulnerable patient population. Alongside our patients we will have to make difficult decisions regarding treatments, with only low-quality evidence to guide us,” writes Lucy Gossage, MD, consultant oncologist at Nottingham University Hospital, UK.

The evidence to date (from reports from China in Lancet Oncology) suggests that people with cancer have a significantly higher risk of severe illness resulting in intensive care admissions or death when infected with COVID-19, particularly if they recently had chemotherapy or surgery.

“Many of the oncology treatments we currently use, especially those given after surgery to reduce risk of cancer recurrence, have relatively small benefits,” she writes.

“In the current climate, the balance of offering these treatments may shift; a small reduction in risk of cancer recurrence over the next 5 years may be outweighed by the potential for a short-term increase in risk of death from COVID-19. In the long term, more people’s cancer will return if we aren’t able to offer these treatments,” she adds.

Postpone Routine Screening

One thing that can go on the back burner for now is routine cancer screening, which can be postponed for now in order to conserve health system resources and reduce contact with healthcare facilities, says the ACS.

“Patients seeking routine cancer screenings should delay those until further notice,” said Lichtenfeld. “While timely screening is important, the need to prevent the spread of coronavirus and to reduce the strain on the medical system is more important right now.”

But as soon as restrictions to slow the spread of COVID-19 are lifted and routine visits to health facilities are safe, regular screening tests should be rescheduled.

Guidance From ASCO

The American Society of Clinical Oncology (ASCO) has issued new guidance on caring for patients with cancer during the COVID-19 outbreak.

First and foremost, ASCO encourages providers, facilities, and anyone caring for patients with cancer to follow the existing guidelines from the Center for Disease Control and Prevention when possible.

ASCO highlights the CDC’s general recommendation for healthcare facilities that suggests “elective surgeries” at inpatient facilities be rescheduled if possible, which has also been recommended by the American College of Surgeons.

However, in many cases, cancer surgery is not elective but essential, it points out. So this is largely an individual determination that clinicians and patients will need to make, taking into account the potential harms of delaying needed cancer-related surgery.

Systemic treatments, including chemotherapy and immunotherapy, leave cancer patients vulnerable to infection, but ASCO says there is no direct evidence to support changes in regimens during the pandemic. Therefore, routinely stopping anticancer or immunosuppressive therapy is not recommended, as the balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection remains very unclear.

Clinical decisions must be individualized, ASCO emphasized, and suggested the following practice points be considered:

• For patients already in deep remission who are receiving maintenance therapy, stopping treatment may be an option.
• Some patients may be able to switch from IV to oral therapies, which would decrease the frequency of clinic visits.
• Decisions on modifying or withholding chemotherapy need to consider both the indication and goals of care, as well as where the patient is in the treatment regimen and tolerance to the therapy. As an example, the risk–benefit assessment for proceeding with chemotherapy in patients with untreated extensive small-cell lung cancer is quite different than proceeding with maintenance pemetrexed for metastatic non–small cell lung cancer.
• If local coronavirus transmission is an issue at a particular cancer center, reasonable options may include taking a 2-week treatment break or arranging treatment at a different facility.
• Evaluate if home infusion is medically and logistically feasible.
• In some settings, delaying or modifying adjuvant treatment presents a higher risk of compromised disease control and long-term survival than in others, but in cases where the absolute benefit of adjuvant chemotherapy may be quite small and other options are available, the risk of COVID-19 may be considered an additional factor when evaluating care.

Delay Stem Cell Transplants

For patients who are candidates for allogeneic stem cell transplantation, a delay may be reasonable if the patient is currently well controlled with conventional treatment, ASCO comments. It also directs clinicians to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy and from the European Society for Blood and Marrow Transplantation regarding this issue.

Finally, there is also the question of prophylactic antiviral therapy: Should it be considered for cancer patients undergoing active therapy?

The answer to that question is currently unknown, says ASCO, but “this is an active area of research and evidence may be available at any time.”

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
 

Even in the midst of the COVID-19 pandemic, cancer care must go on, but changes may need to be made in the way some care is delivered.

“We’re headed for a time when there will be significant disruptions in the care of patients with cancer,” said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS), in a statement. “For some it may be as straightforward as a delay in having elective surgery. For others it may be delaying preventive care or adjuvant chemotherapy that’s meant to keep cancer from returning or rescheduling appointments.”

Lichtenfeld emphasized that cancer care teams are going to do the best they can to deliver care to those most in need. However, even in those circumstances, it won’t be life as usual. “It will require patience on everyone’s part as we go through this pandemic,” he said.

“The way we treat cancer over the next few months will change enormously,” writes a British oncologist in an article published in the Guardian.

“As oncologists, we will have to find a tenuous balance between undertreating people with cancer, resulting in more deaths from the disease in the medium to long term, and increasing deaths from COVID-19 in a vulnerable patient population. Alongside our patients we will have to make difficult decisions regarding treatments, with only low-quality evidence to guide us,” writes Lucy Gossage, MD, consultant oncologist at Nottingham University Hospital, UK.

The evidence to date (from reports from China in Lancet Oncology) suggests that people with cancer have a significantly higher risk of severe illness resulting in intensive care admissions or death when infected with COVID-19, particularly if they recently had chemotherapy or surgery.

“Many of the oncology treatments we currently use, especially those given after surgery to reduce risk of cancer recurrence, have relatively small benefits,” she writes.

“In the current climate, the balance of offering these treatments may shift; a small reduction in risk of cancer recurrence over the next 5 years may be outweighed by the potential for a short-term increase in risk of death from COVID-19. In the long term, more people’s cancer will return if we aren’t able to offer these treatments,” she adds.

Postpone Routine Screening

One thing that can go on the back burner for now is routine cancer screening, which can be postponed for now in order to conserve health system resources and reduce contact with healthcare facilities, says the ACS.

“Patients seeking routine cancer screenings should delay those until further notice,” said Lichtenfeld. “While timely screening is important, the need to prevent the spread of coronavirus and to reduce the strain on the medical system is more important right now.”

But as soon as restrictions to slow the spread of COVID-19 are lifted and routine visits to health facilities are safe, regular screening tests should be rescheduled.

Guidance From ASCO

The American Society of Clinical Oncology (ASCO) has issued new guidance on caring for patients with cancer during the COVID-19 outbreak.

First and foremost, ASCO encourages providers, facilities, and anyone caring for patients with cancer to follow the existing guidelines from the Center for Disease Control and Prevention when possible.

ASCO highlights the CDC’s general recommendation for healthcare facilities that suggests “elective surgeries” at inpatient facilities be rescheduled if possible, which has also been recommended by the American College of Surgeons.

However, in many cases, cancer surgery is not elective but essential, it points out. So this is largely an individual determination that clinicians and patients will need to make, taking into account the potential harms of delaying needed cancer-related surgery.

Systemic treatments, including chemotherapy and immunotherapy, leave cancer patients vulnerable to infection, but ASCO says there is no direct evidence to support changes in regimens during the pandemic. Therefore, routinely stopping anticancer or immunosuppressive therapy is not recommended, as the balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection remains very unclear.

Clinical decisions must be individualized, ASCO emphasized, and suggested the following practice points be considered:

• For patients already in deep remission who are receiving maintenance therapy, stopping treatment may be an option.
• Some patients may be able to switch from IV to oral therapies, which would decrease the frequency of clinic visits.
• Decisions on modifying or withholding chemotherapy need to consider both the indication and goals of care, as well as where the patient is in the treatment regimen and tolerance to the therapy. As an example, the risk–benefit assessment for proceeding with chemotherapy in patients with untreated extensive small-cell lung cancer is quite different than proceeding with maintenance pemetrexed for metastatic non–small cell lung cancer.
• If local coronavirus transmission is an issue at a particular cancer center, reasonable options may include taking a 2-week treatment break or arranging treatment at a different facility.
• Evaluate if home infusion is medically and logistically feasible.
• In some settings, delaying or modifying adjuvant treatment presents a higher risk of compromised disease control and long-term survival than in others, but in cases where the absolute benefit of adjuvant chemotherapy may be quite small and other options are available, the risk of COVID-19 may be considered an additional factor when evaluating care.

Delay Stem Cell Transplants

For patients who are candidates for allogeneic stem cell transplantation, a delay may be reasonable if the patient is currently well controlled with conventional treatment, ASCO comments. It also directs clinicians to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy and from the European Society for Blood and Marrow Transplantation regarding this issue.

Finally, there is also the question of prophylactic antiviral therapy: Should it be considered for cancer patients undergoing active therapy?

The answer to that question is currently unknown, says ASCO, but “this is an active area of research and evidence may be available at any time.”

This article first appeared on Medscape.com.

In December, at a major breast cancer conference, some attendees couldn’t find a seat and were told to leave an overcrowded session on immunotherapy for metastatic triple-negative breast cancer (TNBC). They refused, and pushed in to hear what was being said.

The crowd might have been surprised to learn that the main draw of the event, a successful new drug, was not all it might have been for women with the disease, being handicapped by a test that determines who is eligible for it.

“That room was overpacked ― there were five people deep against the wall. ... It was amazing,” said Janice Cowden of Bradenton, Florida. She attended the meeting, the San Antonio Breast Cancer Symposium, as a patient advocate.

Cowden lives with metastatic TNBC, which is known for poor prognoses, aggressiveness, and a lack of targeted treatment options. “Stage IV is a state of desperation. We just want something to work,” she said.

That’s why the conference room was packed – the session was focused on something that had been found to work – the immunotherapy atezolizumab (Tecentriq, Genentech/Roche).

Atezolizumab had recently been conditionally approved for first-line use in advanced TNBC, having been shown to significantly slow disease progression and, in some patients, to possibly improve survival. A pair of medical oncologists reviewed the clinical trial data during the session.

One important point from the trial data was that the benefit was greater in patients whose tumors had the biomarker PD-L1, and so the Food and Drug Administration approval of the drug specified that it should be used only in those patients.

The drug approval was accompanied by approval of a companion diagnostic test used to identify this PD-L1-positive subgroup of patients, the Ventana SP142 Assay (Roche Diagnostics).

At the meeting, pathologist David Rimm, MD, of Yale University, New Haven, Connecticut, discussed the biomarker PD-L1 and the test. Rimm had a subtle but unsettling message about the crucial test: that the SP142 diagnostic assay, when used by increasing numbers of pathologists, resulted in increasing rates of PD-L1 scores that were not concordant.

A related meeting poster, presented the next day with Rimm as senior author, was more explicit and concluded that “more than half of the pathologists in real-world situations may mis- assign” patient scores with SP142 (and another Roche assay) because of wide variability in readouts.

“They’ve made a test that is inadequate – it just doesn’t work. It’s like flipping a coin,” he told Medscape Medical News about Roche’s SP142 assay in everyday practice.

The general problem is not a new one – for some years there have been problems with the use of PD-L1 as a biomarker for immunotherapy and with assays for that biomarker, with many groups questioning both accuracy and reproducibility. But the problems with SP142 are “the most egregious,” said Rimm, who has served as a paid consultant to Roche Diagnostics in the past.

