User login
FDA approves first oral somatostatin analog for acromegaly
who previously responded to and tolerated octreotide or lanreotide injections.
“People living with acromegaly experience many challenges associated with injectable therapies and are in need of new treatment options,” Jill Sisco, president of Acromegaly Community, a patient support group, said in a Chiasma press release.
“The entire acromegaly community has long awaited oral therapeutic options and it is gratifying to see that the FDA has now approved the first oral somatostatin analog (SSA) therapy with the potential to make a significant impact in the lives of people with acromegaly and their caregivers,” she added.
Acromegaly, a rare, chronic disease usually caused by a benign pituitary tumor that leads to excess production of growth hormone and insulin-like growth factor-1 (IGF-1) hormone, can be cured through the successful surgical removal of the pituitary tumor. However, management of the disease remains a lifelong challenge for many who must rely on chronic injections.
The new oral formulation of octreotide is the first and only oral somatostatin analog approved by the FDA.
The approval was based on the results of the 9-month, phase 3 pivotal CHIASMA OPTIMAL clinical trial, involving 56 adults with acromegaly controlled by injectable SSAs.
The patients, who were randomized 1:1 to octreotide capsules or placebo, were dose-titrated from 40 mg/day up to a maximum of 80 mg/day, equaling two capsules in the morning and two in the evening.
The study met its primary endpoint. Overall, 58% of patients taking octreotide maintained IGF-1 response compared with 19% of those on placebo at the end of 9 months (P = .008), according to the average of the last two IGF-1 levels that were 1 times or less the upper limit of normal, assessed at weeks 34 and 36.
The trial also met its secondary endpoints, which included the proportion of patients who maintain growth hormone response at week 36 compared with screening; time to loss of response; and proportion of patients requiring reversion to prior treatment.
Safety data were favorable. Adverse reactions to the drug, detailed in the prescribing information, include cholelithiasis and associated complications; hyperglycemia and hypoglycemia; thyroid function abnormalities; cardiac function abnormalities; decreased vitamin B12 levels, and abnormal Schilling’s test results.
Results from the clinical trial “are encouraging for patients with acromegaly,” the study’s principal investigator, Susan Samson, MD, PhD, of Baylor College of Medicine, Houston, said in the Chiasma statement.
“Based on data from the CHIASMA OPTIMAL trial showing patients on therapy being able to maintain mean IGF-1 levels within the normal range at the end of treatment, I believe oral octreotide capsules hold meaningful promise for patients with this disease and will address a long-standing unmet treatment need,” she added.
Chiasma reports that it expects Mycapssa to be available in the fourth quarter of 2020, pending FDA approval of a planned manufacturing supplement to the approved new drug application.
The company further plans to provide patient support services including assistance with insurance providers and specialty pharmacies and support in incorporating treatment into patients’ daily routines.
Despite effective biochemical control of growth hormone, many patients with acromegaly continue to suffer symptoms, mainly because of comorbidities, so it is important that these are also adequately treated, a consensus group concluded earlier this year.
The CHIASMA OPTIMAL trial was funded by Chiasma.
A version of this article originally appeared on Medscape.com.
who previously responded to and tolerated octreotide or lanreotide injections.
“People living with acromegaly experience many challenges associated with injectable therapies and are in need of new treatment options,” Jill Sisco, president of Acromegaly Community, a patient support group, said in a Chiasma press release.
“The entire acromegaly community has long awaited oral therapeutic options and it is gratifying to see that the FDA has now approved the first oral somatostatin analog (SSA) therapy with the potential to make a significant impact in the lives of people with acromegaly and their caregivers,” she added.
Acromegaly, a rare, chronic disease usually caused by a benign pituitary tumor that leads to excess production of growth hormone and insulin-like growth factor-1 (IGF-1) hormone, can be cured through the successful surgical removal of the pituitary tumor. However, management of the disease remains a lifelong challenge for many who must rely on chronic injections.
The new oral formulation of octreotide is the first and only oral somatostatin analog approved by the FDA.
The approval was based on the results of the 9-month, phase 3 pivotal CHIASMA OPTIMAL clinical trial, involving 56 adults with acromegaly controlled by injectable SSAs.
The patients, who were randomized 1:1 to octreotide capsules or placebo, were dose-titrated from 40 mg/day up to a maximum of 80 mg/day, equaling two capsules in the morning and two in the evening.
The study met its primary endpoint. Overall, 58% of patients taking octreotide maintained IGF-1 response compared with 19% of those on placebo at the end of 9 months (P = .008), according to the average of the last two IGF-1 levels that were 1 times or less the upper limit of normal, assessed at weeks 34 and 36.
The trial also met its secondary endpoints, which included the proportion of patients who maintain growth hormone response at week 36 compared with screening; time to loss of response; and proportion of patients requiring reversion to prior treatment.
Safety data were favorable. Adverse reactions to the drug, detailed in the prescribing information, include cholelithiasis and associated complications; hyperglycemia and hypoglycemia; thyroid function abnormalities; cardiac function abnormalities; decreased vitamin B12 levels, and abnormal Schilling’s test results.
Results from the clinical trial “are encouraging for patients with acromegaly,” the study’s principal investigator, Susan Samson, MD, PhD, of Baylor College of Medicine, Houston, said in the Chiasma statement.
“Based on data from the CHIASMA OPTIMAL trial showing patients on therapy being able to maintain mean IGF-1 levels within the normal range at the end of treatment, I believe oral octreotide capsules hold meaningful promise for patients with this disease and will address a long-standing unmet treatment need,” she added.
Chiasma reports that it expects Mycapssa to be available in the fourth quarter of 2020, pending FDA approval of a planned manufacturing supplement to the approved new drug application.
The company further plans to provide patient support services including assistance with insurance providers and specialty pharmacies and support in incorporating treatment into patients’ daily routines.
Despite effective biochemical control of growth hormone, many patients with acromegaly continue to suffer symptoms, mainly because of comorbidities, so it is important that these are also adequately treated, a consensus group concluded earlier this year.
The CHIASMA OPTIMAL trial was funded by Chiasma.
A version of this article originally appeared on Medscape.com.
who previously responded to and tolerated octreotide or lanreotide injections.
“People living with acromegaly experience many challenges associated with injectable therapies and are in need of new treatment options,” Jill Sisco, president of Acromegaly Community, a patient support group, said in a Chiasma press release.
“The entire acromegaly community has long awaited oral therapeutic options and it is gratifying to see that the FDA has now approved the first oral somatostatin analog (SSA) therapy with the potential to make a significant impact in the lives of people with acromegaly and their caregivers,” she added.
Acromegaly, a rare, chronic disease usually caused by a benign pituitary tumor that leads to excess production of growth hormone and insulin-like growth factor-1 (IGF-1) hormone, can be cured through the successful surgical removal of the pituitary tumor. However, management of the disease remains a lifelong challenge for many who must rely on chronic injections.
The new oral formulation of octreotide is the first and only oral somatostatin analog approved by the FDA.
The approval was based on the results of the 9-month, phase 3 pivotal CHIASMA OPTIMAL clinical trial, involving 56 adults with acromegaly controlled by injectable SSAs.
The patients, who were randomized 1:1 to octreotide capsules or placebo, were dose-titrated from 40 mg/day up to a maximum of 80 mg/day, equaling two capsules in the morning and two in the evening.
The study met its primary endpoint. Overall, 58% of patients taking octreotide maintained IGF-1 response compared with 19% of those on placebo at the end of 9 months (P = .008), according to the average of the last two IGF-1 levels that were 1 times or less the upper limit of normal, assessed at weeks 34 and 36.
The trial also met its secondary endpoints, which included the proportion of patients who maintain growth hormone response at week 36 compared with screening; time to loss of response; and proportion of patients requiring reversion to prior treatment.
Safety data were favorable. Adverse reactions to the drug, detailed in the prescribing information, include cholelithiasis and associated complications; hyperglycemia and hypoglycemia; thyroid function abnormalities; cardiac function abnormalities; decreased vitamin B12 levels, and abnormal Schilling’s test results.
Results from the clinical trial “are encouraging for patients with acromegaly,” the study’s principal investigator, Susan Samson, MD, PhD, of Baylor College of Medicine, Houston, said in the Chiasma statement.
“Based on data from the CHIASMA OPTIMAL trial showing patients on therapy being able to maintain mean IGF-1 levels within the normal range at the end of treatment, I believe oral octreotide capsules hold meaningful promise for patients with this disease and will address a long-standing unmet treatment need,” she added.
Chiasma reports that it expects Mycapssa to be available in the fourth quarter of 2020, pending FDA approval of a planned manufacturing supplement to the approved new drug application.
The company further plans to provide patient support services including assistance with insurance providers and specialty pharmacies and support in incorporating treatment into patients’ daily routines.
Despite effective biochemical control of growth hormone, many patients with acromegaly continue to suffer symptoms, mainly because of comorbidities, so it is important that these are also adequately treated, a consensus group concluded earlier this year.
The CHIASMA OPTIMAL trial was funded by Chiasma.
A version of this article originally appeared on Medscape.com.
FDA approves new treatment for Dravet syndrome
Dravet syndrome is a rare childhood-onset epilepsy characterized by frequent, drug-resistant convulsive seizures that may contribute to intellectual disability and impairments in motor control, behavior, and cognition, as well as an increased risk of sudden unexpected death in epilepsy (SUDEP).
Dravet syndrome takes a “tremendous toll on both patients and their families. Fintepla offers an additional effective treatment option for the treatment of seizures associated with Dravet syndrome,” Billy Dunn, MD, director, Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a news release.
The FDA approved fenfluramine for Dravet syndrome based on the results of two randomized, double-blind, placebo-controlled phase 3 trials involving children ages 2 to 18 years with Dravet syndrome.
In both studies, children treated with fenfluramine experienced significantly greater reductions in the frequency of convulsive seizures than did their peers who received placebo. These reductions occurred within 3 to 4 weeks, and remained generally consistent over the 14- to 15-week treatment periods, the FDA said.
“There remains a huge unmet need for the many Dravet syndrome patients who continue to experience frequent severe seizures even while taking one or more of the currently available antiseizure medications,” Joseph Sullivan, MD, who worked on the fenfluramine for Dravet syndrome studies, said in a news release.
Given the “profound reductions” in convulsive seizure frequency seen in the clinical trials, combined with the “ongoing, robust safety monitoring,” fenfluramine offers “an extremely important treatment option for Dravet syndrome patients,” said Dr. Sullivan, director of the Pediatric Epilepsy Center of Excellence at the University of California San Francisco (UCSF) Benioff Children’s Hospital.
Fenfluramine is an anorectic agent that was used to treat obesity until it was removed from the market in 1997 over reports of increased risk of valvular heart disease when prescribed in higher doses and most often when prescribed with phentermine. The combination of the two drugs was known as fen-phen.
In the clinical trials of Dravet syndrome, the most common adverse reactions were decreased appetite; somnolence, sedation, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; increased blood pressure; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; fall; and status epilepticus.
The Fintepla label has a boxed warning stating that the drug is associated with valvular heart disease (VHD) and pulmonary arterial hypertension (PAH). Due to these risks, patients must undergo echocardiography before treatment, every 6 months during treatment, and once 3 to 6 months after treatment is stopped.
If signs of VHD, PAH, or other cardiac abnormalities are present, clinicians should weigh the benefits and risks of continuing treatment with Fintepla, the FDA said.
Fintepla is available only through a risk evaluation and mitigation strategy (REMS) program, which requires physicians who prescribe the drug and pharmacies that dispense it to be certified in the Fintepla REMS and that patients be enrolled in the program.
As part of the REMS requirements, prescribers and patients must adhere to the required cardiac monitoring to receive the drug.
Fintepla will be available to certified prescribers in the United States in July. Zogenix is launching Zogenix Central, a comprehensive support service that will provide ongoing product assistance to patients, caregivers, and their medical teams. Further information is available online.
This article first appeared on Medscape.com.
Dravet syndrome is a rare childhood-onset epilepsy characterized by frequent, drug-resistant convulsive seizures that may contribute to intellectual disability and impairments in motor control, behavior, and cognition, as well as an increased risk of sudden unexpected death in epilepsy (SUDEP).
Dravet syndrome takes a “tremendous toll on both patients and their families. Fintepla offers an additional effective treatment option for the treatment of seizures associated with Dravet syndrome,” Billy Dunn, MD, director, Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a news release.
The FDA approved fenfluramine for Dravet syndrome based on the results of two randomized, double-blind, placebo-controlled phase 3 trials involving children ages 2 to 18 years with Dravet syndrome.
In both studies, children treated with fenfluramine experienced significantly greater reductions in the frequency of convulsive seizures than did their peers who received placebo. These reductions occurred within 3 to 4 weeks, and remained generally consistent over the 14- to 15-week treatment periods, the FDA said.
“There remains a huge unmet need for the many Dravet syndrome patients who continue to experience frequent severe seizures even while taking one or more of the currently available antiseizure medications,” Joseph Sullivan, MD, who worked on the fenfluramine for Dravet syndrome studies, said in a news release.
Given the “profound reductions” in convulsive seizure frequency seen in the clinical trials, combined with the “ongoing, robust safety monitoring,” fenfluramine offers “an extremely important treatment option for Dravet syndrome patients,” said Dr. Sullivan, director of the Pediatric Epilepsy Center of Excellence at the University of California San Francisco (UCSF) Benioff Children’s Hospital.
Fenfluramine is an anorectic agent that was used to treat obesity until it was removed from the market in 1997 over reports of increased risk of valvular heart disease when prescribed in higher doses and most often when prescribed with phentermine. The combination of the two drugs was known as fen-phen.
In the clinical trials of Dravet syndrome, the most common adverse reactions were decreased appetite; somnolence, sedation, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; increased blood pressure; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; fall; and status epilepticus.
The Fintepla label has a boxed warning stating that the drug is associated with valvular heart disease (VHD) and pulmonary arterial hypertension (PAH). Due to these risks, patients must undergo echocardiography before treatment, every 6 months during treatment, and once 3 to 6 months after treatment is stopped.
If signs of VHD, PAH, or other cardiac abnormalities are present, clinicians should weigh the benefits and risks of continuing treatment with Fintepla, the FDA said.
Fintepla is available only through a risk evaluation and mitigation strategy (REMS) program, which requires physicians who prescribe the drug and pharmacies that dispense it to be certified in the Fintepla REMS and that patients be enrolled in the program.