In clinical practice, Rimm’s overall message is that because of the difficulty of reading SP142 assay results, some TNBC patients who were PD-L1-positive would not get the drug, and some who were not positive would get the drug.

Patient advocate Cowden was not worried about overtreatment. She was concerned about patients who “might die without receiving a potentially life-extending treatment.”

In an essay in the Pathologist, Rimm echoed that sentiment about undertreatment (as well as overtreatment) with atezolizumab for breast cancer: “In all cases, the patients are the potential victims, but this appears to be completely under the radar of the hype surrounding this new drug.”
 

Roche Disputes Problems With Assay

Roche, manufacturer of both atezolizumab and the companion diagnostic test, disputes that there is a problem.

The FDA and multiple health authorities worldwide have approved atezolizumab and the companion diagnostic SP142 assay for use in TNBC, points out Eslie Dennis, MD, vice president of medical affairs at Roche Tissue Diagnostics.

“The role of a companion diagnostic assay is to discriminate between responders and non-responders for a specific therapeutic product in a specific indication, with a cut-off based on clinical outcomes,” she wrote in an email to Medscape Medical News.

Data from the pivotal IMpassion130 trial show that the assay was effective at that task. Among the 369 patients in the 902-patient trial whose tumors were ≥1% positive for PD-L1, those treated with atezolizumab (and nab-paclitaxel; n = 185) had a median progression-free survival (PFS) of 7.4 months, vs. 4.8 months among those treated with placebo (and nab-paclitaxel; n = 184) (P < .0001).

“Exploratory analysis showed no [PFS] benefit in PD-L1-negative patients as tested by the SP142 assay [in IMpassion130],” Dennis and three other physicians write in a reply to Rimm in a letter published in July 2019 in the Pathologist.

The same held true for overall survival in exploratory analysis – there was no benefit with atezolizumab among the PD-L1-negative patients, they write.

Notably, overall survival benefit for patients who were PD-L1 positive was about 10 months (at the first interim analysis; at the second analysis, the benefit dropped to 7 months and was not statistically significant).

But Rimm points out that the pivotal trial used only one pathologist in a central lab to determine PD-L1 status, who was undoubtedly an expert with the SP142 assay.

Further, Rimm observes that additional data submitted to the FDA to show that SP142 test results are reproducible outside of the pivotal trial setting were performed with only three pathologists and thus unsurprisingly yielded high rates of agreement – all above 90%.

The data from both of these circumstances are problematic, Rimm said, because in the real world, hundreds of pathologists will score the SP142 assay – all in the context of a busy day reading a variety of other tests for other diseases.

It’s one thing to get an FDA approval for an assay, and it’s another thing to be a reliable, well-functioning assay in the real world, he summarized.

Last year, Roberto Salgado, MD, PhD, a pathologist at the Université Libre de Bruxelles, Belgium, commented that “a positive phase III trial should not be taken as a guarantee that the assay used in the trial can be implemented in daily practice” in an opinion piece in the Pathologist.
 

SP142 Identifies the “Fewest Possible Patients”

The SP142 assay has been shown in multiple studies to have lower sensitivity for PD-L1 than other competing PD-L1 assays, said Rimm, citing examples such as a 2017 study and a 2018 study.

Angela DeMichele, MD, a medical oncologist at the University of Pennsylvania in Philadelphia, agreed and explained what that meant in practical terms for women whose tumors are tested with SP142. “It means that the test is going to identify the fewest possible PD-L1-positive patients [relative to the other available assays],” she said. “It [the SP142 assay] is far from a perfect test for this situation,” added DeMichele, an expert on biomarkers in breast cancer clinical trials.

She said that biomarker tests, like many products of science, tend to become dated with the passage of time, as more is learned about the target and new assays are developed. “Unfortunately, you can’t change assays midstream,” said DeMichele. She has received a grant from Roche and Stand Up to Cancer to study atezolizumab and another drug in a clinical trial among patients with metastatic TNBC who have minimal residual disease.

DeMichele also said that “David Rimm is one of the most knowledgeable people in the world about this issue.”

But DeMichelle also points out the practical: “We’re stuck as clinicians” because regulatory bodies and insurance companies only pay for atezolizumab when the SP142 assay indicates PD-L1 positivity. That’s not the case in Europe, where health authorities do not specify which PD-L1 assay is to be used with atezolizumab for breast cancer, pointed out Belgium’s Salgado last year.
 

Another Level of Complexity

At the immunotherapy session in San Antonio, Rimm discussed the results of a study of 68 TNBC archived cases in which specimens were stained with the SP142 assay at Yale and were distributed via electronic images to 19 pathologists at 14 institutions across the United States for PD-L1 scoring.

The study, coauthored by academics from Iowa, Texas A&M, UC San Diego, Mayo Clinic, Memorial Sloan Kettering, and others, used a novel method to determine the minimum number of evaluators needed to estimate “concordance” or agreement about a test result among large numbers of readers. The consensus/agreement was as high as 80% when eight or fewer pathologists’ scores were compared, but was as low as 40% when results from more than eight pathologists were included, said Rimm.

These are some of the data that led him to declare that using the assay is no better than flipping a coin.

Yes, PD-L1 testing is a challenge, and it has “introduced another level of complexity” for pathologists in reading assays, write experts Emina Torlakovic, MD, University of Saskatchewan, Canada, and Allen Gown, MD, PhenoPath Laboratories, Seattle, in response to Rimm last year.

But there is “poor” consensus among pathologists, they point out, “for many scoring systems that are still clinically applied (such as Gleason grading).” Consensus “improves with education and training,” the pair add. To that end, Roche has initiated a global training program for pathologists using the SP142 assay for TNBC. At San Antonio, Roche’s Dennis reported that among 432 pathologists from 58 countries, there was overall agreement of 98.2% in scoring assays.

Rimm commented that such high agreement would not be a surprise if testing took place soon after any such training program.

In an email to Medscape Medical News, Torlakovic encouraged pathologists who wish to practice their skill in interpreting assays, including SP142, to visit CBQAReadout.ca, a testing site. The site, which was founded by Torlakovic and may be one of a kind, offers CME credits and is sponsored by independent pathology organizations, such as CAP-ACP and the Saskatchewan Health Authority, as well as pharmaceutical companies, including Roche.

No Clue

Patient advocate Cowden believes the controversy about PD-L1 testing for atezolizumab is largely unknown among breast cancer patients. She learned about SP142 assay ambiguities in San Antonio, when the Florida Breast Cancer Foundation funded her trip to the meeting and the Alamo Breast Cancer Foundation asked her to write a report on Rimm’s presentation.

Cowden is a member of a Facebook group for stage IV TNBC, which has about 1500 members. She estimates that 75%-80% would be willing to try atezolizumab “no matter what,” meaning they don’t care about PD-L1 positivity being associated with efficacy.

The Facebook group members “know there is a test and if you are positive, there is an immunotherapy for their breast cancer,” said Cowden.

None know that women may be excluded from treatment because of shortcomings with the SP142 test. “They have no clue,” she said.

Rimm and DeMichele have financial ties to Roche and other companies. Dennis is an employee of Roche. Torlakovic has ties to multiple companies, including Roche, for whom she has acted as a paid consultant, grant recipient, and paid lecturer. Gown did not respond to a request for financial disclosures. Cowden reports no relevant financial relationships.

This article first appeared on Medscape.com.

In December, at a major breast cancer conference, some attendees couldn’t find a seat and were told to leave an overcrowded session on immunotherapy for metastatic triple-negative breast cancer (TNBC). They refused, and pushed in to hear what was being said.

The crowd might have been surprised to learn that the main draw of the event, a successful new drug, was not all it might have been for women with the disease, being handicapped by a test that determines who is eligible for it.

“That room was overpacked ― there were five people deep against the wall. ... It was amazing,” said Janice Cowden of Bradenton, Florida. She attended the meeting, the San Antonio Breast Cancer Symposium, as a patient advocate.

Cowden lives with metastatic TNBC, which is known for poor prognoses, aggressiveness, and a lack of targeted treatment options. “Stage IV is a state of desperation. We just want something to work,” she said.

That’s why the conference room was packed – the session was focused on something that had been found to work – the immunotherapy atezolizumab (Tecentriq, Genentech/Roche).

Atezolizumab had recently been conditionally approved for first-line use in advanced TNBC, having been shown to significantly slow disease progression and, in some patients, to possibly improve survival. A pair of medical oncologists reviewed the clinical trial data during the session.

One important point from the trial data was that the benefit was greater in patients whose tumors had the biomarker PD-L1, and so the Food and Drug Administration approval of the drug specified that it should be used only in those patients.

The drug approval was accompanied by approval of a companion diagnostic test used to identify this PD-L1-positive subgroup of patients, the Ventana SP142 Assay (Roche Diagnostics).

At the meeting, pathologist David Rimm, MD, of Yale University, New Haven, Connecticut, discussed the biomarker PD-L1 and the test. Rimm had a subtle but unsettling message about the crucial test: that the SP142 diagnostic assay, when used by increasing numbers of pathologists, resulted in increasing rates of PD-L1 scores that were not concordant.

A related meeting poster, presented the next day with Rimm as senior author, was more explicit and concluded that “more than half of the pathologists in real-world situations may mis- assign” patient scores with SP142 (and another Roche assay) because of wide variability in readouts.

“They’ve made a test that is inadequate – it just doesn’t work. It’s like flipping a coin,” he told Medscape Medical News about Roche’s SP142 assay in everyday practice.

The general problem is not a new one – for some years there have been problems with the use of PD-L1 as a biomarker for immunotherapy and with assays for that biomarker, with many groups questioning both accuracy and reproducibility. But the problems with SP142 are “the most egregious,” said Rimm, who has served as a paid consultant to Roche Diagnostics in the past.

In clinical practice, Rimm’s overall message is that because of the difficulty of reading SP142 assay results, some TNBC patients who were PD-L1-positive would not get the drug, and some who were not positive would get the drug.

Patient advocate Cowden was not worried about overtreatment. She was concerned about patients who “might die without receiving a potentially life-extending treatment.”

In an essay in the Pathologist, Rimm echoed that sentiment about undertreatment (as well as overtreatment) with atezolizumab for breast cancer: “In all cases, the patients are the potential victims, but this appears to be completely under the radar of the hype surrounding this new drug.”
 

Roche Disputes Problems With Assay

Roche, manufacturer of both atezolizumab and the companion diagnostic test, disputes that there is a problem.

The FDA and multiple health authorities worldwide have approved atezolizumab and the companion diagnostic SP142 assay for use in TNBC, points out Eslie Dennis, MD, vice president of medical affairs at Roche Tissue Diagnostics.

“The role of a companion diagnostic assay is to discriminate between responders and non-responders for a specific therapeutic product in a specific indication, with a cut-off based on clinical outcomes,” she wrote in an email to Medscape Medical News.

Data from the pivotal IMpassion130 trial show that the assay was effective at that task. Among the 369 patients in the 902-patient trial whose tumors were ≥1% positive for PD-L1, those treated with atezolizumab (and nab-paclitaxel; n = 185) had a median progression-free survival (PFS) of 7.4 months, vs. 4.8 months among those treated with placebo (and nab-paclitaxel; n = 184) (P < .0001).

“Exploratory analysis showed no [PFS] benefit in PD-L1-negative patients as tested by the SP142 assay [in IMpassion130],” Dennis and three other physicians write in a reply to Rimm in a letter published in July 2019 in the Pathologist.

The same held true for overall survival in exploratory analysis – there was no benefit with atezolizumab among the PD-L1-negative patients, they write.

Notably, overall survival benefit for patients who were PD-L1 positive was about 10 months (at the first interim analysis; at the second analysis, the benefit dropped to 7 months and was not statistically significant).

But Rimm points out that the pivotal trial used only one pathologist in a central lab to determine PD-L1 status, who was undoubtedly an expert with the SP142 assay.

Further, Rimm observes that additional data submitted to the FDA to show that SP142 test results are reproducible outside of the pivotal trial setting were performed with only three pathologists and thus unsurprisingly yielded high rates of agreement – all above 90%.

The data from both of these circumstances are problematic, Rimm said, because in the real world, hundreds of pathologists will score the SP142 assay – all in the context of a busy day reading a variety of other tests for other diseases.

It’s one thing to get an FDA approval for an assay, and it’s another thing to be a reliable, well-functioning assay in the real world, he summarized.

Last year, Roberto Salgado, MD, PhD, a pathologist at the Université Libre de Bruxelles, Belgium, commented that “a positive phase III trial should not be taken as a guarantee that the assay used in the trial can be implemented in daily practice” in an opinion piece in the Pathologist.
 

SP142 Identifies the “Fewest Possible Patients”

The SP142 assay has been shown in multiple studies to have lower sensitivity for PD-L1 than other competing PD-L1 assays, said Rimm, citing examples such as a 2017 study and a 2018 study.

Angela DeMichele, MD, a medical oncologist at the University of Pennsylvania in Philadelphia, agreed and explained what that meant in practical terms for women whose tumors are tested with SP142. “It means that the test is going to identify the fewest possible PD-L1-positive patients [relative to the other available assays],” she said. “It [the SP142 assay] is far from a perfect test for this situation,” added DeMichele, an expert on biomarkers in breast cancer clinical trials.

She said that biomarker tests, like many products of science, tend to become dated with the passage of time, as more is learned about the target and new assays are developed. “Unfortunately, you can’t change assays midstream,” said DeMichele. She has received a grant from Roche and Stand Up to Cancer to study atezolizumab and another drug in a clinical trial among patients with metastatic TNBC who have minimal residual disease.

DeMichele also said that “David Rimm is one of the most knowledgeable people in the world about this issue.”

But DeMichelle also points out the practical: “We’re stuck as clinicians” because regulatory bodies and insurance companies only pay for atezolizumab when the SP142 assay indicates PD-L1 positivity. That’s not the case in Europe, where health authorities do not specify which PD-L1 assay is to be used with atezolizumab for breast cancer, pointed out Belgium’s Salgado last year.
 

Another Level of Complexity

At the immunotherapy session in San Antonio, Rimm discussed the results of a study of 68 TNBC archived cases in which specimens were stained with the SP142 assay at Yale and were distributed via electronic images to 19 pathologists at 14 institutions across the United States for PD-L1 scoring.

The study, coauthored by academics from Iowa, Texas A&M, UC San Diego, Mayo Clinic, Memorial Sloan Kettering, and others, used a novel method to determine the minimum number of evaluators needed to estimate “concordance” or agreement about a test result among large numbers of readers. The consensus/agreement was as high as 80% when eight or fewer pathologists’ scores were compared, but was as low as 40% when results from more than eight pathologists were included, said Rimm.

These are some of the data that led him to declare that using the assay is no better than flipping a coin.

Yes, PD-L1 testing is a challenge, and it has “introduced another level of complexity” for pathologists in reading assays, write experts Emina Torlakovic, MD, University of Saskatchewan, Canada, and Allen Gown, MD, PhenoPath Laboratories, Seattle, in response to Rimm last year.

But there is “poor” consensus among pathologists, they point out, “for many scoring systems that are still clinically applied (such as Gleason grading).” Consensus “improves with education and training,” the pair add. To that end, Roche has initiated a global training program for pathologists using the SP142 assay for TNBC. At San Antonio, Roche’s Dennis reported that among 432 pathologists from 58 countries, there was overall agreement of 98.2% in scoring assays.

Rimm commented that such high agreement would not be a surprise if testing took place soon after any such training program.

In an email to Medscape Medical News, Torlakovic encouraged pathologists who wish to practice their skill in interpreting assays, including SP142, to visit CBQAReadout.ca, a testing site. The site, which was founded by Torlakovic and may be one of a kind, offers CME credits and is sponsored by independent pathology organizations, such as CAP-ACP and the Saskatchewan Health Authority, as well as pharmaceutical companies, including Roche.

No Clue

Patient advocate Cowden believes the controversy about PD-L1 testing for atezolizumab is largely unknown among breast cancer patients. She learned about SP142 assay ambiguities in San Antonio, when the Florida Breast Cancer Foundation funded her trip to the meeting and the Alamo Breast Cancer Foundation asked her to write a report on Rimm’s presentation.

Cowden is a member of a Facebook group for stage IV TNBC, which has about 1500 members. She estimates that 75%-80% would be willing to try atezolizumab “no matter what,” meaning they don’t care about PD-L1 positivity being associated with efficacy.

The Facebook group members “know there is a test and if you are positive, there is an immunotherapy for their breast cancer,” said Cowden.

None know that women may be excluded from treatment because of shortcomings with the SP142 test. “They have no clue,” she said.

Rimm and DeMichele have financial ties to Roche and other companies. Dennis is an employee of Roche. Torlakovic has ties to multiple companies, including Roche, for whom she has acted as a paid consultant, grant recipient, and paid lecturer. Gown did not respond to a request for financial disclosures. Cowden reports no relevant financial relationships.

This article first appeared on Medscape.com.

In December, at a major breast cancer conference, some attendees couldn’t find a seat and were told to leave an overcrowded session on immunotherapy for metastatic triple-negative breast cancer (TNBC). They refused, and pushed in to hear what was being said.

The crowd might have been surprised to learn that the main draw of the event, a successful new drug, was not all it might have been for women with the disease, being handicapped by a test that determines who is eligible for it.

“That room was overpacked ― there were five people deep against the wall. ... It was amazing,” said Janice Cowden of Bradenton, Florida. She attended the meeting, the San Antonio Breast Cancer Symposium, as a patient advocate.

Cowden lives with metastatic TNBC, which is known for poor prognoses, aggressiveness, and a lack of targeted treatment options. “Stage IV is a state of desperation. We just want something to work,” she said.

That’s why the conference room was packed – the session was focused on something that had been found to work – the immunotherapy atezolizumab (Tecentriq, Genentech/Roche).

Atezolizumab had recently been conditionally approved for first-line use in advanced TNBC, having been shown to significantly slow disease progression and, in some patients, to possibly improve survival. A pair of medical oncologists reviewed the clinical trial data during the session.

One important point from the trial data was that the benefit was greater in patients whose tumors had the biomarker PD-L1, and so the Food and Drug Administration approval of the drug specified that it should be used only in those patients.

The drug approval was accompanied by approval of a companion diagnostic test used to identify this PD-L1-positive subgroup of patients, the Ventana SP142 Assay (Roche Diagnostics).

At the meeting, pathologist David Rimm, MD, of Yale University, New Haven, Connecticut, discussed the biomarker PD-L1 and the test. Rimm had a subtle but unsettling message about the crucial test: that the SP142 diagnostic assay, when used by increasing numbers of pathologists, resulted in increasing rates of PD-L1 scores that were not concordant.

A related meeting poster, presented the next day with Rimm as senior author, was more explicit and concluded that “more than half of the pathologists in real-world situations may mis- assign” patient scores with SP142 (and another Roche assay) because of wide variability in readouts.

“They’ve made a test that is inadequate – it just doesn’t work. It’s like flipping a coin,” he told Medscape Medical News about Roche’s SP142 assay in everyday practice.

The general problem is not a new one – for some years there have been problems with the use of PD-L1 as a biomarker for immunotherapy and with assays for that biomarker, with many groups questioning both accuracy and reproducibility. But the problems with SP142 are “the most egregious,” said Rimm, who has served as a paid consultant to Roche Diagnostics in the past.

In clinical practice, Rimm’s overall message is that because of the difficulty of reading SP142 assay results, some TNBC patients who were PD-L1-positive would not get the drug, and some who were not positive would get the drug.

Patient advocate Cowden was not worried about overtreatment. She was concerned about patients who “might die without receiving a potentially life-extending treatment.”

In an essay in the Pathologist, Rimm echoed that sentiment about undertreatment (as well as overtreatment) with atezolizumab for breast cancer: “In all cases, the patients are the potential victims, but this appears to be completely under the radar of the hype surrounding this new drug.”
 

Roche Disputes Problems With Assay

Roche, manufacturer of both atezolizumab and the companion diagnostic test, disputes that there is a problem.

The FDA and multiple health authorities worldwide have approved atezolizumab and the companion diagnostic SP142 assay for use in TNBC, points out Eslie Dennis, MD, vice president of medical affairs at Roche Tissue Diagnostics.

“The role of a companion diagnostic assay is to discriminate between responders and non-responders for a specific therapeutic product in a specific indication, with a cut-off based on clinical outcomes,” she wrote in an email to Medscape Medical News.

Data from the pivotal IMpassion130 trial show that the assay was effective at that task. Among the 369 patients in the 902-patient trial whose tumors were ≥1% positive for PD-L1, those treated with atezolizumab (and nab-paclitaxel; n = 185) had a median progression-free survival (PFS) of 7.4 months, vs. 4.8 months among those treated with placebo (and nab-paclitaxel; n = 184) (P < .0001).

“Exploratory analysis showed no [PFS] benefit in PD-L1-negative patients as tested by the SP142 assay [in IMpassion130],” Dennis and three other physicians write in a reply to Rimm in a letter published in July 2019 in the Pathologist.

The same held true for overall survival in exploratory analysis – there was no benefit with atezolizumab among the PD-L1-negative patients, they write.

Notably, overall survival benefit for patients who were PD-L1 positive was about 10 months (at the first interim analysis; at the second analysis, the benefit dropped to 7 months and was not statistically significant).

But Rimm points out that the pivotal trial used only one pathologist in a central lab to determine PD-L1 status, who was undoubtedly an expert with the SP142 assay.

Further, Rimm observes that additional data submitted to the FDA to show that SP142 test results are reproducible outside of the pivotal trial setting were performed with only three pathologists and thus unsurprisingly yielded high rates of agreement – all above 90%.

The data from both of these circumstances are problematic, Rimm said, because in the real world, hundreds of pathologists will score the SP142 assay – all in the context of a busy day reading a variety of other tests for other diseases.

It’s one thing to get an FDA approval for an assay, and it’s another thing to be a reliable, well-functioning assay in the real world, he summarized.