As part of the REMS requirements, prescribers and patients must adhere to the required cardiac monitoring to receive the drug.
Fintepla will be available to certified prescribers in the United States in July. Zogenix is launching Zogenix Central, a comprehensive support service that will provide ongoing product assistance to patients, caregivers, and their medical teams. Further information is available online.
This article first appeared on Medscape.com.
Dravet syndrome is a rare childhood-onset epilepsy characterized by frequent, drug-resistant convulsive seizures that may contribute to intellectual disability and impairments in motor control, behavior, and cognition, as well as an increased risk of sudden unexpected death in epilepsy (SUDEP).
Dravet syndrome takes a “tremendous toll on both patients and their families. Fintepla offers an additional effective treatment option for the treatment of seizures associated with Dravet syndrome,” Billy Dunn, MD, director, Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a news release.
The FDA approved fenfluramine for Dravet syndrome based on the results of two randomized, double-blind, placebo-controlled phase 3 trials involving children ages 2 to 18 years with Dravet syndrome.
In both studies, children treated with fenfluramine experienced significantly greater reductions in the frequency of convulsive seizures than did their peers who received placebo. These reductions occurred within 3 to 4 weeks, and remained generally consistent over the 14- to 15-week treatment periods, the FDA said.
“There remains a huge unmet need for the many Dravet syndrome patients who continue to experience frequent severe seizures even while taking one or more of the currently available antiseizure medications,” Joseph Sullivan, MD, who worked on the fenfluramine for Dravet syndrome studies, said in a news release.
Given the “profound reductions” in convulsive seizure frequency seen in the clinical trials, combined with the “ongoing, robust safety monitoring,” fenfluramine offers “an extremely important treatment option for Dravet syndrome patients,” said Dr. Sullivan, director of the Pediatric Epilepsy Center of Excellence at the University of California San Francisco (UCSF) Benioff Children’s Hospital.
Fenfluramine is an anorectic agent that was used to treat obesity until it was removed from the market in 1997 over reports of increased risk of valvular heart disease when prescribed in higher doses and most often when prescribed with phentermine. The combination of the two drugs was known as fen-phen.
In the clinical trials of Dravet syndrome, the most common adverse reactions were decreased appetite; somnolence, sedation, lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue, malaise, asthenia; ataxia, balance disorder, gait disturbance; increased blood pressure; drooling, salivary hypersecretion; pyrexia; upper respiratory tract infection; vomiting; decreased weight; fall; and status epilepticus.
The Fintepla label has a boxed warning stating that the drug is associated with valvular heart disease (VHD) and pulmonary arterial hypertension (PAH). Due to these risks, patients must undergo echocardiography before treatment, every 6 months during treatment, and once 3 to 6 months after treatment is stopped.
If signs of VHD, PAH, or other cardiac abnormalities are present, clinicians should weigh the benefits and risks of continuing treatment with Fintepla, the FDA said.
Fintepla is available only through a risk evaluation and mitigation strategy (REMS) program, which requires physicians who prescribe the drug and pharmacies that dispense it to be certified in the Fintepla REMS and that patients be enrolled in the program.
As part of the REMS requirements, prescribers and patients must adhere to the required cardiac monitoring to receive the drug.
Fintepla will be available to certified prescribers in the United States in July. Zogenix is launching Zogenix Central, a comprehensive support service that will provide ongoing product assistance to patients, caregivers, and their medical teams. Further information is available online.
This article first appeared on Medscape.com.
First reported U.S. case of COVID-19 linked to Guillain-Barré syndrome
further supporting a link between the virus and neurologic complications, including GBS.
Physicians in China reported the first case of COVID-19 that initially presented as acute GBS. The patient was a 61-year-old woman returning home from Wuhan during the pandemic.
Subsequently, physicians in Italy reported five cases of GBS in association with COVID-19.
The first U.S. case is described in the June issue of the Journal of Clinical Neuromuscular Disease.
Like cases from China and Italy, the U.S. patient’s symptoms of GBS reportedly occurred within days of being infected with SARS-CoV-2. “This onset is similar to a case report of acute Zika virus infection with concurrent GBS suggesting a parainfectious complication,” first author Sandeep Rana, MD, and colleagues noted.
The 54-year-old man was transferred to Allegheny General Hospital after developing ascending limb weakness and numbness that followed symptoms of a respiratory infection. Two weeks earlier, he initially developed rhinorrhea, odynophagia, fevers, chills, and night sweats. The man reported that his wife had tested positive for COVID-19 and that his symptoms started soon after her illness. The man also tested positive for COVID-19.
His deficits were characterized by quadriparesis and areflexia, burning dysesthesias, mild ophthalmoparesis, and dysautonomia. He did not have the loss of smell and taste documented in other COVID-19 patients. He briefly required mechanical ventilation and was successfully weaned after receiving a course of intravenous immunoglobulin.
Compared with other cases reported in the literature, the unique clinical features in the U.S. case are urinary retention secondary to dysautonomia and ocular symptoms of diplopia. These highlight the variability in the clinical presentation of GBS associated with COVID-19, the researchers noted.
They added that, with the Pittsburgh patient, electrophysiological findings were typical of demyelinating polyneuropathy seen in patients with GBS. The case series from Italy suggests that axonal variants could be as common in COVID-19–associated GBS.
“Although the number of documented cases internationally is notably small to date, it’s not completely surprising that a COVID-19 diagnosis may lead to a patient developing GBS. The increase of inflammation and inflammatory cells caused by the infection may trigger an irregular immune response that leads to the hallmark symptoms of this neurological disorder,” Dr. Rana said in a news release.
“Since GBS can significantly affect the respiratory system and other vital organs being pushed into overdrive during a COVID-19 immune response, it will be critically important to further investigate and understand this potential connection,” he added.
A version of this article originally appeared on Medscape.com.
further supporting a link between the virus and neurologic complications, including GBS.
Physicians in China reported the first case of COVID-19 that initially presented as acute GBS. The patient was a 61-year-old woman returning home from Wuhan during the pandemic.
Subsequently, physicians in Italy reported five cases of GBS in association with COVID-19.
The first U.S. case is described in the June issue of the Journal of Clinical Neuromuscular Disease.
Like cases from China and Italy, the U.S. patient’s symptoms of GBS reportedly occurred within days of being infected with SARS-CoV-2. “This onset is similar to a case report of acute Zika virus infection with concurrent GBS suggesting a parainfectious complication,” first author Sandeep Rana, MD, and colleagues noted.
The 54-year-old man was transferred to Allegheny General Hospital after developing ascending limb weakness and numbness that followed symptoms of a respiratory infection. Two weeks earlier, he initially developed rhinorrhea, odynophagia, fevers, chills, and night sweats. The man reported that his wife had tested positive for COVID-19 and that his symptoms started soon after her illness. The man also tested positive for COVID-19.
His deficits were characterized by quadriparesis and areflexia, burning dysesthesias, mild ophthalmoparesis, and dysautonomia. He did not have the loss of smell and taste documented in other COVID-19 patients. He briefly required mechanical ventilation and was successfully weaned after receiving a course of intravenous immunoglobulin.
Compared with other cases reported in the literature, the unique clinical features in the U.S. case are urinary retention secondary to dysautonomia and ocular symptoms of diplopia. These highlight the variability in the clinical presentation of GBS associated with COVID-19, the researchers noted.
They added that, with the Pittsburgh patient, electrophysiological findings were typical of demyelinating polyneuropathy seen in patients with GBS. The case series from Italy suggests that axonal variants could be as common in COVID-19–associated GBS.
“Although the number of documented cases internationally is notably small to date, it’s not completely surprising that a COVID-19 diagnosis may lead to a patient developing GBS. The increase of inflammation and inflammatory cells caused by the infection may trigger an irregular immune response that leads to the hallmark symptoms of this neurological disorder,” Dr. Rana said in a news release.
“Since GBS can significantly affect the respiratory system and other vital organs being pushed into overdrive during a COVID-19 immune response, it will be critically important to further investigate and understand this potential connection,” he added.
A version of this article originally appeared on Medscape.com.
further supporting a link between the virus and neurologic complications, including GBS.
Physicians in China reported the first case of COVID-19 that initially presented as acute GBS. The patient was a 61-year-old woman returning home from Wuhan during the pandemic.
Subsequently, physicians in Italy reported five cases of GBS in association with COVID-19.
The first U.S. case is described in the June issue of the Journal of Clinical Neuromuscular Disease.
Like cases from China and Italy, the U.S. patient’s symptoms of GBS reportedly occurred within days of being infected with SARS-CoV-2. “This onset is similar to a case report of acute Zika virus infection with concurrent GBS suggesting a parainfectious complication,” first author Sandeep Rana, MD, and colleagues noted.
The 54-year-old man was transferred to Allegheny General Hospital after developing ascending limb weakness and numbness that followed symptoms of a respiratory infection. Two weeks earlier, he initially developed rhinorrhea, odynophagia, fevers, chills, and night sweats. The man reported that his wife had tested positive for COVID-19 and that his symptoms started soon after her illness. The man also tested positive for COVID-19.
His deficits were characterized by quadriparesis and areflexia, burning dysesthesias, mild ophthalmoparesis, and dysautonomia. He did not have the loss of smell and taste documented in other COVID-19 patients. He briefly required mechanical ventilation and was successfully weaned after receiving a course of intravenous immunoglobulin.
Compared with other cases reported in the literature, the unique clinical features in the U.S. case are urinary retention secondary to dysautonomia and ocular symptoms of diplopia. These highlight the variability in the clinical presentation of GBS associated with COVID-19, the researchers noted.
They added that, with the Pittsburgh patient, electrophysiological findings were typical of demyelinating polyneuropathy seen in patients with GBS. The case series from Italy suggests that axonal variants could be as common in COVID-19–associated GBS.
“Although the number of documented cases internationally is notably small to date, it’s not completely surprising that a COVID-19 diagnosis may lead to a patient developing GBS. The increase of inflammation and inflammatory cells caused by the infection may trigger an irregular immune response that leads to the hallmark symptoms of this neurological disorder,” Dr. Rana said in a news release.
“Since GBS can significantly affect the respiratory system and other vital organs being pushed into overdrive during a COVID-19 immune response, it will be critically important to further investigate and understand this potential connection,” he added.
A version of this article originally appeared on Medscape.com.
Be vigilant for scleroderma renal crisis
Scleroderma renal crisis is often the most challenging type of scleroderma emergency to identify promptly, according to Francesco Boin, MD, professor of medicine and director of the scleroderma center at the University of California, San Francisco.
“Fortunately, it’s not a frequent event. But it’s severe enough that all rheumatologists should be aware of it,” he said at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
Atypical presentations occur in 30%
Scleroderma renal crisis (SRC) occurs in 5%-10% of scleroderma patients. A vexing feature of this emergency is that not uncommonly it actually precedes the diagnosis of scleroderma. Indeed, 20% of patients with SRC present with sine scleroderma – that is, they have no skin disease and their renal crisis is their first symptom of scleroderma. In contrast, critical digital ischemia – the most common scleroderma emergency – is invariably preceded by worsening episodes of Raynaud’s, and impending intestinal pseudo-obstruction – also among the most common scleroderma emergencies – is heralded by an established history of dysmotility, loss of appetite, abdominal bloating, small intestinal bacterial overgrowth, and bowel distension.
While sine SRC often poses a formidable diagnostic challenge, SRC occurs most often in patients with early, rapidly progressing diffuse scleroderma skin disease. Indeed, the median duration of scleroderma when SRC strikes is just 8 months. The use of glucocorticoids at 15 mg or more per day, or at lower doses for a lengthy period, is an independent risk factor for SRC. Detection of anti–RNA polymerase III antibodies warrants increased vigilance, since 60% of patients with SRC are anti–RNA polymerase III antibody positive. Other autoantibodies are not a risk factor. Neither is preexisting hypertension nor a high baseline serum creatinine.
The classic textbook presentation of SRC is abrupt onset of blood pressures greater than 20 mm Hg above normal for that individual, along with sudden renal failure; a climbing creatinine; proteinuria; and expressions of malignant hypertension such as pulmonary edema, new-onset heart failure, encephalopathy, and/or development of a thrombotic microangiopathy.
Notably, however, 30% of individuals with SRC don’t fit this picture at all. They may present with abrupt-onset severe hypertension but no evidence of renal failure, at least early on. Or they may have sudden renal failure without a hypertensive crisis. Alternatively, they may have no signs of malignant hypertension, just an asymptomatic pericardial effusion or mild arrhythmias.
“Also, the thrombotic microangiopathy can be present without the other features of scleroderma renal crisis, so no renal failure or hypertensive emergency. Be aware of the possibility of atypical presentations, and always suspect this unfolding problem in the right individuals,” the rheumatologist urged.
Anyone with scleroderma who presents with new-onset hypertension needs to begin keeping a careful home blood pressure diary. If the blood pressure shoots up, or symptoms of malignant hypertension develop, or laboratory monitoring reveals evidence of thrombotic microangiopathy, the patient should immediately go to the ED because these events are often followed by accelerated progression to renal crisis.
Inpatient management of SRC is critical. “In the hospital we can monitor renal function in a more refined way, we can manage the malignant hypertension, and early on, hospitalization provides the opportunity to do a renal biopsy. I always consider doing this early. The pathologist often pushes back, but I think it’s relevant. It confirms the diagnosis. We’ve had patients where we were surprised: We thought it was scleroderma renal crisis, but instead they had interstitial nephritis or glomerulonephritis. Most important, biopsy has major prognostic implications: You can measure the extent of damage and therefore have a sense of whether the patient will be able to recover renal function,” Dr. Boin explained.
Prognosis and predictors
Outcome of SRC is often poor: the 1-year mortality is 20%-30%, with a 5-year mortality of 30%-50%. Normotensive SRC with renal crisis, which accounts for about 10% of all cases of SRC, is particularly serious in its implication, with a 1-year mortality of 60%. Half of patients with SRC require hemodialysis, and only one-quarter of them recover spontaneous renal function.
Predictors of worse outcome include older age at onset of SRC, male gender, a serum creatinine level above 3 mg/dL at presentation, incomplete blood pressure control within the first 3 days of the crisis, and normotensive SRC. Use of an ACE inhibitor prior to SRC is also an independent predictor of poor outcome, possibly because by keeping the blood pressure under control the medication blunts recognition of the unfolding renal crisis.