Last year, Roberto Salgado, MD, PhD, a pathologist at the Université Libre de Bruxelles, Belgium, commented that “a positive phase III trial should not be taken as a guarantee that the assay used in the trial can be implemented in daily practice” in an opinion piece in the Pathologist.
 

SP142 Identifies the “Fewest Possible Patients”

The SP142 assay has been shown in multiple studies to have lower sensitivity for PD-L1 than other competing PD-L1 assays, said Rimm, citing examples such as a 2017 study and a 2018 study.

Angela DeMichele, MD, a medical oncologist at the University of Pennsylvania in Philadelphia, agreed and explained what that meant in practical terms for women whose tumors are tested with SP142. “It means that the test is going to identify the fewest possible PD-L1-positive patients [relative to the other available assays],” she said. “It [the SP142 assay] is far from a perfect test for this situation,” added DeMichele, an expert on biomarkers in breast cancer clinical trials.

She said that biomarker tests, like many products of science, tend to become dated with the passage of time, as more is learned about the target and new assays are developed. “Unfortunately, you can’t change assays midstream,” said DeMichele. She has received a grant from Roche and Stand Up to Cancer to study atezolizumab and another drug in a clinical trial among patients with metastatic TNBC who have minimal residual disease.

DeMichele also said that “David Rimm is one of the most knowledgeable people in the world about this issue.”

But DeMichelle also points out the practical: “We’re stuck as clinicians” because regulatory bodies and insurance companies only pay for atezolizumab when the SP142 assay indicates PD-L1 positivity. That’s not the case in Europe, where health authorities do not specify which PD-L1 assay is to be used with atezolizumab for breast cancer, pointed out Belgium’s Salgado last year.
 

Another Level of Complexity

At the immunotherapy session in San Antonio, Rimm discussed the results of a study of 68 TNBC archived cases in which specimens were stained with the SP142 assay at Yale and were distributed via electronic images to 19 pathologists at 14 institutions across the United States for PD-L1 scoring.

The study, coauthored by academics from Iowa, Texas A&M, UC San Diego, Mayo Clinic, Memorial Sloan Kettering, and others, used a novel method to determine the minimum number of evaluators needed to estimate “concordance” or agreement about a test result among large numbers of readers. The consensus/agreement was as high as 80% when eight or fewer pathologists’ scores were compared, but was as low as 40% when results from more than eight pathologists were included, said Rimm.

These are some of the data that led him to declare that using the assay is no better than flipping a coin.

Yes, PD-L1 testing is a challenge, and it has “introduced another level of complexity” for pathologists in reading assays, write experts Emina Torlakovic, MD, University of Saskatchewan, Canada, and Allen Gown, MD, PhenoPath Laboratories, Seattle, in response to Rimm last year.

But there is “poor” consensus among pathologists, they point out, “for many scoring systems that are still clinically applied (such as Gleason grading).” Consensus “improves with education and training,” the pair add. To that end, Roche has initiated a global training program for pathologists using the SP142 assay for TNBC. At San Antonio, Roche’s Dennis reported that among 432 pathologists from 58 countries, there was overall agreement of 98.2% in scoring assays.

Rimm commented that such high agreement would not be a surprise if testing took place soon after any such training program.

In an email to Medscape Medical News, Torlakovic encouraged pathologists who wish to practice their skill in interpreting assays, including SP142, to visit CBQAReadout.ca, a testing site. The site, which was founded by Torlakovic and may be one of a kind, offers CME credits and is sponsored by independent pathology organizations, such as CAP-ACP and the Saskatchewan Health Authority, as well as pharmaceutical companies, including Roche.

No Clue

Patient advocate Cowden believes the controversy about PD-L1 testing for atezolizumab is largely unknown among breast cancer patients. She learned about SP142 assay ambiguities in San Antonio, when the Florida Breast Cancer Foundation funded her trip to the meeting and the Alamo Breast Cancer Foundation asked her to write a report on Rimm’s presentation.

Cowden is a member of a Facebook group for stage IV TNBC, which has about 1500 members. She estimates that 75%-80% would be willing to try atezolizumab “no matter what,” meaning they don’t care about PD-L1 positivity being associated with efficacy.

The Facebook group members “know there is a test and if you are positive, there is an immunotherapy for their breast cancer,” said Cowden.

None know that women may be excluded from treatment because of shortcomings with the SP142 test. “They have no clue,” she said.

Rimm and DeMichele have financial ties to Roche and other companies. Dennis is an employee of Roche. Torlakovic has ties to multiple companies, including Roche, for whom she has acted as a paid consultant, grant recipient, and paid lecturer. Gown did not respond to a request for financial disclosures. Cowden reports no relevant financial relationships.

This article first appeared on Medscape.com.

Urgent care centers may not use optimal medications for the management of acute migraine attacks, according to a study published in the March issue of Headache. Pain and nausea or vomiting associated with migraine may go undertreated, and treatment may not be consistent with American Headache Society (AHS) guidelines for EDs, said Mia T. Minen, MD, of the department of neurology and population health at NYU Langone Health in New York and colleagues.

“Our study findings raise the question as to whether the patients with migraine in the urgent care setting should be managed similarly to the ED, and whether the AHS guidelines for the ED should be revisited and applied to urgent care,” the researchers noted.

Relative to the ED, urgent care centers may provide cost savings and emerge “as a preferred place for treatment for people with migraine, perhaps as they are potentially more quiet medical settings where people with migraine might expeditiously receive care,” the authors said.

Dr. Minen and colleagues conducted a retrospective chart review to assess migraine management at two urgent care centers in New York. They examined the number of urgent care visits for migraine, treatments used, and how closely clinicians followed the AHS recommendations for administration of antiemetic medication and triptans, among other outcomes.

The study population included adults diagnosed with migraine at the NYU Langone Medhattan Urgent Care center between Dec. 1, 2015, and Dec. 1, 2018, or at the NYU Langone Ambulatory Care Urgent Care West Side center between May 1, 2017, and Dec. 1, 2018. Of more than 32,000 urgent care visits during the study period, 78 patients received a migraine diagnosis. Patients with migraine had an average age of 32.5 years, and 79.5% were female. More than half had a documented history of migraine. Two of the patients (2.6%) had been to an emergency department for headache or migraine.

Less than half of the patients who presented with pain (46.6%) were given medication, most commonly ketorolac injection. Most patients (78.2%) received prescriptions, and 25.6% received a triptan prescription. About 60% of patients were told to follow up with a neurologist. In addition, 11.5% revisited urgent care with a migraine or headache or to request a prescription refill.

“Patients in this study appeared to be using the urgent care centers specifically for acute care,” the researchers said. “The patients generally had infrequent headaches and the majority would not have qualified for migraine preventive treatment.”

Although AHS guidelines include three “should offer” medications for acute management of migraine in the ED – intravenous metoclopramide, intravenous prochlorperazine, and subcutaneous sumatriptan – two of the medications, subcutaneous sumatriptan and intravenous prochlorperazine, were not available in the urgent care pharmacy. “Of the level B migraine medications, only metoclopramide IV was in the pharmacy, and only 12.3% was given this at their urgent care visit,” the researchers said. “There was also likely undertreatment of nausea/vomiting; despite 39 patients with recorded nausea or vomiting with their migraine, less than half (46.2%) received an antiemetic at the visit,” including metoclopramide or ondansetron through oral or intravenous administration.

Future studies should look at headache and migraine visits at urgent care centers across the United States, the investigators suggested.

One of the authors of the study (Leslie Miller, MD) is the head of the NYU Langone Health Urgent Care Centers. Dr. Minen has received grant support, honoraria, or travel funds from the National Institutes of Health, the American Academy of Neurology, the American Brain Foundation, the National Multiple Sclerosis Society, the National Headache Foundation, the American Headache Society, Barnard College, and NYU. Dr. Minen is associate editor of Headache.

jremaly@mdedge.com

SOURCE: Minen MT et al. Headache. 2020;60(3):542-52.

Urgent care centers may not use optimal medications for the management of acute migraine attacks, according to a study published in the March issue of Headache. Pain and nausea or vomiting associated with migraine may go undertreated, and treatment may not be consistent with American Headache Society (AHS) guidelines for EDs, said Mia T. Minen, MD, of the department of neurology and population health at NYU Langone Health in New York and colleagues.

“Our study findings raise the question as to whether the patients with migraine in the urgent care setting should be managed similarly to the ED, and whether the AHS guidelines for the ED should be revisited and applied to urgent care,” the researchers noted.

Relative to the ED, urgent care centers may provide cost savings and emerge “as a preferred place for treatment for people with migraine, perhaps as they are potentially more quiet medical settings where people with migraine might expeditiously receive care,” the authors said.

Dr. Minen and colleagues conducted a retrospective chart review to assess migraine management at two urgent care centers in New York. They examined the number of urgent care visits for migraine, treatments used, and how closely clinicians followed the AHS recommendations for administration of antiemetic medication and triptans, among other outcomes.

The study population included adults diagnosed with migraine at the NYU Langone Medhattan Urgent Care center between Dec. 1, 2015, and Dec. 1, 2018, or at the NYU Langone Ambulatory Care Urgent Care West Side center between May 1, 2017, and Dec. 1, 2018. Of more than 32,000 urgent care visits during the study period, 78 patients received a migraine diagnosis. Patients with migraine had an average age of 32.5 years, and 79.5% were female. More than half had a documented history of migraine. Two of the patients (2.6%) had been to an emergency department for headache or migraine.

Less than half of the patients who presented with pain (46.6%) were given medication, most commonly ketorolac injection. Most patients (78.2%) received prescriptions, and 25.6% received a triptan prescription. About 60% of patients were told to follow up with a neurologist. In addition, 11.5% revisited urgent care with a migraine or headache or to request a prescription refill.

“Patients in this study appeared to be using the urgent care centers specifically for acute care,” the researchers said. “The patients generally had infrequent headaches and the majority would not have qualified for migraine preventive treatment.”

Although AHS guidelines include three “should offer” medications for acute management of migraine in the ED – intravenous metoclopramide, intravenous prochlorperazine, and subcutaneous sumatriptan – two of the medications, subcutaneous sumatriptan and intravenous prochlorperazine, were not available in the urgent care pharmacy. “Of the level B migraine medications, only metoclopramide IV was in the pharmacy, and only 12.3% was given this at their urgent care visit,” the researchers said. “There was also likely undertreatment of nausea/vomiting; despite 39 patients with recorded nausea or vomiting with their migraine, less than half (46.2%) received an antiemetic at the visit,” including metoclopramide or ondansetron through oral or intravenous administration.

Future studies should look at headache and migraine visits at urgent care centers across the United States, the investigators suggested.

One of the authors of the study (Leslie Miller, MD) is the head of the NYU Langone Health Urgent Care Centers. Dr. Minen has received grant support, honoraria, or travel funds from the National Institutes of Health, the American Academy of Neurology, the American Brain Foundation, the National Multiple Sclerosis Society, the National Headache Foundation, the American Headache Society, Barnard College, and NYU. Dr. Minen is associate editor of Headache.

jremaly@mdedge.com

SOURCE: Minen MT et al. Headache. 2020;60(3):542-52.