“This is why experts don’t recommend prophylactic ACE inhibitors in patients who are at risk for SRC,” according to Dr. Boin.
He reported having no financial conflicts regarding his presentation.
Scleroderma renal crisis is often the most challenging type of scleroderma emergency to identify promptly, according to Francesco Boin, MD, professor of medicine and director of the scleroderma center at the University of California, San Francisco.
“Fortunately, it’s not a frequent event. But it’s severe enough that all rheumatologists should be aware of it,” he said at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
Atypical presentations occur in 30%
Scleroderma renal crisis (SRC) occurs in 5%-10% of scleroderma patients. A vexing feature of this emergency is that not uncommonly it actually precedes the diagnosis of scleroderma. Indeed, 20% of patients with SRC present with sine scleroderma – that is, they have no skin disease and their renal crisis is their first symptom of scleroderma. In contrast, critical digital ischemia – the most common scleroderma emergency – is invariably preceded by worsening episodes of Raynaud’s, and impending intestinal pseudo-obstruction – also among the most common scleroderma emergencies – is heralded by an established history of dysmotility, loss of appetite, abdominal bloating, small intestinal bacterial overgrowth, and bowel distension.
While sine SRC often poses a formidable diagnostic challenge, SRC occurs most often in patients with early, rapidly progressing diffuse scleroderma skin disease. Indeed, the median duration of scleroderma when SRC strikes is just 8 months. The use of glucocorticoids at 15 mg or more per day, or at lower doses for a lengthy period, is an independent risk factor for SRC. Detection of anti–RNA polymerase III antibodies warrants increased vigilance, since 60% of patients with SRC are anti–RNA polymerase III antibody positive. Other autoantibodies are not a risk factor. Neither is preexisting hypertension nor a high baseline serum creatinine.
The classic textbook presentation of SRC is abrupt onset of blood pressures greater than 20 mm Hg above normal for that individual, along with sudden renal failure; a climbing creatinine; proteinuria; and expressions of malignant hypertension such as pulmonary edema, new-onset heart failure, encephalopathy, and/or development of a thrombotic microangiopathy.
Notably, however, 30% of individuals with SRC don’t fit this picture at all. They may present with abrupt-onset severe hypertension but no evidence of renal failure, at least early on. Or they may have sudden renal failure without a hypertensive crisis. Alternatively, they may have no signs of malignant hypertension, just an asymptomatic pericardial effusion or mild arrhythmias.
“Also, the thrombotic microangiopathy can be present without the other features of scleroderma renal crisis, so no renal failure or hypertensive emergency. Be aware of the possibility of atypical presentations, and always suspect this unfolding problem in the right individuals,” the rheumatologist urged.
Anyone with scleroderma who presents with new-onset hypertension needs to begin keeping a careful home blood pressure diary. If the blood pressure shoots up, or symptoms of malignant hypertension develop, or laboratory monitoring reveals evidence of thrombotic microangiopathy, the patient should immediately go to the ED because these events are often followed by accelerated progression to renal crisis.
Inpatient management of SRC is critical. “In the hospital we can monitor renal function in a more refined way, we can manage the malignant hypertension, and early on, hospitalization provides the opportunity to do a renal biopsy. I always consider doing this early. The pathologist often pushes back, but I think it’s relevant. It confirms the diagnosis. We’ve had patients where we were surprised: We thought it was scleroderma renal crisis, but instead they had interstitial nephritis or glomerulonephritis. Most important, biopsy has major prognostic implications: You can measure the extent of damage and therefore have a sense of whether the patient will be able to recover renal function,” Dr. Boin explained.
Prognosis and predictors
Outcome of SRC is often poor: the 1-year mortality is 20%-30%, with a 5-year mortality of 30%-50%. Normotensive SRC with renal crisis, which accounts for about 10% of all cases of SRC, is particularly serious in its implication, with a 1-year mortality of 60%. Half of patients with SRC require hemodialysis, and only one-quarter of them recover spontaneous renal function.
Predictors of worse outcome include older age at onset of SRC, male gender, a serum creatinine level above 3 mg/dL at presentation, incomplete blood pressure control within the first 3 days of the crisis, and normotensive SRC. Use of an ACE inhibitor prior to SRC is also an independent predictor of poor outcome, possibly because by keeping the blood pressure under control the medication blunts recognition of the unfolding renal crisis.
“This is why experts don’t recommend prophylactic ACE inhibitors in patients who are at risk for SRC,” according to Dr. Boin.
He reported having no financial conflicts regarding his presentation.
Scleroderma renal crisis is often the most challenging type of scleroderma emergency to identify promptly, according to Francesco Boin, MD, professor of medicine and director of the scleroderma center at the University of California, San Francisco.
“Fortunately, it’s not a frequent event. But it’s severe enough that all rheumatologists should be aware of it,” he said at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.
Atypical presentations occur in 30%
Scleroderma renal crisis (SRC) occurs in 5%-10% of scleroderma patients. A vexing feature of this emergency is that not uncommonly it actually precedes the diagnosis of scleroderma. Indeed, 20% of patients with SRC present with sine scleroderma – that is, they have no skin disease and their renal crisis is their first symptom of scleroderma. In contrast, critical digital ischemia – the most common scleroderma emergency – is invariably preceded by worsening episodes of Raynaud’s, and impending intestinal pseudo-obstruction – also among the most common scleroderma emergencies – is heralded by an established history of dysmotility, loss of appetite, abdominal bloating, small intestinal bacterial overgrowth, and bowel distension.
While sine SRC often poses a formidable diagnostic challenge, SRC occurs most often in patients with early, rapidly progressing diffuse scleroderma skin disease. Indeed, the median duration of scleroderma when SRC strikes is just 8 months. The use of glucocorticoids at 15 mg or more per day, or at lower doses for a lengthy period, is an independent risk factor for SRC. Detection of anti–RNA polymerase III antibodies warrants increased vigilance, since 60% of patients with SRC are anti–RNA polymerase III antibody positive. Other autoantibodies are not a risk factor. Neither is preexisting hypertension nor a high baseline serum creatinine.
The classic textbook presentation of SRC is abrupt onset of blood pressures greater than 20 mm Hg above normal for that individual, along with sudden renal failure; a climbing creatinine; proteinuria; and expressions of malignant hypertension such as pulmonary edema, new-onset heart failure, encephalopathy, and/or development of a thrombotic microangiopathy.
Notably, however, 30% of individuals with SRC don’t fit this picture at all. They may present with abrupt-onset severe hypertension but no evidence of renal failure, at least early on. Or they may have sudden renal failure without a hypertensive crisis. Alternatively, they may have no signs of malignant hypertension, just an asymptomatic pericardial effusion or mild arrhythmias.
“Also, the thrombotic microangiopathy can be present without the other features of scleroderma renal crisis, so no renal failure or hypertensive emergency. Be aware of the possibility of atypical presentations, and always suspect this unfolding problem in the right individuals,” the rheumatologist urged.
Anyone with scleroderma who presents with new-onset hypertension needs to begin keeping a careful home blood pressure diary. If the blood pressure shoots up, or symptoms of malignant hypertension develop, or laboratory monitoring reveals evidence of thrombotic microangiopathy, the patient should immediately go to the ED because these events are often followed by accelerated progression to renal crisis.
Inpatient management of SRC is critical. “In the hospital we can monitor renal function in a more refined way, we can manage the malignant hypertension, and early on, hospitalization provides the opportunity to do a renal biopsy. I always consider doing this early. The pathologist often pushes back, but I think it’s relevant. It confirms the diagnosis. We’ve had patients where we were surprised: We thought it was scleroderma renal crisis, but instead they had interstitial nephritis or glomerulonephritis. Most important, biopsy has major prognostic implications: You can measure the extent of damage and therefore have a sense of whether the patient will be able to recover renal function,” Dr. Boin explained.
Prognosis and predictors
Outcome of SRC is often poor: the 1-year mortality is 20%-30%, with a 5-year mortality of 30%-50%. Normotensive SRC with renal crisis, which accounts for about 10% of all cases of SRC, is particularly serious in its implication, with a 1-year mortality of 60%. Half of patients with SRC require hemodialysis, and only one-quarter of them recover spontaneous renal function.
Predictors of worse outcome include older age at onset of SRC, male gender, a serum creatinine level above 3 mg/dL at presentation, incomplete blood pressure control within the first 3 days of the crisis, and normotensive SRC. Use of an ACE inhibitor prior to SRC is also an independent predictor of poor outcome, possibly because by keeping the blood pressure under control the medication blunts recognition of the unfolding renal crisis.
“This is why experts don’t recommend prophylactic ACE inhibitors in patients who are at risk for SRC,” according to Dr. Boin.
He reported having no financial conflicts regarding his presentation.
FROM SOTA 2020
Can an app guide cancer treatment decisions during the pandemic?
Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic.
In early April, as the COVID-19 surge was bearing down on New York City, those treatment decisions were “a juggling act every single day,” Jonathan Yang, MD, PhD, a radiation oncologist from New York’s Memorial Sloan Kettering Cancer Center, told Medscape Medical News.
Eventually, a glut of guidelines, recommendations, and expert opinions aimed at helping oncologists emerged. The tools help navigate the complicated risk-benefit analysis of their patient’s risk of infection by SARS-CoV-2 and delaying therapy.
Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help?
Three-Tier Systems Are Not Very Sophisticated
OncCOVID, a free tool that was launched May 26 by the University of Michigan, allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care.
Combining these personal details with data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry and the National Cancer Database, the Michigan app then estimates a patient’s 5- or 10-year survival with immediate vs delayed treatment and weighs that against their risk for COVID-19 using data from the Johns Hopkins Coronavirus Resource Center.
“We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine.
Spratt explained that almost every organization, professional society, and government has created something like a three-tier system. Tier 1 represents urgent cases and patients who need immediate treatment. For tier 2, treatment can be delayed weeks or a month, and with tier 3, it can be delayed until the pandemic is over or it’s deemed safe.
“[This system] sounds good at first glance, but in cancer, we’re always talking about personalized medicine, and it’s mind-blowing that these tier systems are only based on urgency and prognosis,” he told Medscape Medical News.
Spratt offered an example. Consider a patient with a very aggressive brain tumor ― that patient is in tier 1 and should undergo treatment immediately. But will the treatment actually help? And how helpful would the procedure be if, say, the patient is 80 years old and, if infected, would have a 30% to 50% chance of dying from the coronavirus?
“If the model says this guy has a 5% harm and this one has 30% harm, you can use that to help prioritize,” summarized Spratt.
The app can generate risk estimates for patients living anywhere in the world and has already been accessed by people from 37 countries. However, Spratt cautions that it is primarily “designed and calibrated for the US.
“The estimates are based on very large US registries, and though it’s probably somewhat similar across much of the world, there’s probably certain cancer types that are more region specific ― especially something like stomach cancer or certain types of head and neck cancer in parts of Asia, for example,” he said.
Although the app’s COVID-19 data are specific to the county level in the United States, elsewhere in the world, it is only country specific.
“We’re using the best data we have for coronavirus, but everyone knows we still have large data gaps,” he acknowledged.
How Accurate?
Asked to comment on the app, Richard Bleicher, MD, leader of the Breast Cancer Program at Fox Chase Cancer Center, Philadelphia, praised the effort and the goal but had some concerns.
“Several questions arise, most important of which is, How accurate is this, and how has this been validated, if at all ― especially as it is too soon to see the outcomes of patients affected in this pandemic?” he told Medscape Medical News.
“We are imposing delays on a broad scale because of the coronavirus, and we are getting continuously changing data as we test more patients. But both situations are novel and may not be accurately represented by the data being pulled, because the datasets use patients from a few years ago, and confounders in these datasets may not apply to this situation,” Bleicher continued.
Although acknowledging the “value in delineating the risk of dying from cancer vs the risk of dying from the SARS-CoV-2 pandemic,” Bleicher urged caution in using the tool to make individual patient decisions.
“We need to remember that the best of modeling ... can be wildly inaccurate and needs to be validated using patients having the circumstances in question. ... This won’t be possible until long after the pandemic is completed, and so the model’s accuracy remains unknown.”
That sentiment was echoed by Giampaolo Bianchini, MD, head of the Breast Cancer Group, Department of Medical Oncology, Ospedale San Raffaele, in Milan, Italy.
“Arbitrarily postponing and modifying treatment strategies including surgery, radiation therapy, and medical therapy without properly balancing the risk/benefit ratio may lead to significantly worse cancer-related outcomes, which largely exceed the actual risks for COVID,” he wrote in an email.
“The OncCOVID app is a remarkable attempt to fill the gap between perception and estimation,” he said. The app provides side by side the COVID-19 risk estimation and the consequences of arbitrary deviation from the standard of care, observed Bianchini.
However, he pointed out weaknesses, including the fact that the “data generated in literature are not always of high quality and do not take into consideration relevant characteristics of the disease and treatment benefit. It should for sure be used, but then also interpreted with caution.”
Another Italian group responded more positively.
“In our opinion, it could be a useful tool for clinicians,” wrote colleagues Alessio Cortelinni and Giampiero Porzio, both medical oncologists at San Salvatore Hospital and the University of L’Aquila, in Italy. “This Web app might assist clinicians in balancing the risk/benefit ratio of being treated and/or access to the outpatient cancer center for each kind of patient (both early and advanced stages), in order to make a more tailored counseling,” they wrote in an email. “Importantly, the Web app might help those clinicians who work ‘alone,’ in peripheral centers, without resources, colleagues, and multidisciplinary tumor boards on whom they can rely.”
Bleicher, who was involved in the COVID-19 Breast Cancer Consortium’s recommendations for prioritizing breast cancer treatment, summarized that the app “may end up being close or accurate, but we won’t know except in hindsight.”
This article first appeared on Medscape.com.
Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic.
In early April, as the COVID-19 surge was bearing down on New York City, those treatment decisions were “a juggling act every single day,” Jonathan Yang, MD, PhD, a radiation oncologist from New York’s Memorial Sloan Kettering Cancer Center, told Medscape Medical News.
Eventually, a glut of guidelines, recommendations, and expert opinions aimed at helping oncologists emerged. The tools help navigate the complicated risk-benefit analysis of their patient’s risk of infection by SARS-CoV-2 and delaying therapy.
Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help?
Three-Tier Systems Are Not Very Sophisticated
OncCOVID, a free tool that was launched May 26 by the University of Michigan, allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care.
Combining these personal details with data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry and the National Cancer Database, the Michigan app then estimates a patient’s 5- or 10-year survival with immediate vs delayed treatment and weighs that against their risk for COVID-19 using data from the Johns Hopkins Coronavirus Resource Center.
“We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine.
Spratt explained that almost every organization, professional society, and government has created something like a three-tier system. Tier 1 represents urgent cases and patients who need immediate treatment. For tier 2, treatment can be delayed weeks or a month, and with tier 3, it can be delayed until the pandemic is over or it’s deemed safe.
“[This system] sounds good at first glance, but in cancer, we’re always talking about personalized medicine, and it’s mind-blowing that these tier systems are only based on urgency and prognosis,” he told Medscape Medical News.
Spratt offered an example. Consider a patient with a very aggressive brain tumor ― that patient is in tier 1 and should undergo treatment immediately. But will the treatment actually help? And how helpful would the procedure be if, say, the patient is 80 years old and, if infected, would have a 30% to 50% chance of dying from the coronavirus?
“If the model says this guy has a 5% harm and this one has 30% harm, you can use that to help prioritize,” summarized Spratt.
The app can generate risk estimates for patients living anywhere in the world and has already been accessed by people from 37 countries. However, Spratt cautions that it is primarily “designed and calibrated for the US.
“The estimates are based on very large US registries, and though it’s probably somewhat similar across much of the world, there’s probably certain cancer types that are more region specific ― especially something like stomach cancer or certain types of head and neck cancer in parts of Asia, for example,” he said.
Although the app’s COVID-19 data are specific to the county level in the United States, elsewhere in the world, it is only country specific.
“We’re using the best data we have for coronavirus, but everyone knows we still have large data gaps,” he acknowledged.
How Accurate?
Asked to comment on the app, Richard Bleicher, MD, leader of the Breast Cancer Program at Fox Chase Cancer Center, Philadelphia, praised the effort and the goal but had some concerns.
“Several questions arise, most important of which is, How accurate is this, and how has this been validated, if at all ― especially as it is too soon to see the outcomes of patients affected in this pandemic?” he told Medscape Medical News.
“We are imposing delays on a broad scale because of the coronavirus, and we are getting continuously changing data as we test more patients. But both situations are novel and may not be accurately represented by the data being pulled, because the datasets use patients from a few years ago, and confounders in these datasets may not apply to this situation,” Bleicher continued.
Although acknowledging the “value in delineating the risk of dying from cancer vs the risk of dying from the SARS-CoV-2 pandemic,” Bleicher urged caution in using the tool to make individual patient decisions.
“We need to remember that the best of modeling ... can be wildly inaccurate and needs to be validated using patients having the circumstances in question. ... This won’t be possible until long after the pandemic is completed, and so the model’s accuracy remains unknown.”
That sentiment was echoed by Giampaolo Bianchini, MD, head of the Breast Cancer Group, Department of Medical Oncology, Ospedale San Raffaele, in Milan, Italy.
“Arbitrarily postponing and modifying treatment strategies including surgery, radiation therapy, and medical therapy without properly balancing the risk/benefit ratio may lead to significantly worse cancer-related outcomes, which largely exceed the actual risks for COVID,” he wrote in an email.
“The OncCOVID app is a remarkable attempt to fill the gap between perception and estimation,” he said. The app provides side by side the COVID-19 risk estimation and the consequences of arbitrary deviation from the standard of care, observed Bianchini.
However, he pointed out weaknesses, including the fact that the “data generated in literature are not always of high quality and do not take into consideration relevant characteristics of the disease and treatment benefit. It should for sure be used, but then also interpreted with caution.”
Another Italian group responded more positively.
“In our opinion, it could be a useful tool for clinicians,” wrote colleagues Alessio Cortelinni and Giampiero Porzio, both medical oncologists at San Salvatore Hospital and the University of L’Aquila, in Italy. “This Web app might assist clinicians in balancing the risk/benefit ratio of being treated and/or access to the outpatient cancer center for each kind of patient (both early and advanced stages), in order to make a more tailored counseling,” they wrote in an email. “Importantly, the Web app might help those clinicians who work ‘alone,’ in peripheral centers, without resources, colleagues, and multidisciplinary tumor boards on whom they can rely.”
Bleicher, who was involved in the COVID-19 Breast Cancer Consortium’s recommendations for prioritizing breast cancer treatment, summarized that the app “may end up being close or accurate, but we won’t know except in hindsight.”
This article first appeared on Medscape.com.
Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic.
In early April, as the COVID-19 surge was bearing down on New York City, those treatment decisions were “a juggling act every single day,” Jonathan Yang, MD, PhD, a radiation oncologist from New York’s Memorial Sloan Kettering Cancer Center, told Medscape Medical News.
Eventually, a glut of guidelines, recommendations, and expert opinions aimed at helping oncologists emerged. The tools help navigate the complicated risk-benefit analysis of their patient’s risk of infection by SARS-CoV-2 and delaying therapy.
Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help?
Three-Tier Systems Are Not Very Sophisticated
OncCOVID, a free tool that was launched May 26 by the University of Michigan, allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care.
Combining these personal details with data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry and the National Cancer Database, the Michigan app then estimates a patient’s 5- or 10-year survival with immediate vs delayed treatment and weighs that against their risk for COVID-19 using data from the Johns Hopkins Coronavirus Resource Center.
“We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine.
Spratt explained that almost every organization, professional society, and government has created something like a three-tier system. Tier 1 represents urgent cases and patients who need immediate treatment. For tier 2, treatment can be delayed weeks or a month, and with tier 3, it can be delayed until the pandemic is over or it’s deemed safe.
“[This system] sounds good at first glance, but in cancer, we’re always talking about personalized medicine, and it’s mind-blowing that these tier systems are only based on urgency and prognosis,” he told Medscape Medical News.
Spratt offered an example. Consider a patient with a very aggressive brain tumor ― that patient is in tier 1 and should undergo treatment immediately. But will the treatment actually help? And how helpful would the procedure be if, say, the patient is 80 years old and, if infected, would have a 30% to 50% chance of dying from the coronavirus?
“If the model says this guy has a 5% harm and this one has 30% harm, you can use that to help prioritize,” summarized Spratt.
The app can generate risk estimates for patients living anywhere in the world and has already been accessed by people from 37 countries. However, Spratt cautions that it is primarily “designed and calibrated for the US.
“The estimates are based on very large US registries, and though it’s probably somewhat similar across much of the world, there’s probably certain cancer types that are more region specific ― especially something like stomach cancer or certain types of head and neck cancer in parts of Asia, for example,” he said.
Although the app’s COVID-19 data are specific to the county level in the United States, elsewhere in the world, it is only country specific.
“We’re using the best data we have for coronavirus, but everyone knows we still have large data gaps,” he acknowledged.
How Accurate?
Asked to comment on the app, Richard Bleicher, MD, leader of the Breast Cancer Program at Fox Chase Cancer Center, Philadelphia, praised the effort and the goal but had some concerns.
“Several questions arise, most important of which is, How accurate is this, and how has this been validated, if at all ― especially as it is too soon to see the outcomes of patients affected in this pandemic?” he told Medscape Medical News.
“We are imposing delays on a broad scale because of the coronavirus, and we are getting continuously changing data as we test more patients. But both situations are novel and may not be accurately represented by the data being pulled, because the datasets use patients from a few years ago, and confounders in these datasets may not apply to this situation,” Bleicher continued.
Although acknowledging the “value in delineating the risk of dying from cancer vs the risk of dying from the SARS-CoV-2 pandemic,” Bleicher urged caution in using the tool to make individual patient decisions.
“We need to remember that the best of modeling ... can be wildly inaccurate and needs to be validated using patients having the circumstances in question. ... This won’t be possible until long after the pandemic is completed, and so the model’s accuracy remains unknown.”
That sentiment was echoed by Giampaolo Bianchini, MD, head of the Breast Cancer Group, Department of Medical Oncology, Ospedale San Raffaele, in Milan, Italy.
“Arbitrarily postponing and modifying treatment strategies including surgery, radiation therapy, and medical therapy without properly balancing the risk/benefit ratio may lead to significantly worse cancer-related outcomes, which largely exceed the actual risks for COVID,” he wrote in an email.
“The OncCOVID app is a remarkable attempt to fill the gap between perception and estimation,” he said. The app provides side by side the COVID-19 risk estimation and the consequences of arbitrary deviation from the standard of care, observed Bianchini.
However, he pointed out weaknesses, including the fact that the “data generated in literature are not always of high quality and do not take into consideration relevant characteristics of the disease and treatment benefit. It should for sure be used, but then also interpreted with caution.”
Another Italian group responded more positively.
“In our opinion, it could be a useful tool for clinicians,” wrote colleagues Alessio Cortelinni and Giampiero Porzio, both medical oncologists at San Salvatore Hospital and the University of L’Aquila, in Italy. “This Web app might assist clinicians in balancing the risk/benefit ratio of being treated and/or access to the outpatient cancer center for each kind of patient (both early and advanced stages), in order to make a more tailored counseling,” they wrote in an email. “Importantly, the Web app might help those clinicians who work ‘alone,’ in peripheral centers, without resources, colleagues, and multidisciplinary tumor boards on whom they can rely.”
Bleicher, who was involved in the COVID-19 Breast Cancer Consortium’s recommendations for prioritizing breast cancer treatment, summarized that the app “may end up being close or accurate, but we won’t know except in hindsight.”
This article first appeared on Medscape.com.
Huntington’s disease biomarkers appear 24 years before clinical symptoms
, according to a study published in the June Lancet Neurology. The data come from the Huntington’s disease Young Adult Study (HD-YAS) conducted in the United Kingdom.
The genetic cause of Huntington’s disease provides a potential target for biomarker treatment, wrote joint first authors Rachael I. Scahill, PhD, and Paul Zeun, BMBS, of University College London and colleagues.
“A detailed characterization of the premanifest period in Huntington’s disease is crucial for disease staging, informing the optimum time to initiate treatments, and identifying biomarkers for future trials in people with premanifest Huntington’s disease (preHD),” they said.
Identifying biomarkers of pre-Huntington’s disease
For their study, the researchers recruited 64 young adults with presymptomatic Huntington’s disease (preHD) and 67 controls, with an average age of 29 years. Brain imaging was conducted between Aug. 2, 2017, and April 25, 2019. Individuals with preexisting measurable cognitive and psychiatric disorders were excluded.
The researchers found no significant evidence of cognitive or psychiatric impairment in the preHD group at 23.6 years from the predicted onset of symptoms. The preHD group showed smaller putamen volumes, compared with controls, but this difference had no apparent relation to the timing of symptom onset, the researchers said.
Brain imaging revealed elevations in the CSF mutant huntingtin, neurofilament light protein (NfL), YKL-40, and plasma NfL among individuals with preHD, compared with controls. Of these, CSF NfL showed the highest effect size of measures in the study and showed a significant increasing association with estimated years to the onset of clinical symptoms of HD carriers. Overall, 53% of individuals with preHD had CSF NfL values in the normal range, and 47% had elevated values, compared with controls.
“NfL is therefore a potential candidate to provide a measure of disease progression in early preHD and might eventually be used as a marker of response to treatment in future preventive trials,” the researchers said.
The study findings were limited by several factors including potential underpowering to detect associations with age and CAG gene segment repeats, the researchers noted.
However, “By identifying a cohort of individuals with preHD and no detectable functional impairment but who begin to exhibit subtle elevations in select biological measures of neurodegeneration, we have highlighted a crucial point early in the disease process,” they concluded.
“Intervening at this stage might offer the prospect of delaying or preventing further neurodegeneration while function is intact, giving gene carriers many more years of life without impairment,” they added.
What is the best window for treatment?
The study is “particularly important since the absence of any subclinical symptoms in preHD individuals far from onset shows that the abnormal developmental aspect of Huntington’s disease has no substantial effect on adults’ clinical pattern,” wrote Anne-Catherine Bachoud-Lévi, MD, of Université Paris Est, Créteil, France, in an accompanying comment.
“The most robust findings of [the study] are the sensitiveness of NfL, compared with mutant huntingtin in CSF of individuals with preHD, and that degenerative rather than developmental disorders are clinically relevant,” she said. However, potential limitations to the study include the exclusion absence of language and calculation as part of the cognitive assessments, she noted. “Ideally, more sensitive cognitive tasks including these domains should be designed for preHD participants.”
In addition, the risks versus benefits of any long-term treatment must be considered, Dr. Bachoud-Lévi noted.
“The best window for treatment should instead target the time when a detectable subclinical slope of cognitive performance allows for predicting disease onset within a few years,” she said. “Turning to machine learning methodology, such as that in oncology, might also permit combining the best window and the best disease-modifying therapy for individuals with preHD,” she added.
The study was supported by the Wellcome Trust, CHDI Foundation. The researchers had no financial conflicts to disclose. Dr. Bachoud-Lévi disclosed grants and personal fees from Roche, and grants from the French Ministry of Health and Direction de la Recherche Clinique.
SOURCES: Scahill RI et al. Lancet Neurol. 2020 June;19:502-12; Bachoud-Lévi A-C. Lancet Neurol. 2020 June;19:473-5.
, according to a study published in the June Lancet Neurology. The data come from the Huntington’s disease Young Adult Study (HD-YAS) conducted in the United Kingdom.
The genetic cause of Huntington’s disease provides a potential target for biomarker treatment, wrote joint first authors Rachael I. Scahill, PhD, and Paul Zeun, BMBS, of University College London and colleagues.
“A detailed characterization of the premanifest period in Huntington’s disease is crucial for disease staging, informing the optimum time to initiate treatments, and identifying biomarkers for future trials in people with premanifest Huntington’s disease (preHD),” they said.
Identifying biomarkers of pre-Huntington’s disease
For their study, the researchers recruited 64 young adults with presymptomatic Huntington’s disease (preHD) and 67 controls, with an average age of 29 years. Brain imaging was conducted between Aug. 2, 2017, and April 25, 2019. Individuals with preexisting measurable cognitive and psychiatric disorders were excluded.
The researchers found no significant evidence of cognitive or psychiatric impairment in the preHD group at 23.6 years from the predicted onset of symptoms. The preHD group showed smaller putamen volumes, compared with controls, but this difference had no apparent relation to the timing of symptom onset, the researchers said.