Urgent care centers may not use optimal medications for the management of acute migraine attacks, according to a study published in the March issue of Headache. Pain and nausea or vomiting associated with migraine may go undertreated, and treatment may not be consistent with American Headache Society (AHS) guidelines for EDs, said Mia T. Minen, MD, of the department of neurology and population health at NYU Langone Health in New York and colleagues.

“Our study findings raise the question as to whether the patients with migraine in the urgent care setting should be managed similarly to the ED, and whether the AHS guidelines for the ED should be revisited and applied to urgent care,” the researchers noted.

Relative to the ED, urgent care centers may provide cost savings and emerge “as a preferred place for treatment for people with migraine, perhaps as they are potentially more quiet medical settings where people with migraine might expeditiously receive care,” the authors said.

Dr. Minen and colleagues conducted a retrospective chart review to assess migraine management at two urgent care centers in New York. They examined the number of urgent care visits for migraine, treatments used, and how closely clinicians followed the AHS recommendations for administration of antiemetic medication and triptans, among other outcomes.

The study population included adults diagnosed with migraine at the NYU Langone Medhattan Urgent Care center between Dec. 1, 2015, and Dec. 1, 2018, or at the NYU Langone Ambulatory Care Urgent Care West Side center between May 1, 2017, and Dec. 1, 2018. Of more than 32,000 urgent care visits during the study period, 78 patients received a migraine diagnosis. Patients with migraine had an average age of 32.5 years, and 79.5% were female. More than half had a documented history of migraine. Two of the patients (2.6%) had been to an emergency department for headache or migraine.

Less than half of the patients who presented with pain (46.6%) were given medication, most commonly ketorolac injection. Most patients (78.2%) received prescriptions, and 25.6% received a triptan prescription. About 60% of patients were told to follow up with a neurologist. In addition, 11.5% revisited urgent care with a migraine or headache or to request a prescription refill.

“Patients in this study appeared to be using the urgent care centers specifically for acute care,” the researchers said. “The patients generally had infrequent headaches and the majority would not have qualified for migraine preventive treatment.”

Although AHS guidelines include three “should offer” medications for acute management of migraine in the ED – intravenous metoclopramide, intravenous prochlorperazine, and subcutaneous sumatriptan – two of the medications, subcutaneous sumatriptan and intravenous prochlorperazine, were not available in the urgent care pharmacy. “Of the level B migraine medications, only metoclopramide IV was in the pharmacy, and only 12.3% was given this at their urgent care visit,” the researchers said. “There was also likely undertreatment of nausea/vomiting; despite 39 patients with recorded nausea or vomiting with their migraine, less than half (46.2%) received an antiemetic at the visit,” including metoclopramide or ondansetron through oral or intravenous administration.

Future studies should look at headache and migraine visits at urgent care centers across the United States, the investigators suggested.

One of the authors of the study (Leslie Miller, MD) is the head of the NYU Langone Health Urgent Care Centers. Dr. Minen has received grant support, honoraria, or travel funds from the National Institutes of Health, the American Academy of Neurology, the American Brain Foundation, the National Multiple Sclerosis Society, the National Headache Foundation, the American Headache Society, Barnard College, and NYU. Dr. Minen is associate editor of Headache.

jremaly@mdedge.com

SOURCE: Minen MT et al. Headache. 2020;60(3):542-52.

Eye and vision problems are highly prevalent among patients with Parkinson’s disease and often severe enough to interfere with daily activities, according to the results of a multicenter, cross-sectional cohort study.

“Ophthalmologic symptoms are underreported by patients with Parkinson’s disease and often overlooked by their treating physicians,” noted the investigators, who were led by Carlijn D.J.M. Borm, MD, Parkinson Centre Nijmegen (the Netherlands), Department of Neurology, Donders Institute for Brain, Cognition and Behaviour at Radboud University Medical Centre. “Importantly, intact vision is especially vital for patients with Parkinson’s disease to compensate (through visual guidance) for their common loss of motor automaticity that is caused by basal ganglia dysfunction.”

The investigators studied 848 patients with Parkinson’s disease in the Netherlands and Austria who were recruited by e-mail or in outpatient clinics and 250 age-matched healthy controls drawn from partners and acquaintances, comparing the groups on symptoms assessed with the Visual Impairment in Parkinson’s Disease Questionnaire (VIPD-Q).

Results reported in Neurology showed that 82% of patients with Parkinson’s disease reported at least one ophthalmologic symptom, compared with 48% of age-matched healthy controls (P < .001). Symptoms related to the ocular surface – blurry near vision, a burning or gritty sensation, mucus or particles, and watering of the eyes – were the most common.

Moreover, 68% of patients reported having ophthalmologic symptoms that interfered with daily activities, compared with 35% of healthy controls (P < .001).

The study’s findings suggest “that either Parkinson’s disease itself or its treatment has an effect on ophthalmologic functions beyond the normal aging process,” Dr. Borm and coinvestigators wrote. “The high prevalence of ophthalmologic symptoms and their effect on daily life is striking, and emphasizes the need to address this subject in both research and clinical practice.”

“Patients who report ophthalmologic symptoms need a referral for further evaluation. For those patients who do not volunteer problems themselves, a screening questionnaire such as the VIPD-Q may help with identifying ophthalmologic symptoms in patients with Parkinson’s disease that might otherwise be missed, thereby enabling timely referral and treatment,” they noted.
 

Study details

The study participants were 70 years old, on average, and the patients with Parkinson’s disease had had the disease for a median duration of 7 years. Compared with the healthy control group, the patient group more often reported that they used visual aids (95% vs. 88%; P = .001) and had visited an ophthalmologist (35% vs. 19%; P < .001). The median score on the VIPD-Q, out of a possible 51 points, was 10 among the patients with Parkinson’s disease, compared with 2 among the healthy controls (P < .001).

Patients most commonly reported symptoms related to the ocular surface (63% vs. 24% among controls; P < .001). But they also often reported symptoms in the intraocular domain (54% vs. 25%; P < .001), the oculomotor domain (44% vs. 10%; P < .001), and the optic nerve domain (44% vs. 19%; P < .001). Fully 22% of the patients reported visual hallucinations, compared with just 2% of the healthy controls (P < .001).

As VIPD-Q score increased, so did the likelihood of falls (odds ratio, 1.043; P < .001). In addition, patients with Parkinson’s disease more often reported that ophthalmologic symptoms had a moderate or severe impact on their quality of life (53% vs. 16%; P < .001).

Dr. Borm disclosed no relevant conflicts of interest. The study was funded by the Stichting Parkinson Fonds.
 

Awareness is key to spotting these treatable symptoms

“This study confirms a lot of what we already knew about Parkinson’s disease, but it gives more numbers to it and also the patient’s perspective rather than the doctor’s perspective,” Andrew G. Lee, MD, commented in an interview. “We know that patients with Parkinson’s disease have a lot of ophthalmologic symptoms – probably more than we recognize or ask about in the clinic – and their symptoms predominantly are out of proportion to what we see on exam,” said Dr. Lee, who is chairman of the Department of Ophthalmology at Blanton Eye Institute, Houston Methodist Hospital.

In fact, patients may have normal acuity, normal visual fields, and a normal structural eye exam, yet still report vision problems because of the central neurodegeneration occurring, he noted. “Ophthalmologists cannot rely on just the eye exam when examining patients with Parkinson’s disease. They have to take symptoms into consideration. It’s really important to be aware of how brain disease can affect the eyes symptom-wise, even though the eye exam is normal.”

Administering the questionnaire used in the study is not very difficult but is somewhat time consuming, so most ophthalmologists and neurologists are unlikely to use it, according to Dr. Lee. But knowing common symptoms and asking about them can ensure they are promptly recognized, the first step in addressing them.

“None of the visual complaints in patients with Parkinson’s disease are curable because Parkinson’s disease is not curable and the disease is the underlying major etiology for the problems. However, all of the symptoms have treatments,” he said.

For example, dry eye, caused by decreased blinking, can be treated with drops. Convergence insufficiency, which generates double vision when focusing on nearby objects, can be managed with prisms, exercises, and if needed, eye muscle surgery. Impaired eye movement is best treated with different sets of glasses specific to tasks, such as one pair for reading and one pair for distance. And visual hallucinations can be addressed with changes to existing medications or new medication, or simple reassurance that the hallucinations aren’t harmful.

“It’s important that this kind of study increases awareness in the medical community,” concluded Dr. Lee, who disclosed no relevant conflicts of interest. “The take-home messages are that eye doctors know that these are real complaints, that the eye exam is not going to give the answer, and that all of the symptoms have treatments even though there is no cure.”

SOURCE: Borm CDJM et al. Neurology. 2020 Mar 11. doi: 10.1212/WNL.0000000000009214.

Eye and vision problems are highly prevalent among patients with Parkinson’s disease and often severe enough to interfere with daily activities, according to the results of a multicenter, cross-sectional cohort study.

“Ophthalmologic symptoms are underreported by patients with Parkinson’s disease and often overlooked by their treating physicians,” noted the investigators, who were led by Carlijn D.J.M. Borm, MD, Parkinson Centre Nijmegen (the Netherlands), Department of Neurology, Donders Institute for Brain, Cognition and Behaviour at Radboud University Medical Centre. “Importantly, intact vision is especially vital for patients with Parkinson’s disease to compensate (through visual guidance) for their common loss of motor automaticity that is caused by basal ganglia dysfunction.”

The investigators studied 848 patients with Parkinson’s disease in the Netherlands and Austria who were recruited by e-mail or in outpatient clinics and 250 age-matched healthy controls drawn from partners and acquaintances, comparing the groups on symptoms assessed with the Visual Impairment in Parkinson’s Disease Questionnaire (VIPD-Q).

Results reported in Neurology showed that 82% of patients with Parkinson’s disease reported at least one ophthalmologic symptom, compared with 48% of age-matched healthy controls (P < .001). Symptoms related to the ocular surface – blurry near vision, a burning or gritty sensation, mucus or particles, and watering of the eyes – were the most common.

Moreover, 68% of patients reported having ophthalmologic symptoms that interfered with daily activities, compared with 35% of healthy controls (P < .001).

The study’s findings suggest “that either Parkinson’s disease itself or its treatment has an effect on ophthalmologic functions beyond the normal aging process,” Dr. Borm and coinvestigators wrote. “The high prevalence of ophthalmologic symptoms and their effect on daily life is striking, and emphasizes the need to address this subject in both research and clinical practice.”

“Patients who report ophthalmologic symptoms need a referral for further evaluation. For those patients who do not volunteer problems themselves, a screening questionnaire such as the VIPD-Q may help with identifying ophthalmologic symptoms in patients with Parkinson’s disease that might otherwise be missed, thereby enabling timely referral and treatment,” they noted.
 

Study details

The study participants were 70 years old, on average, and the patients with Parkinson’s disease had had the disease for a median duration of 7 years. Compared with the healthy control group, the patient group more often reported that they used visual aids (95% vs. 88%; P = .001) and had visited an ophthalmologist (35% vs. 19%; P < .001). The median score on the VIPD-Q, out of a possible 51 points, was 10 among the patients with Parkinson’s disease, compared with 2 among the healthy controls (P < .001).