Brain imaging revealed elevations in the CSF mutant huntingtin, neurofilament light protein (NfL), YKL-40, and plasma NfL among individuals with preHD, compared with controls. Of these, CSF NfL showed the highest effect size of measures in the study and showed a significant increasing association with estimated years to the onset of clinical symptoms of HD carriers. Overall, 53% of individuals with preHD had CSF NfL values in the normal range, and 47% had elevated values, compared with controls.
“NfL is therefore a potential candidate to provide a measure of disease progression in early preHD and might eventually be used as a marker of response to treatment in future preventive trials,” the researchers said.
The study findings were limited by several factors including potential underpowering to detect associations with age and CAG gene segment repeats, the researchers noted.
However, “By identifying a cohort of individuals with preHD and no detectable functional impairment but who begin to exhibit subtle elevations in select biological measures of neurodegeneration, we have highlighted a crucial point early in the disease process,” they concluded.
“Intervening at this stage might offer the prospect of delaying or preventing further neurodegeneration while function is intact, giving gene carriers many more years of life without impairment,” they added.
What is the best window for treatment?
The study is “particularly important since the absence of any subclinical symptoms in preHD individuals far from onset shows that the abnormal developmental aspect of Huntington’s disease has no substantial effect on adults’ clinical pattern,” wrote Anne-Catherine Bachoud-Lévi, MD, of Université Paris Est, Créteil, France, in an accompanying comment.
“The most robust findings of [the study] are the sensitiveness of NfL, compared with mutant huntingtin in CSF of individuals with preHD, and that degenerative rather than developmental disorders are clinically relevant,” she said. However, potential limitations to the study include the exclusion absence of language and calculation as part of the cognitive assessments, she noted. “Ideally, more sensitive cognitive tasks including these domains should be designed for preHD participants.”
In addition, the risks versus benefits of any long-term treatment must be considered, Dr. Bachoud-Lévi noted.
“The best window for treatment should instead target the time when a detectable subclinical slope of cognitive performance allows for predicting disease onset within a few years,” she said. “Turning to machine learning methodology, such as that in oncology, might also permit combining the best window and the best disease-modifying therapy for individuals with preHD,” she added.
The study was supported by the Wellcome Trust, CHDI Foundation. The researchers had no financial conflicts to disclose. Dr. Bachoud-Lévi disclosed grants and personal fees from Roche, and grants from the French Ministry of Health and Direction de la Recherche Clinique.
SOURCES: Scahill RI et al. Lancet Neurol. 2020 June;19:502-12; Bachoud-Lévi A-C. Lancet Neurol. 2020 June;19:473-5.
, according to a study published in the June Lancet Neurology. The data come from the Huntington’s disease Young Adult Study (HD-YAS) conducted in the United Kingdom.
The genetic cause of Huntington’s disease provides a potential target for biomarker treatment, wrote joint first authors Rachael I. Scahill, PhD, and Paul Zeun, BMBS, of University College London and colleagues.
“A detailed characterization of the premanifest period in Huntington’s disease is crucial for disease staging, informing the optimum time to initiate treatments, and identifying biomarkers for future trials in people with premanifest Huntington’s disease (preHD),” they said.
Identifying biomarkers of pre-Huntington’s disease
For their study, the researchers recruited 64 young adults with presymptomatic Huntington’s disease (preHD) and 67 controls, with an average age of 29 years. Brain imaging was conducted between Aug. 2, 2017, and April 25, 2019. Individuals with preexisting measurable cognitive and psychiatric disorders were excluded.
The researchers found no significant evidence of cognitive or psychiatric impairment in the preHD group at 23.6 years from the predicted onset of symptoms. The preHD group showed smaller putamen volumes, compared with controls, but this difference had no apparent relation to the timing of symptom onset, the researchers said.
Brain imaging revealed elevations in the CSF mutant huntingtin, neurofilament light protein (NfL), YKL-40, and plasma NfL among individuals with preHD, compared with controls. Of these, CSF NfL showed the highest effect size of measures in the study and showed a significant increasing association with estimated years to the onset of clinical symptoms of HD carriers. Overall, 53% of individuals with preHD had CSF NfL values in the normal range, and 47% had elevated values, compared with controls.
“NfL is therefore a potential candidate to provide a measure of disease progression in early preHD and might eventually be used as a marker of response to treatment in future preventive trials,” the researchers said.
The study findings were limited by several factors including potential underpowering to detect associations with age and CAG gene segment repeats, the researchers noted.
However, “By identifying a cohort of individuals with preHD and no detectable functional impairment but who begin to exhibit subtle elevations in select biological measures of neurodegeneration, we have highlighted a crucial point early in the disease process,” they concluded.
“Intervening at this stage might offer the prospect of delaying or preventing further neurodegeneration while function is intact, giving gene carriers many more years of life without impairment,” they added.
What is the best window for treatment?
The study is “particularly important since the absence of any subclinical symptoms in preHD individuals far from onset shows that the abnormal developmental aspect of Huntington’s disease has no substantial effect on adults’ clinical pattern,” wrote Anne-Catherine Bachoud-Lévi, MD, of Université Paris Est, Créteil, France, in an accompanying comment.
“The most robust findings of [the study] are the sensitiveness of NfL, compared with mutant huntingtin in CSF of individuals with preHD, and that degenerative rather than developmental disorders are clinically relevant,” she said. However, potential limitations to the study include the exclusion absence of language and calculation as part of the cognitive assessments, she noted. “Ideally, more sensitive cognitive tasks including these domains should be designed for preHD participants.”
In addition, the risks versus benefits of any long-term treatment must be considered, Dr. Bachoud-Lévi noted.
“The best window for treatment should instead target the time when a detectable subclinical slope of cognitive performance allows for predicting disease onset within a few years,” she said. “Turning to machine learning methodology, such as that in oncology, might also permit combining the best window and the best disease-modifying therapy for individuals with preHD,” she added.
The study was supported by the Wellcome Trust, CHDI Foundation. The researchers had no financial conflicts to disclose. Dr. Bachoud-Lévi disclosed grants and personal fees from Roche, and grants from the French Ministry of Health and Direction de la Recherche Clinique.
SOURCES: Scahill RI et al. Lancet Neurol. 2020 June;19:502-12; Bachoud-Lévi A-C. Lancet Neurol. 2020 June;19:473-5.
FROM LANCET NEUROLOGY
‘A good and peaceful death’: Cancer hospice during the pandemic
Lillie Shockney, RN, MAS, a two-time breast cancer survivor and adjunct professor at Johns Hopkins School of Nursing in Baltimore, Maryland, mourns the many losses that her patients with advanced cancer now face in the midst of the COVID-19 pandemic. But in the void of the usual support networks and treatment plans, she sees the resurgence of something that has recently been crowded out: hospice.
The pandemic has forced patients and their physicians to reassess the risk/benefit balance of continuing or embarking on yet another cancer treatment.
“It’s one of the pearls that we will get out of this nightmare,” said Ms. Shockney, who recently retired as administrative director of the cancer survivorship programs at the Sidney Kimmel Comprehensive Cancer Center.
“Physicians have been taught to treat the disease – so as long as there’s a treatment they give another treatment,” she told Medscape Medical News during a Zoom call from her home. “But for some patients with advanced disease, those treatments were making them very sick, so they were trading longevity over quality of life.”
Of course, longevity has never been a guarantee with cancer treatment, and even less so now, with the risk of COVID-19.
“This is going to bring them to some hard discussions,” says Brenda Nevidjon, RN, MSN, chief executive officer at the Oncology Nursing Society.
“We’ve known for a long time that there are patients who are on third- and fourth-round treatment options that have very little evidence of prolonging life or quality of life,” she told Medscape Medical News. “Do we bring these people out of their home to a setting where there could be a fair number of COVID-positive patients? Do we expose them to that?”
Across the world, these dilemmas are pushing cancer specialists to initiate discussions of hospice sooner with patients who have advanced disease, and with more clarity than before.
One of the reasons such conversations have often been avoided is that the concept of hospice is generally misunderstood, said Ms. Shockney.
“Patients think ‘you’re giving up on me, you’ve abandoned me’, but hospice is all about preserving the remainder of their quality of life and letting them have time with family and time to fulfill those elements of experiencing a good and peaceful death,” she said.
Indeed, hospice is “a benefit meant for somebody with at least a 6-month horizon,” agrees Ms. Nevidjon. Yet the average length of hospice in the United States is just 5 days. “It’s at the very, very end, and yet for some of these patients the 6 months they could get in hospice might be a better quality of life than the 4 months on another whole plan of chemotherapy. I can’t imagine that on the backside of this pandemic we will not have learned and we won’t start to change practices around initiating more of these conversations.”
Silver lining of this pandemic?
It’s too early into the pandemic to have hard data on whether hospice uptake has increased, but “it’s encouraging to hear that hospice is being discussed and offered sooner as an alternative to that third- or fourth-round chemo,” said Lori Bishop, MHA, RN, vice president of palliative and advanced care at the National Hospice and Palliative Care Organization.
“I agree that improving informed-decision discussions and timely access to hospice is a silver lining of the pandemic,” she told Medscape Medical News.
But she points out that today’s hospice looks quite different than it did before the pandemic, with the immediate and very obvious difference being telehealth, which was not widely utilized previously.
In March, the Centers for Medicare & Medicaid Services expanded telehealth options for hospice providers, something that Ms. Bishop and other hospice providers hope will remain in place after the pandemic passes.
“Telehealth visits are offered to replace some in-home visits both to minimize risk of exposure to COVID-19 and reduce the drain on personal protective equipment,” Bishop explained.
“In-patient hospice programs are also finding unique ways to provide support and connect patients to their loved ones: visitors are allowed but limited to one or two. Music and pet therapy are being provided through the window or virtually and devices such as iPads are being used to help patients connect with loved ones,” she said.
Telehealth links patients out of loneliness, but the one thing it cannot do is provide the comfort of touch – an important part of any hospice program.
“Hand-holding ... I miss that a lot,” says Ms. Shockney, her eyes filling with tears. “When you take somebody’s hand, you don’t even have to speak; that connection, and eye contact, is all you need to help that person emotionally heal.”
This article first appeared on Medscape.com.
Lillie Shockney, RN, MAS, a two-time breast cancer survivor and adjunct professor at Johns Hopkins School of Nursing in Baltimore, Maryland, mourns the many losses that her patients with advanced cancer now face in the midst of the COVID-19 pandemic. But in the void of the usual support networks and treatment plans, she sees the resurgence of something that has recently been crowded out: hospice.
The pandemic has forced patients and their physicians to reassess the risk/benefit balance of continuing or embarking on yet another cancer treatment.
“It’s one of the pearls that we will get out of this nightmare,” said Ms. Shockney, who recently retired as administrative director of the cancer survivorship programs at the Sidney Kimmel Comprehensive Cancer Center.
“Physicians have been taught to treat the disease – so as long as there’s a treatment they give another treatment,” she told Medscape Medical News during a Zoom call from her home. “But for some patients with advanced disease, those treatments were making them very sick, so they were trading longevity over quality of life.”
Of course, longevity has never been a guarantee with cancer treatment, and even less so now, with the risk of COVID-19.
“This is going to bring them to some hard discussions,” says Brenda Nevidjon, RN, MSN, chief executive officer at the Oncology Nursing Society.
“We’ve known for a long time that there are patients who are on third- and fourth-round treatment options that have very little evidence of prolonging life or quality of life,” she told Medscape Medical News. “Do we bring these people out of their home to a setting where there could be a fair number of COVID-positive patients? Do we expose them to that?”
Across the world, these dilemmas are pushing cancer specialists to initiate discussions of hospice sooner with patients who have advanced disease, and with more clarity than before.
One of the reasons such conversations have often been avoided is that the concept of hospice is generally misunderstood, said Ms. Shockney.
“Patients think ‘you’re giving up on me, you’ve abandoned me’, but hospice is all about preserving the remainder of their quality of life and letting them have time with family and time to fulfill those elements of experiencing a good and peaceful death,” she said.
Indeed, hospice is “a benefit meant for somebody with at least a 6-month horizon,” agrees Ms. Nevidjon. Yet the average length of hospice in the United States is just 5 days. “It’s at the very, very end, and yet for some of these patients the 6 months they could get in hospice might be a better quality of life than the 4 months on another whole plan of chemotherapy. I can’t imagine that on the backside of this pandemic we will not have learned and we won’t start to change practices around initiating more of these conversations.”
Silver lining of this pandemic?
It’s too early into the pandemic to have hard data on whether hospice uptake has increased, but “it’s encouraging to hear that hospice is being discussed and offered sooner as an alternative to that third- or fourth-round chemo,” said Lori Bishop, MHA, RN, vice president of palliative and advanced care at the National Hospice and Palliative Care Organization.
“I agree that improving informed-decision discussions and timely access to hospice is a silver lining of the pandemic,” she told Medscape Medical News.
But she points out that today’s hospice looks quite different than it did before the pandemic, with the immediate and very obvious difference being telehealth, which was not widely utilized previously.
In March, the Centers for Medicare & Medicaid Services expanded telehealth options for hospice providers, something that Ms. Bishop and other hospice providers hope will remain in place after the pandemic passes.
“Telehealth visits are offered to replace some in-home visits both to minimize risk of exposure to COVID-19 and reduce the drain on personal protective equipment,” Bishop explained.
“In-patient hospice programs are also finding unique ways to provide support and connect patients to their loved ones: visitors are allowed but limited to one or two. Music and pet therapy are being provided through the window or virtually and devices such as iPads are being used to help patients connect with loved ones,” she said.
Telehealth links patients out of loneliness, but the one thing it cannot do is provide the comfort of touch – an important part of any hospice program.
“Hand-holding ... I miss that a lot,” says Ms. Shockney, her eyes filling with tears. “When you take somebody’s hand, you don’t even have to speak; that connection, and eye contact, is all you need to help that person emotionally heal.”
This article first appeared on Medscape.com.
Lillie Shockney, RN, MAS, a two-time breast cancer survivor and adjunct professor at Johns Hopkins School of Nursing in Baltimore, Maryland, mourns the many losses that her patients with advanced cancer now face in the midst of the COVID-19 pandemic. But in the void of the usual support networks and treatment plans, she sees the resurgence of something that has recently been crowded out: hospice.
The pandemic has forced patients and their physicians to reassess the risk/benefit balance of continuing or embarking on yet another cancer treatment.
“It’s one of the pearls that we will get out of this nightmare,” said Ms. Shockney, who recently retired as administrative director of the cancer survivorship programs at the Sidney Kimmel Comprehensive Cancer Center.
“Physicians have been taught to treat the disease – so as long as there’s a treatment they give another treatment,” she told Medscape Medical News during a Zoom call from her home. “But for some patients with advanced disease, those treatments were making them very sick, so they were trading longevity over quality of life.”
Of course, longevity has never been a guarantee with cancer treatment, and even less so now, with the risk of COVID-19.
“This is going to bring them to some hard discussions,” says Brenda Nevidjon, RN, MSN, chief executive officer at the Oncology Nursing Society.
“We’ve known for a long time that there are patients who are on third- and fourth-round treatment options that have very little evidence of prolonging life or quality of life,” she told Medscape Medical News. “Do we bring these people out of their home to a setting where there could be a fair number of COVID-positive patients? Do we expose them to that?”
Across the world, these dilemmas are pushing cancer specialists to initiate discussions of hospice sooner with patients who have advanced disease, and with more clarity than before.
One of the reasons such conversations have often been avoided is that the concept of hospice is generally misunderstood, said Ms. Shockney.
“Patients think ‘you’re giving up on me, you’ve abandoned me’, but hospice is all about preserving the remainder of their quality of life and letting them have time with family and time to fulfill those elements of experiencing a good and peaceful death,” she said.
Indeed, hospice is “a benefit meant for somebody with at least a 6-month horizon,” agrees Ms. Nevidjon. Yet the average length of hospice in the United States is just 5 days. “It’s at the very, very end, and yet for some of these patients the 6 months they could get in hospice might be a better quality of life than the 4 months on another whole plan of chemotherapy. I can’t imagine that on the backside of this pandemic we will not have learned and we won’t start to change practices around initiating more of these conversations.”
Silver lining of this pandemic?
It’s too early into the pandemic to have hard data on whether hospice uptake has increased, but “it’s encouraging to hear that hospice is being discussed and offered sooner as an alternative to that third- or fourth-round chemo,” said Lori Bishop, MHA, RN, vice president of palliative and advanced care at the National Hospice and Palliative Care Organization.
“I agree that improving informed-decision discussions and timely access to hospice is a silver lining of the pandemic,” she told Medscape Medical News.
But she points out that today’s hospice looks quite different than it did before the pandemic, with the immediate and very obvious difference being telehealth, which was not widely utilized previously.
In March, the Centers for Medicare & Medicaid Services expanded telehealth options for hospice providers, something that Ms. Bishop and other hospice providers hope will remain in place after the pandemic passes.
“Telehealth visits are offered to replace some in-home visits both to minimize risk of exposure to COVID-19 and reduce the drain on personal protective equipment,” Bishop explained.
“In-patient hospice programs are also finding unique ways to provide support and connect patients to their loved ones: visitors are allowed but limited to one or two. Music and pet therapy are being provided through the window or virtually and devices such as iPads are being used to help patients connect with loved ones,” she said.
Telehealth links patients out of loneliness, but the one thing it cannot do is provide the comfort of touch – an important part of any hospice program.
“Hand-holding ... I miss that a lot,” says Ms. Shockney, her eyes filling with tears. “When you take somebody’s hand, you don’t even have to speak; that connection, and eye contact, is all you need to help that person emotionally heal.”
This article first appeared on Medscape.com.
Germline testing in advanced cancer can lead to targeted treatment
The study involved 11,974 patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, using the next-generation sequencing panel MSK-IMPACT.
This testing showed that 17.1% of patients had variants in cancer predisposition genes, and 7.1%-8.6% had variants that could potentially be targeted.
“Of course, these numbers are not static,” commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. “And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.
“Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer,” she added.
Dr. Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology 2020.
Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9%-11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.
“The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment,” said Erin Wysong Hofstatter, MD, from Yale University, New Haven, Conn., in a Highlights of the Day session.
An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. “And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing.”
Implications in cancer treatment
For their study, Dr. Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.
“Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed,” she said. “Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service.”
A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients (n = 849) harbored a targetable pathogenic germline alteration.
BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.
The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Dr. Hofstatter noted that, using strict criteria, 7.1% of patients (n = 849) were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6% (n = 1,003).
Therapeutic action
For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.
Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a poly (ADP-ribose) polymerase (PARP) inhibitor.
Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.
For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.
Looking ahead
The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. “There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated,” she said. “But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1.”
Some questions remain unanswered, she noted, such as: “What percentage of patients undergoing tumor-normal testing signed a germline protocol?” and “Does the population introduce a bias – such as younger patients, family history, and so on?”
It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. “What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?
“But to be fair, it is not easy to seek the germline mutations,” Dr. Meric-Bernstam continued. “These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results.”
An infrastructure is needed to return/counsel/offer cascade testing, and “analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion,” she added.
The study was supported by MSKCC internal funding. Dr. Stadler reported relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Meric-Bernstram reported relationships with numerous pharmaceutical companies.
This article first appeared on Medscape.com.
The study involved 11,974 patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, using the next-generation sequencing panel MSK-IMPACT.
This testing showed that 17.1% of patients had variants in cancer predisposition genes, and 7.1%-8.6% had variants that could potentially be targeted.
“Of course, these numbers are not static,” commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. “And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.
“Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer,” she added.
Dr. Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology 2020.
Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9%-11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.
“The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment,” said Erin Wysong Hofstatter, MD, from Yale University, New Haven, Conn., in a Highlights of the Day session.
An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. “And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing.”
Implications in cancer treatment
For their study, Dr. Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.
“Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed,” she said. “Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service.”
A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients (n = 849) harbored a targetable pathogenic germline alteration.
BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.
The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Dr. Hofstatter noted that, using strict criteria, 7.1% of patients (n = 849) were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6% (n = 1,003).
Therapeutic action
For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.
Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a poly (ADP-ribose) polymerase (PARP) inhibitor.
Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.
For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.
Looking ahead
The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. “There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated,” she said. “But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1.”
Some questions remain unanswered, she noted, such as: “What percentage of patients undergoing tumor-normal testing signed a germline protocol?” and “Does the population introduce a bias – such as younger patients, family history, and so on?”
It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. “What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?
“But to be fair, it is not easy to seek the germline mutations,” Dr. Meric-Bernstam continued. “These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results.”
An infrastructure is needed to return/counsel/offer cascade testing, and “analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion,” she added.
The study was supported by MSKCC internal funding. Dr. Stadler reported relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Meric-Bernstram reported relationships with numerous pharmaceutical companies.
This article first appeared on Medscape.com.
The study involved 11,974 patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, using the next-generation sequencing panel MSK-IMPACT.
This testing showed that 17.1% of patients had variants in cancer predisposition genes, and 7.1%-8.6% had variants that could potentially be targeted.
“Of course, these numbers are not static,” commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. “And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.
“Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer,” she added.
Dr. Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology 2020.
Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9%-11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.
“The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment,” said Erin Wysong Hofstatter, MD, from Yale University, New Haven, Conn., in a Highlights of the Day session.
An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. “And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing.”
Implications in cancer treatment
For their study, Dr. Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.
“Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed,” she said. “Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service.”
A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients (n = 849) harbored a targetable pathogenic germline alteration.
BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.
The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Dr. Hofstatter noted that, using strict criteria, 7.1% of patients (n = 849) were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6% (n = 1,003).
Therapeutic action
For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.
Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a poly (ADP-ribose) polymerase (PARP) inhibitor.
Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.
For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.
Looking ahead
The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. “There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated,” she said. “But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1.”
Some questions remain unanswered, she noted, such as: “What percentage of patients undergoing tumor-normal testing signed a germline protocol?” and “Does the population introduce a bias – such as younger patients, family history, and so on?”
It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. “What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?
“But to be fair, it is not easy to seek the germline mutations,” Dr. Meric-Bernstam continued. “These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results.”
An infrastructure is needed to return/counsel/offer cascade testing, and “analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion,” she added.
The study was supported by MSKCC internal funding. Dr. Stadler reported relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Meric-Bernstram reported relationships with numerous pharmaceutical companies.
This article first appeared on Medscape.com.
FROM ASCO 2020
New research confirms the efficacy and safety of onasemnogene abeparvovec for SMA
The research was presented online as part of the 2020 AAN Science Highlights.
SMA results from a mutation in SMN1, which encodes the SMN protein necessary for motor function. Deficiency of this protein causes motor neurons to die, resulting in severe muscle weakness. At 2 years of age, untreated patients with SMA type 1 generally die or require permanent ventilation.
The Food and Drug Administration approved onasemnogene abeparvovec-xioi under the brand name Zolgensma in May 2019. The gene-replacement therapy, which is administered once intravenously, delivers a fully functional copy of human SMN1 into the target motor neuron cells. It is indicated as treatment for SMA in infants younger than 2 years of age.
Preliminary STR1VE data
Preliminary data from the phase 3 STR1VE study were scheduled to be presented at the meeting. The open-label, single-arm, single-dose study enrolled symptomatic patients with SMA type 1 (SMA1) at multiple US sites. Enrollment was completed in May 2019.
The study included 10 male patients and 12 female patients. Participants’ mean age at dosing was 3.7 months. Of 19 patients who could have reached age 13.6 months at data cutoff, 17 (89.5%) were surviving without permanent ventilation, compared with a 25% survival rate among untreated patients. One of the 19 patients died, and the event was judged to be unrelated to treatment. Another of the 19 reached a respiratory endpoint or withdrew consent.
The population’s mean baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score was 32. This score increased by 6.9, 11.7, and 14.3 points at months 1, 3, and 5, respectively. Half of the 22 infants sat independently for 30 or more seconds, and this milestone was achieved at a mean of 8.2 months after treatment. Five of six (83%) patients age 18 months or older sat independently for 30 or more seconds, which was one of the study’s primary endpoints. As of March 8, 2019, treatment-emergent adverse events of special interest were transient and not associated with any sequelae.
The STR1VE study was sponsored by AveXis, the maker of onasemnogene abeparvovec-xioi. Several of the investigators are employees of AveXis, and others received funding from the company.
Long-term follow-up in START
Long-term follow-up data for participants in the phase 1/2a START study also were scheduled to be presented. Patients who completed START were eligible to participate, and the trial’s primary aim was to evaluate the long-term safety of onasemnogene abeparvovec-xioi. Patients are intended to have five annual visits, followed by 10 annual phone calls, and the investigators request local physicians or neurologists to transfer patient records. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include evaluation of the maintenance of developmental milestones.
As of May 31, 2019, 13 patients in two cohorts had been enrolled and had had a baseline visit. For patients in Cohort 2, the mean age and time since dosing were 4.2 years and 3.9 years, respectively. All patients in Cohort 2 were alive and did not require permanent ventilation. Participants did not lose any developmental milestones that they had achieved at the end of START. Two patients were able to walk, and two could stand with assistance during long-term follow-up. This result suggests the durability of the treatment’s effect. No new treatment-related serious adverse events or adverse events of special interest had occurred as of March 8, 2019.
“We know from accumulating experience that treating infants by gene therapy is safe,” said Jerry R. Mendell, MD, the principal investigator and an attending neurologist at Nationwide Children’s Hospital in Columbus, Ohio. “Of the 15 patients we had in our first trial, only four adverse events related to the gene delivery were encountered, and only two of these were considered serious adverse events [i.e., liver enzymes that were 10 times greater than normal laboratory levels]. These laboratory tests occurred without accompanying clinical symptoms or signs. All were suppressed by corticosteroids and related to the liver inflammation. This pattern of safety has been seen in our very large gene therapy experience. No long-term surprises were encountered.”
The START study was sponsored by AveXis. Several of the investigators are employees of AveXis, and others received funding from the company.
Update on the SPR1NT study
Interim safety and efficacy data from the ongoing SPR1NT study, which includes presymptomatic patients, also were scheduled to be presented. The trial “was built on the basic premise that spinal motor neuron degeneration associated with SMN protein deficiency begins in utero, continues to progress rapidly during the first months of life, and is irreversible,” said Kevin Strauss, MD, medical director of the Clinic for Special Children in Strasburg, Pennsylvania. “SPR1NT leveraged the advantages conferred by carrier testing and newborn screening programs for SMA, which allowed the first 22 children enrolled to have a confirmed molecular diagnosis between 1 and 26 days of postnatal life, before the onset of dysphagia, respiratory compromise, or overt weakness.”
In this multicenter, open-label, phase 3 trial, presymptomatic patients age 6 weeks or younger who are expected to develop SMA receive onasemnogene abeparvovec-xioi once and are evaluated during 18 or 24 months. The primary outcomes are sitting for 30 or more seconds for infants with two copies of SMN2 and standing unassisted for infants with three copies of SMN2.
As of December 31, 2019, 29 infants had been treated in the efficacy group at a mean age of 20.6 days among infants with two copies of SMN2 and 28.7 days among infants with three copies of SMN2. All patients are alive, and no patient in SPR1NT required ventilation support at last visit. Among 14 patients with two copies of SMN2, all achieved CHOP INTEND scores of 50 or greater, which exceeds the maximal score observed in untreated patients. Eight have achieved sitting, seven of whom achieved it within the World Health Organization sitting age range of 3.8-9.2 months. The other six patients have not yet passed the WHO developmental window. Among 15 patients with three copies of SMN2, four stood independently and three walked independently, all within the WHO developmental windows of 6.9-16.9 months and 8.2-17.6 months, respectively. The other patients have not yet passed the WHO developmental window. No patient in either cohort required a feeding tube, and most remained within the normal weight range. Treatment-emergent adverse events of special interest were reported in 16 patients. The study is ongoing, and patients continue to meet primary endpoints.
“Comparing functional and motor indices between these two groups [i.e., patients with two copies of SMN2 and those with three copies] should contribute to our understanding of how motor neuron loss during fetal development may impact long-term neurological outcomes over the arc of life and could even form a basis for considering antenatal gene therapy for severe forms of SMA,” said Dr. Strauss.
SPR1NT was funded by AveXis. Several of the investigators are employees of AveXis, and others received funding from the company.