Patients most commonly reported symptoms related to the ocular surface (63% vs. 24% among controls; P < .001). But they also often reported symptoms in the intraocular domain (54% vs. 25%; P < .001), the oculomotor domain (44% vs. 10%; P < .001), and the optic nerve domain (44% vs. 19%; P < .001). Fully 22% of the patients reported visual hallucinations, compared with just 2% of the healthy controls (P < .001).

As VIPD-Q score increased, so did the likelihood of falls (odds ratio, 1.043; P < .001). In addition, patients with Parkinson’s disease more often reported that ophthalmologic symptoms had a moderate or severe impact on their quality of life (53% vs. 16%; P < .001).

Dr. Borm disclosed no relevant conflicts of interest. The study was funded by the Stichting Parkinson Fonds.
 

Awareness is key to spotting these treatable symptoms

“This study confirms a lot of what we already knew about Parkinson’s disease, but it gives more numbers to it and also the patient’s perspective rather than the doctor’s perspective,” Andrew G. Lee, MD, commented in an interview. “We know that patients with Parkinson’s disease have a lot of ophthalmologic symptoms – probably more than we recognize or ask about in the clinic – and their symptoms predominantly are out of proportion to what we see on exam,” said Dr. Lee, who is chairman of the Department of Ophthalmology at Blanton Eye Institute, Houston Methodist Hospital.

In fact, patients may have normal acuity, normal visual fields, and a normal structural eye exam, yet still report vision problems because of the central neurodegeneration occurring, he noted. “Ophthalmologists cannot rely on just the eye exam when examining patients with Parkinson’s disease. They have to take symptoms into consideration. It’s really important to be aware of how brain disease can affect the eyes symptom-wise, even though the eye exam is normal.”

Administering the questionnaire used in the study is not very difficult but is somewhat time consuming, so most ophthalmologists and neurologists are unlikely to use it, according to Dr. Lee. But knowing common symptoms and asking about them can ensure they are promptly recognized, the first step in addressing them.

“None of the visual complaints in patients with Parkinson’s disease are curable because Parkinson’s disease is not curable and the disease is the underlying major etiology for the problems. However, all of the symptoms have treatments,” he said.

For example, dry eye, caused by decreased blinking, can be treated with drops. Convergence insufficiency, which generates double vision when focusing on nearby objects, can be managed with prisms, exercises, and if needed, eye muscle surgery. Impaired eye movement is best treated with different sets of glasses specific to tasks, such as one pair for reading and one pair for distance. And visual hallucinations can be addressed with changes to existing medications or new medication, or simple reassurance that the hallucinations aren’t harmful.

“It’s important that this kind of study increases awareness in the medical community,” concluded Dr. Lee, who disclosed no relevant conflicts of interest. “The take-home messages are that eye doctors know that these are real complaints, that the eye exam is not going to give the answer, and that all of the symptoms have treatments even though there is no cure.”

SOURCE: Borm CDJM et al. Neurology. 2020 Mar 11. doi: 10.1212/WNL.0000000000009214.

Eye and vision problems are highly prevalent among patients with Parkinson’s disease and often severe enough to interfere with daily activities, according to the results of a multicenter, cross-sectional cohort study.

“Ophthalmologic symptoms are underreported by patients with Parkinson’s disease and often overlooked by their treating physicians,” noted the investigators, who were led by Carlijn D.J.M. Borm, MD, Parkinson Centre Nijmegen (the Netherlands), Department of Neurology, Donders Institute for Brain, Cognition and Behaviour at Radboud University Medical Centre. “Importantly, intact vision is especially vital for patients with Parkinson’s disease to compensate (through visual guidance) for their common loss of motor automaticity that is caused by basal ganglia dysfunction.”

The investigators studied 848 patients with Parkinson’s disease in the Netherlands and Austria who were recruited by e-mail or in outpatient clinics and 250 age-matched healthy controls drawn from partners and acquaintances, comparing the groups on symptoms assessed with the Visual Impairment in Parkinson’s Disease Questionnaire (VIPD-Q).

Results reported in Neurology showed that 82% of patients with Parkinson’s disease reported at least one ophthalmologic symptom, compared with 48% of age-matched healthy controls (P < .001). Symptoms related to the ocular surface – blurry near vision, a burning or gritty sensation, mucus or particles, and watering of the eyes – were the most common.

Moreover, 68% of patients reported having ophthalmologic symptoms that interfered with daily activities, compared with 35% of healthy controls (P < .001).

The study’s findings suggest “that either Parkinson’s disease itself or its treatment has an effect on ophthalmologic functions beyond the normal aging process,” Dr. Borm and coinvestigators wrote. “The high prevalence of ophthalmologic symptoms and their effect on daily life is striking, and emphasizes the need to address this subject in both research and clinical practice.”

“Patients who report ophthalmologic symptoms need a referral for further evaluation. For those patients who do not volunteer problems themselves, a screening questionnaire such as the VIPD-Q may help with identifying ophthalmologic symptoms in patients with Parkinson’s disease that might otherwise be missed, thereby enabling timely referral and treatment,” they noted.
 

Study details

The study participants were 70 years old, on average, and the patients with Parkinson’s disease had had the disease for a median duration of 7 years. Compared with the healthy control group, the patient group more often reported that they used visual aids (95% vs. 88%; P = .001) and had visited an ophthalmologist (35% vs. 19%; P < .001). The median score on the VIPD-Q, out of a possible 51 points, was 10 among the patients with Parkinson’s disease, compared with 2 among the healthy controls (P < .001).

Patients most commonly reported symptoms related to the ocular surface (63% vs. 24% among controls; P < .001). But they also often reported symptoms in the intraocular domain (54% vs. 25%; P < .001), the oculomotor domain (44% vs. 10%; P < .001), and the optic nerve domain (44% vs. 19%; P < .001). Fully 22% of the patients reported visual hallucinations, compared with just 2% of the healthy controls (P < .001).

As VIPD-Q score increased, so did the likelihood of falls (odds ratio, 1.043; P < .001). In addition, patients with Parkinson’s disease more often reported that ophthalmologic symptoms had a moderate or severe impact on their quality of life (53% vs. 16%; P < .001).

Dr. Borm disclosed no relevant conflicts of interest. The study was funded by the Stichting Parkinson Fonds.
 

Awareness is key to spotting these treatable symptoms

“This study confirms a lot of what we already knew about Parkinson’s disease, but it gives more numbers to it and also the patient’s perspective rather than the doctor’s perspective,” Andrew G. Lee, MD, commented in an interview. “We know that patients with Parkinson’s disease have a lot of ophthalmologic symptoms – probably more than we recognize or ask about in the clinic – and their symptoms predominantly are out of proportion to what we see on exam,” said Dr. Lee, who is chairman of the Department of Ophthalmology at Blanton Eye Institute, Houston Methodist Hospital.

In fact, patients may have normal acuity, normal visual fields, and a normal structural eye exam, yet still report vision problems because of the central neurodegeneration occurring, he noted. “Ophthalmologists cannot rely on just the eye exam when examining patients with Parkinson’s disease. They have to take symptoms into consideration. It’s really important to be aware of how brain disease can affect the eyes symptom-wise, even though the eye exam is normal.”

Administering the questionnaire used in the study is not very difficult but is somewhat time consuming, so most ophthalmologists and neurologists are unlikely to use it, according to Dr. Lee. But knowing common symptoms and asking about them can ensure they are promptly recognized, the first step in addressing them.

“None of the visual complaints in patients with Parkinson’s disease are curable because Parkinson’s disease is not curable and the disease is the underlying major etiology for the problems. However, all of the symptoms have treatments,” he said.

For example, dry eye, caused by decreased blinking, can be treated with drops. Convergence insufficiency, which generates double vision when focusing on nearby objects, can be managed with prisms, exercises, and if needed, eye muscle surgery. Impaired eye movement is best treated with different sets of glasses specific to tasks, such as one pair for reading and one pair for distance. And visual hallucinations can be addressed with changes to existing medications or new medication, or simple reassurance that the hallucinations aren’t harmful.

“It’s important that this kind of study increases awareness in the medical community,” concluded Dr. Lee, who disclosed no relevant conflicts of interest. “The take-home messages are that eye doctors know that these are real complaints, that the eye exam is not going to give the answer, and that all of the symptoms have treatments even though there is no cure.”

SOURCE: Borm CDJM et al. Neurology. 2020 Mar 11. doi: 10.1212/WNL.0000000000009214.

Current National Comprehensive Cancer Network (NCCN) criteria may prevent genetic testing in “a substantial proportion” of women who carry germline pathogenic variants in breast cancer predisposition genes, according to investigators.

They found that, by expanding NCCN criteria to include germline genetic testing for all women diagnosed with breast cancer at age 65 or younger, the sensitivity of testing for nine well-established breast cancer predisposition genes would improve from 70% to more than 90%. The sensitivity for detection of BRCA1 and BRCA2 only would improve from 87% to greater than 98%.

Siddhartha Yadav, MD, of the Mayo Clinic, Rochester, Minn., and colleagues reported these findings in the Journal of Clinical Oncology.

“In a large unselected series of women with breast cancer, we demonstrate that expanding the NCCN testing criteria to include all women diagnosed with breast cancer at or before the age of 65 years has the potential to improve the sensitivity of germline genetic testing without the need for evaluation of all women with breast cancer,” Dr. Yadav and colleagues wrote.

Robert Pilarski, who was vice-chair of the panel that drew up the NCCN guidelines, said in an interview that the guideline authors tried to achieve a balance.

“We’ve known that NCCN misses cases and indications, but it comes down to whether the goal is to test all women with mutations or to have criteria that are a cost-effective and reasonable compromise to capture as many patients as possible,” said Mr. Pilarski, a licensed genetic counselor at the Ohio State University Wexner Medical Center in Columbus.

Current NCCN criteria for genetic/familial high-risk assessment for breast, ovarian, and pancreatic cancer recommend testing for individuals with blood relatives who have known or likely pathogenic variants, as well as patients with breast cancer diagnosed at age 45 or younger, patients aged 46-50 years with unknown or limited family history, patients with a second breast cancer diagnosed at any age, patients with triple-negative breast cancer diagnosed at age 60 or younger, and patients with breast cancer diagnosed at any age if they are of Ashkenazi Jewish ancestry.

But as Dr. Yadav and colleagues note, two recent studies (J Clin Oncol. 2019 Feb 20;37[6]:453-60; Ann Surg Oncol. 2018 Oct;25[10]:2925-31) suggested that up to 50% of germline pathogenic variants could be missed if testing were based solely on NCCN criteria.

Based on these findings, the American Society of Breast Surgeons issued a consensus guideline on genetic testing for hereditary breast cancer (Ann Surg Oncol. 2019 Oct;26[10]:3025-31), which states that, “genetic testing should be made available to all patients with a personal history of breast cancer.”

“Without question, if your goal is to identify everyone with a mutation, you’d have to test every cancer patient,” Mr. Pilarski said. “At this point, the ASBrS [American Society of Breast Surgeons] are the only group that have proposed that, and a lot of us feel that’s going too far at this point in time, and so the issue becomes what’s reasonable before that, and I think this paper is a great step forward.”
 

Cutting through the confusion

To see whether tweaking the existing guidelines could help clarify the issues surrounding genetic testing for breast cancer, Dr. Yadav and colleagues looked at a cohort of patients from the Mayo Clinic Breast Cancer Study. This prospective registry was open to all women evaluated at the Mayo Clinic Rochester for a first diagnosis of invasive breast cancer or ductal carcinoma in situ from May 2000 through May 2016.

The women were evaluated for germline pathogenic variants in nine breast cancer predisposition genes: ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53.

The researchers found that, of the 3,907 women in the sample, 1,872 (47.9%) would have been recommended for testing under the NCCN criteria, but the remaining 2,035 would not.

Women who met NCCN criteria were significantly more likely to carry a pathogenic variant (9% vs. 3.5%, P less than .001). However, 29.9% of women with pathogenic variants in the nine-gene panel and 13.1% of those with pathogenic variants in BRCA1 or BRCA2 did not qualify for testing by NCCN criteria.

The sensitivity of NCCN criteria was 70% for the nine-gene panel and 87% for BRCA 1 and BRCA 2, with a 53% specificity.

But if the criteria were expanded to include all women age 65 years and younger with a breast cancer diagnosis, the sensitivity for the nine-gene panel would increase to 92.1%, and the sensitivity for BRCA1 and BRCA2 only would climb to greater than 98.1%, with a specificity of approximately 22% for each test combination.

The authors acknowledged that they did not assess the cost-effectiveness of the testing criteria.

This study was supported by grants from the National Institutes of Health and the Breast Cancer Research Foundation. Authors disclosed relationships with Grail, bioTheranostics, Myriad Genetics, and other companies. Mr. Pilarski reported no conflicts of interest.

SOURCE: Yadav S et al. J Clin Oncol. 2020 Mar 3. doi: 10.1200/JCO.19.02190

Current National Comprehensive Cancer Network (NCCN) criteria may prevent genetic testing in “a substantial proportion” of women who carry germline pathogenic variants in breast cancer predisposition genes, according to investigators.

They found that, by expanding NCCN criteria to include germline genetic testing for all women diagnosed with breast cancer at age 65 or younger, the sensitivity of testing for nine well-established breast cancer predisposition genes would improve from 70% to more than 90%. The sensitivity for detection of BRCA1 and BRCA2 only would improve from 87% to greater than 98%.

Siddhartha Yadav, MD, of the Mayo Clinic, Rochester, Minn., and colleagues reported these findings in the Journal of Clinical Oncology.

“In a large unselected series of women with breast cancer, we demonstrate that expanding the NCCN testing criteria to include all women diagnosed with breast cancer at or before the age of 65 years has the potential to improve the sensitivity of germline genetic testing without the need for evaluation of all women with breast cancer,” Dr. Yadav and colleagues wrote.

Robert Pilarski, who was vice-chair of the panel that drew up the NCCN guidelines, said in an interview that the guideline authors tried to achieve a balance.

“We’ve known that NCCN misses cases and indications, but it comes down to whether the goal is to test all women with mutations or to have criteria that are a cost-effective and reasonable compromise to capture as many patients as possible,” said Mr. Pilarski, a licensed genetic counselor at the Ohio State University Wexner Medical Center in Columbus.

Current NCCN criteria for genetic/familial high-risk assessment for breast, ovarian, and pancreatic cancer recommend testing for individuals with blood relatives who have known or likely pathogenic variants, as well as patients with breast cancer diagnosed at age 45 or younger, patients aged 46-50 years with unknown or limited family history, patients with a second breast cancer diagnosed at any age, patients with triple-negative breast cancer diagnosed at age 60 or younger, and patients with breast cancer diagnosed at any age if they are of Ashkenazi Jewish ancestry.

But as Dr. Yadav and colleagues note, two recent studies (J Clin Oncol. 2019 Feb 20;37[6]:453-60; Ann Surg Oncol. 2018 Oct;25[10]:2925-31) suggested that up to 50% of germline pathogenic variants could be missed if testing were based solely on NCCN criteria.

Based on these findings, the American Society of Breast Surgeons issued a consensus guideline on genetic testing for hereditary breast cancer (Ann Surg Oncol. 2019 Oct;26[10]:3025-31), which states that, “genetic testing should be made available to all patients with a personal history of breast cancer.”

“Without question, if your goal is to identify everyone with a mutation, you’d have to test every cancer patient,” Mr. Pilarski said. “At this point, the ASBrS [American Society of Breast Surgeons] are the only group that have proposed that, and a lot of us feel that’s going too far at this point in time, and so the issue becomes what’s reasonable before that, and I think this paper is a great step forward.”
 

Cutting through the confusion

To see whether tweaking the existing guidelines could help clarify the issues surrounding genetic testing for breast cancer, Dr. Yadav and colleagues looked at a cohort of patients from the Mayo Clinic Breast Cancer Study. This prospective registry was open to all women evaluated at the Mayo Clinic Rochester for a first diagnosis of invasive breast cancer or ductal carcinoma in situ from May 2000 through May 2016.

The women were evaluated for germline pathogenic variants in nine breast cancer predisposition genes: ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53.

The researchers found that, of the 3,907 women in the sample, 1,872 (47.9%) would have been recommended for testing under the NCCN criteria, but the remaining 2,035 would not.

Women who met NCCN criteria were significantly more likely to carry a pathogenic variant (9% vs. 3.5%, P less than .001). However, 29.9% of women with pathogenic variants in the nine-gene panel and 13.1% of those with pathogenic variants in BRCA1 or BRCA2 did not qualify for testing by NCCN criteria.

The sensitivity of NCCN criteria was 70% for the nine-gene panel and 87% for BRCA 1 and BRCA 2, with a 53% specificity.

But if the criteria were expanded to include all women age 65 years and younger with a breast cancer diagnosis, the sensitivity for the nine-gene panel would increase to 92.1%, and the sensitivity for BRCA1 and BRCA2 only would climb to greater than 98.1%, with a specificity of approximately 22% for each test combination.

The authors acknowledged that they did not assess the cost-effectiveness of the testing criteria.

This study was supported by grants from the National Institutes of Health and the Breast Cancer Research Foundation. Authors disclosed relationships with Grail, bioTheranostics, Myriad Genetics, and other companies. Mr. Pilarski reported no conflicts of interest.

SOURCE: Yadav S et al. J Clin Oncol. 2020 Mar 3. doi: 10.1200/JCO.19.02190

Current National Comprehensive Cancer Network (NCCN) criteria may prevent genetic testing in “a substantial proportion” of women who carry germline pathogenic variants in breast cancer predisposition genes, according to investigators.

They found that, by expanding NCCN criteria to include germline genetic testing for all women diagnosed with breast cancer at age 65 or younger, the sensitivity of testing for nine well-established breast cancer predisposition genes would improve from 70% to more than 90%. The sensitivity for detection of BRCA1 and BRCA2 only would improve from 87% to greater than 98%.

Siddhartha Yadav, MD, of the Mayo Clinic, Rochester, Minn., and colleagues reported these findings in the Journal of Clinical Oncology.

“In a large unselected series of women with breast cancer, we demonstrate that expanding the NCCN testing criteria to include all women diagnosed with breast cancer at or before the age of 65 years has the potential to improve the sensitivity of germline genetic testing without the need for evaluation of all women with breast cancer,” Dr. Yadav and colleagues wrote.

Robert Pilarski, who was vice-chair of the panel that drew up the NCCN guidelines, said in an interview that the guideline authors tried to achieve a balance.

“We’ve known that NCCN misses cases and indications, but it comes down to whether the goal is to test all women with mutations or to have criteria that are a cost-effective and reasonable compromise to capture as many patients as possible,” said Mr. Pilarski, a licensed genetic counselor at the Ohio State University Wexner Medical Center in Columbus.

Current NCCN criteria for genetic/familial high-risk assessment for breast, ovarian, and pancreatic cancer recommend testing for individuals with blood relatives who have known or likely pathogenic variants, as well as patients with breast cancer diagnosed at age 45 or younger, patients aged 46-50 years with unknown or limited family history, patients with a second breast cancer diagnosed at any age, patients with triple-negative breast cancer diagnosed at age 60 or younger, and patients with breast cancer diagnosed at any age if they are of Ashkenazi Jewish ancestry.

But as Dr. Yadav and colleagues note, two recent studies (J Clin Oncol. 2019 Feb 20;37[6]:453-60; Ann Surg Oncol. 2018 Oct;25[10]:2925-31) suggested that up to 50% of germline pathogenic variants could be missed if testing were based solely on NCCN criteria.

Based on these findings, the American Society of Breast Surgeons issued a consensus guideline on genetic testing for hereditary breast cancer (Ann Surg Oncol. 2019 Oct;26[10]:3025-31), which states that, “genetic testing should be made available to all patients with a personal history of breast cancer.”

“Without question, if your goal is to identify everyone with a mutation, you’d have to test every cancer patient,” Mr. Pilarski said. “At this point, the ASBrS [American Society of Breast Surgeons] are the only group that have proposed that, and a lot of us feel that’s going too far at this point in time, and so the issue becomes what’s reasonable before that, and I think this paper is a great step forward.”
 

Cutting through the confusion

To see whether tweaking the existing guidelines could help clarify the issues surrounding genetic testing for breast cancer, Dr. Yadav and colleagues looked at a cohort of patients from the Mayo Clinic Breast Cancer Study. This prospective registry was open to all women evaluated at the Mayo Clinic Rochester for a first diagnosis of invasive breast cancer or ductal carcinoma in situ from May 2000 through May 2016.

The women were evaluated for germline pathogenic variants in nine breast cancer predisposition genes: ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53.

The researchers found that, of the 3,907 women in the sample, 1,872 (47.9%) would have been recommended for testing under the NCCN criteria, but the remaining 2,035 would not.

Women who met NCCN criteria were significantly more likely to carry a pathogenic variant (9% vs. 3.5%, P less than .001). However, 29.9% of women with pathogenic variants in the nine-gene panel and 13.1% of those with pathogenic variants in BRCA1 or BRCA2 did not qualify for testing by NCCN criteria.

The sensitivity of NCCN criteria was 70% for the nine-gene panel and 87% for BRCA 1 and BRCA 2, with a 53% specificity.

But if the criteria were expanded to include all women age 65 years and younger with a breast cancer diagnosis, the sensitivity for the nine-gene panel would increase to 92.1%, and the sensitivity for BRCA1 and BRCA2 only would climb to greater than 98.1%, with a specificity of approximately 22% for each test combination.

The authors acknowledged that they did not assess the cost-effectiveness of the testing criteria.

This study was supported by grants from the National Institutes of Health and the Breast Cancer Research Foundation. Authors disclosed relationships with Grail, bioTheranostics, Myriad Genetics, and other companies. Mr. Pilarski reported no conflicts of interest.