Combination therapy may be a possibility
A benefit of onasemnogene abeparvovec-xioi is that the adeno-associated virus that delivers it does not integrate itself into the genome, said Darryl C. De Vivo, MD, Sidney Carter professor of neurology and professor of pediatrics at Columbia University in New York. “The bad news is that every time the cell divides, the gene therapy goes to one of the two daughter cells, but not to both. ... That means the effectiveness, in theory, would be reduced by 50% with each cell division, possibly affecting the durability of treatment.” The fact that brain and spinal cord neurons are presumed to be fully populated around the time of birth partly mitigates this concern, he added. “There isn’t too much additional cell division going on in neurons after birth at a time when the gene therapy would be administered.”
Furthermore, the cellular distribution of the gene therapy within the nervous system, which is unclear, might affect the therapy’s effect. “These are largely unanswered questions,” said Dr. De Vivo. “The answers to these questions only will come with continued observation of patients who have been treated.”
Considering that nusinersen, the antisense oligonucleotide also approved for SMA, targets SMN2, and the gene therapy replaces SMN1, “there may be some wisdom in thinking about combination therapy,” said Dr. De Vivo. “There’s no doubt that these therapeutic agents are effective,” and continued follow-up will clarify their comparative efficacy, he concluded.
SOURCES: Day JW, et al. AAN 2020. Abstract S27.001. Mendell JR, et al. AAN 2020. Abstract S27.002. Strauss KA, et al. AAN 2020. Abstract S27.003.
The research was presented online as part of the 2020 AAN Science Highlights.
SMA results from a mutation in SMN1, which encodes the SMN protein necessary for motor function. Deficiency of this protein causes motor neurons to die, resulting in severe muscle weakness. At 2 years of age, untreated patients with SMA type 1 generally die or require permanent ventilation.
The Food and Drug Administration approved onasemnogene abeparvovec-xioi under the brand name Zolgensma in May 2019. The gene-replacement therapy, which is administered once intravenously, delivers a fully functional copy of human SMN1 into the target motor neuron cells. It is indicated as treatment for SMA in infants younger than 2 years of age.
Preliminary STR1VE data
Preliminary data from the phase 3 STR1VE study were scheduled to be presented at the meeting. The open-label, single-arm, single-dose study enrolled symptomatic patients with SMA type 1 (SMA1) at multiple US sites. Enrollment was completed in May 2019.
The study included 10 male patients and 12 female patients. Participants’ mean age at dosing was 3.7 months. Of 19 patients who could have reached age 13.6 months at data cutoff, 17 (89.5%) were surviving without permanent ventilation, compared with a 25% survival rate among untreated patients. One of the 19 patients died, and the event was judged to be unrelated to treatment. Another of the 19 reached a respiratory endpoint or withdrew consent.
The population’s mean baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score was 32. This score increased by 6.9, 11.7, and 14.3 points at months 1, 3, and 5, respectively. Half of the 22 infants sat independently for 30 or more seconds, and this milestone was achieved at a mean of 8.2 months after treatment. Five of six (83%) patients age 18 months or older sat independently for 30 or more seconds, which was one of the study’s primary endpoints. As of March 8, 2019, treatment-emergent adverse events of special interest were transient and not associated with any sequelae.
The STR1VE study was sponsored by AveXis, the maker of onasemnogene abeparvovec-xioi. Several of the investigators are employees of AveXis, and others received funding from the company.
Long-term follow-up in START
Long-term follow-up data for participants in the phase 1/2a START study also were scheduled to be presented. Patients who completed START were eligible to participate, and the trial’s primary aim was to evaluate the long-term safety of onasemnogene abeparvovec-xioi. Patients are intended to have five annual visits, followed by 10 annual phone calls, and the investigators request local physicians or neurologists to transfer patient records. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include evaluation of the maintenance of developmental milestones.
As of May 31, 2019, 13 patients in two cohorts had been enrolled and had had a baseline visit. For patients in Cohort 2, the mean age and time since dosing were 4.2 years and 3.9 years, respectively. All patients in Cohort 2 were alive and did not require permanent ventilation. Participants did not lose any developmental milestones that they had achieved at the end of START. Two patients were able to walk, and two could stand with assistance during long-term follow-up. This result suggests the durability of the treatment’s effect. No new treatment-related serious adverse events or adverse events of special interest had occurred as of March 8, 2019.
“We know from accumulating experience that treating infants by gene therapy is safe,” said Jerry R. Mendell, MD, the principal investigator and an attending neurologist at Nationwide Children’s Hospital in Columbus, Ohio. “Of the 15 patients we had in our first trial, only four adverse events related to the gene delivery were encountered, and only two of these were considered serious adverse events [i.e., liver enzymes that were 10 times greater than normal laboratory levels]. These laboratory tests occurred without accompanying clinical symptoms or signs. All were suppressed by corticosteroids and related to the liver inflammation. This pattern of safety has been seen in our very large gene therapy experience. No long-term surprises were encountered.”
The START study was sponsored by AveXis. Several of the investigators are employees of AveXis, and others received funding from the company.
Update on the SPR1NT study
Interim safety and efficacy data from the ongoing SPR1NT study, which includes presymptomatic patients, also were scheduled to be presented. The trial “was built on the basic premise that spinal motor neuron degeneration associated with SMN protein deficiency begins in utero, continues to progress rapidly during the first months of life, and is irreversible,” said Kevin Strauss, MD, medical director of the Clinic for Special Children in Strasburg, Pennsylvania. “SPR1NT leveraged the advantages conferred by carrier testing and newborn screening programs for SMA, which allowed the first 22 children enrolled to have a confirmed molecular diagnosis between 1 and 26 days of postnatal life, before the onset of dysphagia, respiratory compromise, or overt weakness.”
In this multicenter, open-label, phase 3 trial, presymptomatic patients age 6 weeks or younger who are expected to develop SMA receive onasemnogene abeparvovec-xioi once and are evaluated during 18 or 24 months. The primary outcomes are sitting for 30 or more seconds for infants with two copies of SMN2 and standing unassisted for infants with three copies of SMN2.
As of December 31, 2019, 29 infants had been treated in the efficacy group at a mean age of 20.6 days among infants with two copies of SMN2 and 28.7 days among infants with three copies of SMN2. All patients are alive, and no patient in SPR1NT required ventilation support at last visit. Among 14 patients with two copies of SMN2, all achieved CHOP INTEND scores of 50 or greater, which exceeds the maximal score observed in untreated patients. Eight have achieved sitting, seven of whom achieved it within the World Health Organization sitting age range of 3.8-9.2 months. The other six patients have not yet passed the WHO developmental window. Among 15 patients with three copies of SMN2, four stood independently and three walked independently, all within the WHO developmental windows of 6.9-16.9 months and 8.2-17.6 months, respectively. The other patients have not yet passed the WHO developmental window. No patient in either cohort required a feeding tube, and most remained within the normal weight range. Treatment-emergent adverse events of special interest were reported in 16 patients. The study is ongoing, and patients continue to meet primary endpoints.
“Comparing functional and motor indices between these two groups [i.e., patients with two copies of SMN2 and those with three copies] should contribute to our understanding of how motor neuron loss during fetal development may impact long-term neurological outcomes over the arc of life and could even form a basis for considering antenatal gene therapy for severe forms of SMA,” said Dr. Strauss.
SPR1NT was funded by AveXis. Several of the investigators are employees of AveXis, and others received funding from the company.
Combination therapy may be a possibility
A benefit of onasemnogene abeparvovec-xioi is that the adeno-associated virus that delivers it does not integrate itself into the genome, said Darryl C. De Vivo, MD, Sidney Carter professor of neurology and professor of pediatrics at Columbia University in New York. “The bad news is that every time the cell divides, the gene therapy goes to one of the two daughter cells, but not to both. ... That means the effectiveness, in theory, would be reduced by 50% with each cell division, possibly affecting the durability of treatment.” The fact that brain and spinal cord neurons are presumed to be fully populated around the time of birth partly mitigates this concern, he added. “There isn’t too much additional cell division going on in neurons after birth at a time when the gene therapy would be administered.”
Furthermore, the cellular distribution of the gene therapy within the nervous system, which is unclear, might affect the therapy’s effect. “These are largely unanswered questions,” said Dr. De Vivo. “The answers to these questions only will come with continued observation of patients who have been treated.”
Considering that nusinersen, the antisense oligonucleotide also approved for SMA, targets SMN2, and the gene therapy replaces SMN1, “there may be some wisdom in thinking about combination therapy,” said Dr. De Vivo. “There’s no doubt that these therapeutic agents are effective,” and continued follow-up will clarify their comparative efficacy, he concluded.
SOURCES: Day JW, et al. AAN 2020. Abstract S27.001. Mendell JR, et al. AAN 2020. Abstract S27.002. Strauss KA, et al. AAN 2020. Abstract S27.003.
The research was presented online as part of the 2020 AAN Science Highlights.
SMA results from a mutation in SMN1, which encodes the SMN protein necessary for motor function. Deficiency of this protein causes motor neurons to die, resulting in severe muscle weakness. At 2 years of age, untreated patients with SMA type 1 generally die or require permanent ventilation.
The Food and Drug Administration approved onasemnogene abeparvovec-xioi under the brand name Zolgensma in May 2019. The gene-replacement therapy, which is administered once intravenously, delivers a fully functional copy of human SMN1 into the target motor neuron cells. It is indicated as treatment for SMA in infants younger than 2 years of age.
Preliminary STR1VE data
Preliminary data from the phase 3 STR1VE study were scheduled to be presented at the meeting. The open-label, single-arm, single-dose study enrolled symptomatic patients with SMA type 1 (SMA1) at multiple US sites. Enrollment was completed in May 2019.
The study included 10 male patients and 12 female patients. Participants’ mean age at dosing was 3.7 months. Of 19 patients who could have reached age 13.6 months at data cutoff, 17 (89.5%) were surviving without permanent ventilation, compared with a 25% survival rate among untreated patients. One of the 19 patients died, and the event was judged to be unrelated to treatment. Another of the 19 reached a respiratory endpoint or withdrew consent.
The population’s mean baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score was 32. This score increased by 6.9, 11.7, and 14.3 points at months 1, 3, and 5, respectively. Half of the 22 infants sat independently for 30 or more seconds, and this milestone was achieved at a mean of 8.2 months after treatment. Five of six (83%) patients age 18 months or older sat independently for 30 or more seconds, which was one of the study’s primary endpoints. As of March 8, 2019, treatment-emergent adverse events of special interest were transient and not associated with any sequelae.
The STR1VE study was sponsored by AveXis, the maker of onasemnogene abeparvovec-xioi. Several of the investigators are employees of AveXis, and others received funding from the company.
Long-term follow-up in START
Long-term follow-up data for participants in the phase 1/2a START study also were scheduled to be presented. Patients who completed START were eligible to participate, and the trial’s primary aim was to evaluate the long-term safety of onasemnogene abeparvovec-xioi. Patients are intended to have five annual visits, followed by 10 annual phone calls, and the investigators request local physicians or neurologists to transfer patient records. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include evaluation of the maintenance of developmental milestones.
As of May 31, 2019, 13 patients in two cohorts had been enrolled and had had a baseline visit. For patients in Cohort 2, the mean age and time since dosing were 4.2 years and 3.9 years, respectively. All patients in Cohort 2 were alive and did not require permanent ventilation. Participants did not lose any developmental milestones that they had achieved at the end of START. Two patients were able to walk, and two could stand with assistance during long-term follow-up. This result suggests the durability of the treatment’s effect. No new treatment-related serious adverse events or adverse events of special interest had occurred as of March 8, 2019.
“We know from accumulating experience that treating infants by gene therapy is safe,” said Jerry R. Mendell, MD, the principal investigator and an attending neurologist at Nationwide Children’s Hospital in Columbus, Ohio. “Of the 15 patients we had in our first trial, only four adverse events related to the gene delivery were encountered, and only two of these were considered serious adverse events [i.e., liver enzymes that were 10 times greater than normal laboratory levels]. These laboratory tests occurred without accompanying clinical symptoms or signs. All were suppressed by corticosteroids and related to the liver inflammation. This pattern of safety has been seen in our very large gene therapy experience. No long-term surprises were encountered.”
The START study was sponsored by AveXis. Several of the investigators are employees of AveXis, and others received funding from the company.
Update on the SPR1NT study
Interim safety and efficacy data from the ongoing SPR1NT study, which includes presymptomatic patients, also were scheduled to be presented. The trial “was built on the basic premise that spinal motor neuron degeneration associated with SMN protein deficiency begins in utero, continues to progress rapidly during the first months of life, and is irreversible,” said Kevin Strauss, MD, medical director of the Clinic for Special Children in Strasburg, Pennsylvania. “SPR1NT leveraged the advantages conferred by carrier testing and newborn screening programs for SMA, which allowed the first 22 children enrolled to have a confirmed molecular diagnosis between 1 and 26 days of postnatal life, before the onset of dysphagia, respiratory compromise, or overt weakness.”
In this multicenter, open-label, phase 3 trial, presymptomatic patients age 6 weeks or younger who are expected to develop SMA receive onasemnogene abeparvovec-xioi once and are evaluated during 18 or 24 months. The primary outcomes are sitting for 30 or more seconds for infants with two copies of SMN2 and standing unassisted for infants with three copies of SMN2.
As of December 31, 2019, 29 infants had been treated in the efficacy group at a mean age of 20.6 days among infants with two copies of SMN2 and 28.7 days among infants with three copies of SMN2. All patients are alive, and no patient in SPR1NT required ventilation support at last visit. Among 14 patients with two copies of SMN2, all achieved CHOP INTEND scores of 50 or greater, which exceeds the maximal score observed in untreated patients. Eight have achieved sitting, seven of whom achieved it within the World Health Organization sitting age range of 3.8-9.2 months. The other six patients have not yet passed the WHO developmental window. Among 15 patients with three copies of SMN2, four stood independently and three walked independently, all within the WHO developmental windows of 6.9-16.9 months and 8.2-17.6 months, respectively. The other patients have not yet passed the WHO developmental window. No patient in either cohort required a feeding tube, and most remained within the normal weight range. Treatment-emergent adverse events of special interest were reported in 16 patients. The study is ongoing, and patients continue to meet primary endpoints.
“Comparing functional and motor indices between these two groups [i.e., patients with two copies of SMN2 and those with three copies] should contribute to our understanding of how motor neuron loss during fetal development may impact long-term neurological outcomes over the arc of life and could even form a basis for considering antenatal gene therapy for severe forms of SMA,” said Dr. Strauss.
SPR1NT was funded by AveXis. Several of the investigators are employees of AveXis, and others received funding from the company.
Combination therapy may be a possibility
A benefit of onasemnogene abeparvovec-xioi is that the adeno-associated virus that delivers it does not integrate itself into the genome, said Darryl C. De Vivo, MD, Sidney Carter professor of neurology and professor of pediatrics at Columbia University in New York. “The bad news is that every time the cell divides, the gene therapy goes to one of the two daughter cells, but not to both. ... That means the effectiveness, in theory, would be reduced by 50% with each cell division, possibly affecting the durability of treatment.” The fact that brain and spinal cord neurons are presumed to be fully populated around the time of birth partly mitigates this concern, he added. “There isn’t too much additional cell division going on in neurons after birth at a time when the gene therapy would be administered.”
Furthermore, the cellular distribution of the gene therapy within the nervous system, which is unclear, might affect the therapy’s effect. “These are largely unanswered questions,” said Dr. De Vivo. “The answers to these questions only will come with continued observation of patients who have been treated.”
Considering that nusinersen, the antisense oligonucleotide also approved for SMA, targets SMN2, and the gene therapy replaces SMN1, “there may be some wisdom in thinking about combination therapy,” said Dr. De Vivo. “There’s no doubt that these therapeutic agents are effective,” and continued follow-up will clarify their comparative efficacy, he concluded.
SOURCES: Day JW, et al. AAN 2020. Abstract S27.001. Mendell JR, et al. AAN 2020. Abstract S27.002. Strauss KA, et al. AAN 2020. Abstract S27.003.
FROM AAN 2020
Video coaching may relieve anxiety and distress for long-distance cancer caregivers
Anxiety and distress related to caring for a cancer patient who lives far away may be alleviated through an intervention that includes video-based coaching sessions with a nurse practitioner or social worker, a randomized study suggests.
About 20% of long-distance caregivers had a significant reduction in anxiety and 25% had a significant reduction in distress when they received video coaching sessions, attended oncologist visits via video, and had access to a website specifically designed for their needs.
Adding the caregiver to oncologist office visits made the patients feel better supported and didn’t add a significant amount of time to the encounter, said Sara L. Douglas, PhD, RN, of Case Western Reserve University, Cleveland.
Taken together, these results suggest that fairly simple technologies can be leveraged to help caregivers cope with psychological strains related to supporting a patient who doesn’t live nearby, Dr. Douglas said.
Distance caregivers, defined as those who live an hour or more away from the patient, can experience high rates of distress and anxiety because they lack first-hand information or may have uncertainty about the patient’s current condition, according to Dr. Douglas and colleagues.
“Caregivers’ high rates of anxiety and distress have been found to have a negative impact not only upon their own health but upon their ability to provide high quality care to the patient,” Dr. Douglas said.
With this in mind, she and her colleagues conducted a 4-month study of distance caregivers. Dr. Douglas presented results from the study at the American Society of Clinical Oncology virtual scientific program during a press briefing in advance of the meeting. This year, ASCO’s annual meeting is split into two parts. The virtual scientific program will be presented online on May 29-31, and the virtual education program will be available Aug. 8-10.
Study details
The study enrolled 441 distance caregivers of cancer patients, and Dr. Douglas presented results in 311 of those caregivers. (Data in the presentation differ from the abstract.) The caregivers were, on average, 47 years of age. Most were female (72%), white (67%), the child of the patient (63%), currently employed (81%), and new to the distance caregiver role (89%).
The caregivers were randomized to one of three study arms.
One arm received the full intervention, which consisted of four video-coaching sessions with an advanced practice nurse or social worker, videoconference office visits with the physician and patient, and access to a website with information for cancer distance caregivers. A second arm received no video coaching but had access to the website and participated in video visits with the physician and patient. The third arm, which only received access to the website, served as the study’s control group.
Results
Dr. Douglas said that the full intervention had the biggest impact on caregivers’ distress and anxiety.
Among distance caregivers who received the full intervention, 19.2% had a significant reduction in anxiety (P = .03), as measured in online surveys before and after the intervention using the PROMIS Anxiety instrument. Furthermore, 24.8% of these caregivers had a significant reduction in distress (P = .02) from preintervention to post intervention, as measured by the National Comprehensive Cancer Network Distress Thermometer. Overall, distress and anxiety scores decreased in this arm.
Distance caregivers who only had physician-patient video visits and website access had a “moderate” reduction in distress and anxiety, Dr. Douglas said. Among these caregivers, 17.3% had an improvement in anxiety from baseline, and 19.8% had an improvement in distress. Overall, distress scores decreased, but anxiety scores increased slightly in this arm.
In the control arm, 13.1% of caregivers had an improvement in anxiety from baseline, and 18% had an improvement in distress. Overall, both anxiety and distress scores increased in this arm.
“While the full intervention yielded the best results for distance caregivers, we recognize that not all health care systems have the resources to provide individualized coaching sessions to distance caregivers,” Dr. Douglas said. “Therefore, it is worth noting that videoconference office visits alone are found to be of some benefit in improving distress and anxiety in this group of cancer caregivers.”
The study results suggest videoconferencing interventions can improve the emotional well-being of remote caregivers who provide “critical support” for cancer patients, said ASCO President Howard A. “Skip” Burris III, MD.
“As COVID-19 forces separation from loved ones and increases anxiety for people with cancer and their caregivers, providing emotional support virtually is more important than ever,” Dr. Burris said in a news release highlighting the study.
This study was funded by the National Institutes of Health and Case Comprehensive Cancer Center. Dr. Douglas reported having no disclosures. Other researchers involved in the study disclosed relationships with BridgeBio Pharma, Cardinal Health, Apexigen, Roche/Genentech, Seattle Genetics, Tesaro, Array BioPharma, Abbvie, Bristol-Myers Squibb, and Celgene. A full list of Dr. Burris’s financial disclosures is available on the ASCO website.
SOURCE: Douglas SL et al. ASCO 2020, Abstract 12123.
Anxiety and distress related to caring for a cancer patient who lives far away may be alleviated through an intervention that includes video-based coaching sessions with a nurse practitioner or social worker, a randomized study suggests.
About 20% of long-distance caregivers had a significant reduction in anxiety and 25% had a significant reduction in distress when they received video coaching sessions, attended oncologist visits via video, and had access to a website specifically designed for their needs.
Adding the caregiver to oncologist office visits made the patients feel better supported and didn’t add a significant amount of time to the encounter, said Sara L. Douglas, PhD, RN, of Case Western Reserve University, Cleveland.
Taken together, these results suggest that fairly simple technologies can be leveraged to help caregivers cope with psychological strains related to supporting a patient who doesn’t live nearby, Dr. Douglas said.
Distance caregivers, defined as those who live an hour or more away from the patient, can experience high rates of distress and anxiety because they lack first-hand information or may have uncertainty about the patient’s current condition, according to Dr. Douglas and colleagues.
“Caregivers’ high rates of anxiety and distress have been found to have a negative impact not only upon their own health but upon their ability to provide high quality care to the patient,” Dr. Douglas said.
With this in mind, she and her colleagues conducted a 4-month study of distance caregivers. Dr. Douglas presented results from the study at the American Society of Clinical Oncology virtual scientific program during a press briefing in advance of the meeting. This year, ASCO’s annual meeting is split into two parts. The virtual scientific program will be presented online on May 29-31, and the virtual education program will be available Aug. 8-10.
Study details
The study enrolled 441 distance caregivers of cancer patients, and Dr. Douglas presented results in 311 of those caregivers. (Data in the presentation differ from the abstract.) The caregivers were, on average, 47 years of age. Most were female (72%), white (67%), the child of the patient (63%), currently employed (81%), and new to the distance caregiver role (89%).
The caregivers were randomized to one of three study arms.
One arm received the full intervention, which consisted of four video-coaching sessions with an advanced practice nurse or social worker, videoconference office visits with the physician and patient, and access to a website with information for cancer distance caregivers. A second arm received no video coaching but had access to the website and participated in video visits with the physician and patient. The third arm, which only received access to the website, served as the study’s control group.
Results
Dr. Douglas said that the full intervention had the biggest impact on caregivers’ distress and anxiety.
Among distance caregivers who received the full intervention, 19.2% had a significant reduction in anxiety (P = .03), as measured in online surveys before and after the intervention using the PROMIS Anxiety instrument. Furthermore, 24.8% of these caregivers had a significant reduction in distress (P = .02) from preintervention to post intervention, as measured by the National Comprehensive Cancer Network Distress Thermometer. Overall, distress and anxiety scores decreased in this arm.
Distance caregivers who only had physician-patient video visits and website access had a “moderate” reduction in distress and anxiety, Dr. Douglas said. Among these caregivers, 17.3% had an improvement in anxiety from baseline, and 19.8% had an improvement in distress. Overall, distress scores decreased, but anxiety scores increased slightly in this arm.
In the control arm, 13.1% of caregivers had an improvement in anxiety from baseline, and 18% had an improvement in distress. Overall, both anxiety and distress scores increased in this arm.
“While the full intervention yielded the best results for distance caregivers, we recognize that not all health care systems have the resources to provide individualized coaching sessions to distance caregivers,” Dr. Douglas said. “Therefore, it is worth noting that videoconference office visits alone are found to be of some benefit in improving distress and anxiety in this group of cancer caregivers.”
The study results suggest videoconferencing interventions can improve the emotional well-being of remote caregivers who provide “critical support” for cancer patients, said ASCO President Howard A. “Skip” Burris III, MD.
“As COVID-19 forces separation from loved ones and increases anxiety for people with cancer and their caregivers, providing emotional support virtually is more important than ever,” Dr. Burris said in a news release highlighting the study.
This study was funded by the National Institutes of Health and Case Comprehensive Cancer Center. Dr. Douglas reported having no disclosures. Other researchers involved in the study disclosed relationships with BridgeBio Pharma, Cardinal Health, Apexigen, Roche/Genentech, Seattle Genetics, Tesaro, Array BioPharma, Abbvie, Bristol-Myers Squibb, and Celgene. A full list of Dr. Burris’s financial disclosures is available on the ASCO website.
SOURCE: Douglas SL et al. ASCO 2020, Abstract 12123.
Anxiety and distress related to caring for a cancer patient who lives far away may be alleviated through an intervention that includes video-based coaching sessions with a nurse practitioner or social worker, a randomized study suggests.
About 20% of long-distance caregivers had a significant reduction in anxiety and 25% had a significant reduction in distress when they received video coaching sessions, attended oncologist visits via video, and had access to a website specifically designed for their needs.
Adding the caregiver to oncologist office visits made the patients feel better supported and didn’t add a significant amount of time to the encounter, said Sara L. Douglas, PhD, RN, of Case Western Reserve University, Cleveland.
Taken together, these results suggest that fairly simple technologies can be leveraged to help caregivers cope with psychological strains related to supporting a patient who doesn’t live nearby, Dr. Douglas said.
Distance caregivers, defined as those who live an hour or more away from the patient, can experience high rates of distress and anxiety because they lack first-hand information or may have uncertainty about the patient’s current condition, according to Dr. Douglas and colleagues.
“Caregivers’ high rates of anxiety and distress have been found to have a negative impact not only upon their own health but upon their ability to provide high quality care to the patient,” Dr. Douglas said.
With this in mind, she and her colleagues conducted a 4-month study of distance caregivers. Dr. Douglas presented results from the study at the American Society of Clinical Oncology virtual scientific program during a press briefing in advance of the meeting. This year, ASCO’s annual meeting is split into two parts. The virtual scientific program will be presented online on May 29-31, and the virtual education program will be available Aug. 8-10.
Study details
The study enrolled 441 distance caregivers of cancer patients, and Dr. Douglas presented results in 311 of those caregivers. (Data in the presentation differ from the abstract.) The caregivers were, on average, 47 years of age. Most were female (72%), white (67%), the child of the patient (63%), currently employed (81%), and new to the distance caregiver role (89%).
The caregivers were randomized to one of three study arms.
One arm received the full intervention, which consisted of four video-coaching sessions with an advanced practice nurse or social worker, videoconference office visits with the physician and patient, and access to a website with information for cancer distance caregivers. A second arm received no video coaching but had access to the website and participated in video visits with the physician and patient. The third arm, which only received access to the website, served as the study’s control group.
Results
Dr. Douglas said that the full intervention had the biggest impact on caregivers’ distress and anxiety.
Among distance caregivers who received the full intervention, 19.2% had a significant reduction in anxiety (P = .03), as measured in online surveys before and after the intervention using the PROMIS Anxiety instrument. Furthermore, 24.8% of these caregivers had a significant reduction in distress (P = .02) from preintervention to post intervention, as measured by the National Comprehensive Cancer Network Distress Thermometer. Overall, distress and anxiety scores decreased in this arm.
Distance caregivers who only had physician-patient video visits and website access had a “moderate” reduction in distress and anxiety, Dr. Douglas said. Among these caregivers, 17.3% had an improvement in anxiety from baseline, and 19.8% had an improvement in distress. Overall, distress scores decreased, but anxiety scores increased slightly in this arm.
In the control arm, 13.1% of caregivers had an improvement in anxiety from baseline, and 18% had an improvement in distress. Overall, both anxiety and distress scores increased in this arm.
“While the full intervention yielded the best results for distance caregivers, we recognize that not all health care systems have the resources to provide individualized coaching sessions to distance caregivers,” Dr. Douglas said. “Therefore, it is worth noting that videoconference office visits alone are found to be of some benefit in improving distress and anxiety in this group of cancer caregivers.”
The study results suggest videoconferencing interventions can improve the emotional well-being of remote caregivers who provide “critical support” for cancer patients, said ASCO President Howard A. “Skip” Burris III, MD.
“As COVID-19 forces separation from loved ones and increases anxiety for people with cancer and their caregivers, providing emotional support virtually is more important than ever,” Dr. Burris said in a news release highlighting the study.
This study was funded by the National Institutes of Health and Case Comprehensive Cancer Center. Dr. Douglas reported having no disclosures. Other researchers involved in the study disclosed relationships with BridgeBio Pharma, Cardinal Health, Apexigen, Roche/Genentech, Seattle Genetics, Tesaro, Array BioPharma, Abbvie, Bristol-Myers Squibb, and Celgene. A full list of Dr. Burris’s financial disclosures is available on the ASCO website.
SOURCE: Douglas SL et al. ASCO 2020, Abstract 12123.
FROM ASCO 2020