SOURCE: Yadav S et al. J Clin Oncol. 2020 Mar 3. doi: 10.1200/JCO.19.02190

In this edition of “Applying research to practice,” I highlight a study revealing real-world information about the clinical care of breast cancer patients with deleterious germline mutations.

While germline testing among breast cancer patients is becoming more commonplace, it isn’t clear how test results influence patient care. To gain some insight, Allison W. Kurian, MD, of Stanford (Calif.) University, and colleagues analyzed data on 20,568 women with stage 0-III breast cancer from the Surveillance, Epidemiology, and End Results (SEER) registries of Georgia and California (JAMA Oncol. 2020 Feb 6. doi: 10.1001/jamaoncol.2019.6400).

The researchers aimed to determine whether women with mutations in breast cancer–associated genes (BRCA1/2 or others) received guideline-concordant care to the same degree as women who lacked deleterious mutations. The authors evaluated guideline concordance with respect to three treatment modalities: surgery (bilateral vs. unilateral mastectomy in women who were eligible for unilateral surgery), radiotherapy after lumpectomy (for women aged less than 70 years with hormonally responsive, ErbB2-negative, stage I cancers), and chemotherapy (among women eligible for consideration of chemotherapy omission)

In alignment with guidelines, many clinicians correctly used genetic test results to guide surgical decisions. For example, 61.7% of women with BRCA mutations underwent bilateral mastectomy, compared with 24.3% who were mutation negative (odds ratio, 5.52). For other pathogenic variants (ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, and TP53), the rate of bilateral mastectomy was still elevated, albeit to a lesser degree (OR, 2.41).

In discord with guidelines, women with BRCA mutations were 78% less likely to receive radiotherapy after lumpectomy (OR, 0.22) and 76% more likely to receive chemotherapy for early-stage, hormone-positive disease (OR, 1.76), suggesting possible trends in under- and overtreatment, respectively. Chemotherapy utilization rates among mutation carriers and noncarriers became more similar after adjustment for clinical and demographic factors.

There are limits on the granularity of the SEER database, such that, if a patient had a mastectomy a year or more after lumpectomy in an effort to avoid radiotherapy, the database would not have reflected that. Clinical factors could have appropriately influenced chemotherapy receipt among patients with mutations, but those additional factors (including patient preference) would not be included in the SEER data.

The authors concluded that research should be conducted to confirm the results of this retrospective, population-based cohort analysis, in an effort to understand the decision-making process and consequences for long-term outcome.
 

How these findings should influence practice

With every new development, there are challenges – some expected, some unanticipated.

It is now feasible to obtain multigene panel testing reasonably inexpensively. There are concerns about undertesting of patients on the basis of family history alone. And some major professional organizations have endorsed routine gene panel testing for all breast cancer patients.

As a consequence of these factors, genetic test results are routinely available to clinicians who may lack formal training in clinical genetics. Whether these results influence the receipt of evidence-based clinical care is uncertain.

The information published by Dr. Kurian and colleagues is inherently limited by the methodology of a SEER database review. Among other limitations, as the authors comment:

• The genetic test results could have arrived after treatment decisions were made.
• Treatment delivered more than a year after diagnosis would not have been captured.
• There was selection of patients for genetic testing.
• There were few patients with particular germline mutations other than BRCA1/2 on whom to judge whether treatment was guideline concordant.
• The rationale for the treatment choices made by physicians and patients was not available.
• Impact of treatment choices on survival for carriers of deleterious mutations is uncertain.

Nonetheless, these data suggest a need to redouble efforts to educate patients, their family members, and health care professionals about evidence-based guidelines for care and the rationale for those recommendations.

Careful, prospective monitoring of any resultant differences in treatment outcome in patients treated with guideline-concordant and nonconcordant care is needed. When treatment choices appear to systematically deviate from published guidelines with no obvious rationale, it is a wake-up call for all of us.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

In this edition of “Applying research to practice,” I highlight a study revealing real-world information about the clinical care of breast cancer patients with deleterious germline mutations.

While germline testing among breast cancer patients is becoming more commonplace, it isn’t clear how test results influence patient care. To gain some insight, Allison W. Kurian, MD, of Stanford (Calif.) University, and colleagues analyzed data on 20,568 women with stage 0-III breast cancer from the Surveillance, Epidemiology, and End Results (SEER) registries of Georgia and California (JAMA Oncol. 2020 Feb 6. doi: 10.1001/jamaoncol.2019.6400).

The researchers aimed to determine whether women with mutations in breast cancer–associated genes (BRCA1/2 or others) received guideline-concordant care to the same degree as women who lacked deleterious mutations. The authors evaluated guideline concordance with respect to three treatment modalities: surgery (bilateral vs. unilateral mastectomy in women who were eligible for unilateral surgery), radiotherapy after lumpectomy (for women aged less than 70 years with hormonally responsive, ErbB2-negative, stage I cancers), and chemotherapy (among women eligible for consideration of chemotherapy omission)

In alignment with guidelines, many clinicians correctly used genetic test results to guide surgical decisions. For example, 61.7% of women with BRCA mutations underwent bilateral mastectomy, compared with 24.3% who were mutation negative (odds ratio, 5.52). For other pathogenic variants (ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, and TP53), the rate of bilateral mastectomy was still elevated, albeit to a lesser degree (OR, 2.41).

In discord with guidelines, women with BRCA mutations were 78% less likely to receive radiotherapy after lumpectomy (OR, 0.22) and 76% more likely to receive chemotherapy for early-stage, hormone-positive disease (OR, 1.76), suggesting possible trends in under- and overtreatment, respectively. Chemotherapy utilization rates among mutation carriers and noncarriers became more similar after adjustment for clinical and demographic factors.

There are limits on the granularity of the SEER database, such that, if a patient had a mastectomy a year or more after lumpectomy in an effort to avoid radiotherapy, the database would not have reflected that. Clinical factors could have appropriately influenced chemotherapy receipt among patients with mutations, but those additional factors (including patient preference) would not be included in the SEER data.

The authors concluded that research should be conducted to confirm the results of this retrospective, population-based cohort analysis, in an effort to understand the decision-making process and consequences for long-term outcome.
 

How these findings should influence practice

With every new development, there are challenges – some expected, some unanticipated.

It is now feasible to obtain multigene panel testing reasonably inexpensively. There are concerns about undertesting of patients on the basis of family history alone. And some major professional organizations have endorsed routine gene panel testing for all breast cancer patients.

As a consequence of these factors, genetic test results are routinely available to clinicians who may lack formal training in clinical genetics. Whether these results influence the receipt of evidence-based clinical care is uncertain.

The information published by Dr. Kurian and colleagues is inherently limited by the methodology of a SEER database review. Among other limitations, as the authors comment:

• The genetic test results could have arrived after treatment decisions were made.
• Treatment delivered more than a year after diagnosis would not have been captured.
• There was selection of patients for genetic testing.
• There were few patients with particular germline mutations other than BRCA1/2 on whom to judge whether treatment was guideline concordant.
• The rationale for the treatment choices made by physicians and patients was not available.
• Impact of treatment choices on survival for carriers of deleterious mutations is uncertain.

Nonetheless, these data suggest a need to redouble efforts to educate patients, their family members, and health care professionals about evidence-based guidelines for care and the rationale for those recommendations.

Careful, prospective monitoring of any resultant differences in treatment outcome in patients treated with guideline-concordant and nonconcordant care is needed. When treatment choices appear to systematically deviate from published guidelines with no obvious rationale, it is a wake-up call for all of us.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.

In this edition of “Applying research to practice,” I highlight a study revealing real-world information about the clinical care of breast cancer patients with deleterious germline mutations.

While germline testing among breast cancer patients is becoming more commonplace, it isn’t clear how test results influence patient care. To gain some insight, Allison W. Kurian, MD, of Stanford (Calif.) University, and colleagues analyzed data on 20,568 women with stage 0-III breast cancer from the Surveillance, Epidemiology, and End Results (SEER) registries of Georgia and California (JAMA Oncol. 2020 Feb 6. doi: 10.1001/jamaoncol.2019.6400).

The researchers aimed to determine whether women with mutations in breast cancer–associated genes (BRCA1/2 or others) received guideline-concordant care to the same degree as women who lacked deleterious mutations. The authors evaluated guideline concordance with respect to three treatment modalities: surgery (bilateral vs. unilateral mastectomy in women who were eligible for unilateral surgery), radiotherapy after lumpectomy (for women aged less than 70 years with hormonally responsive, ErbB2-negative, stage I cancers), and chemotherapy (among women eligible for consideration of chemotherapy omission)

In alignment with guidelines, many clinicians correctly used genetic test results to guide surgical decisions. For example, 61.7% of women with BRCA mutations underwent bilateral mastectomy, compared with 24.3% who were mutation negative (odds ratio, 5.52). For other pathogenic variants (ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, and TP53), the rate of bilateral mastectomy was still elevated, albeit to a lesser degree (OR, 2.41).

In discord with guidelines, women with BRCA mutations were 78% less likely to receive radiotherapy after lumpectomy (OR, 0.22) and 76% more likely to receive chemotherapy for early-stage, hormone-positive disease (OR, 1.76), suggesting possible trends in under- and overtreatment, respectively. Chemotherapy utilization rates among mutation carriers and noncarriers became more similar after adjustment for clinical and demographic factors.

There are limits on the granularity of the SEER database, such that, if a patient had a mastectomy a year or more after lumpectomy in an effort to avoid radiotherapy, the database would not have reflected that. Clinical factors could have appropriately influenced chemotherapy receipt among patients with mutations, but those additional factors (including patient preference) would not be included in the SEER data.

The authors concluded that research should be conducted to confirm the results of this retrospective, population-based cohort analysis, in an effort to understand the decision-making process and consequences for long-term outcome.
 

How these findings should influence practice

With every new development, there are challenges – some expected, some unanticipated.

It is now feasible to obtain multigene panel testing reasonably inexpensively. There are concerns about undertesting of patients on the basis of family history alone. And some major professional organizations have endorsed routine gene panel testing for all breast cancer patients.

As a consequence of these factors, genetic test results are routinely available to clinicians who may lack formal training in clinical genetics. Whether these results influence the receipt of evidence-based clinical care is uncertain.

The information published by Dr. Kurian and colleagues is inherently limited by the methodology of a SEER database review. Among other limitations, as the authors comment:

• The genetic test results could have arrived after treatment decisions were made.
• Treatment delivered more than a year after diagnosis would not have been captured.
• There was selection of patients for genetic testing.
• There were few patients with particular germline mutations other than BRCA1/2 on whom to judge whether treatment was guideline concordant.
• The rationale for the treatment choices made by physicians and patients was not available.
• Impact of treatment choices on survival for carriers of deleterious mutations is uncertain.

Nonetheless, these data suggest a need to redouble efforts to educate patients, their family members, and health care professionals about evidence-based guidelines for care and the rationale for those recommendations.

Careful, prospective monitoring of any resultant differences in treatment outcome in patients treated with guideline-concordant and nonconcordant care is needed. When treatment choices appear to systematically deviate from published guidelines with no obvious rationale, it is a wake-up call for all of us.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations.