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Adults with cancer experienced significant reductions in pain after taking medicinal cannabis, in a study.

Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.

However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.

In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.

The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.

Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.

Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).

Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).

“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.

In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.

Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.

Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.

The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.

The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.

The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.

Adults with cancer experienced significant reductions in pain after taking medicinal cannabis, in a study.

Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.

However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.

In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.

The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.

Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.

Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).

Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).

“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.

In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.

Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.

Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.

The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.

The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.

The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.

Adults with cancer experienced significant reductions in pain after taking medicinal cannabis, in a study.

Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.

However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.

In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.

The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.

Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.

Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).

Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).

“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.

In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.

Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.

Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.

The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.

The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.

The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.

NEW YORK – In a blood cancer conference session – “Will autologous stem cell transplant (ASCT) continue to be the standard of care (SoC) in frontline therapy for multiple myeloma (MM)?” – two experts weighed in on the merits of their approaches to treating MM at the Great Debates and Updates Hematologic Malignancies conference.

Hematologist-oncologists whose top priority is ensuring that patients have the best chance of progression-free survival (PFS) will continue to choose ASCT as a best practice, argued Amrita Krishnan, MD, hematologist at the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, Calif.

credit Dr. Landgren

A differing perspective was presented by C. Ola Landgren, MD, PhD, hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami. Dr. Landgren cited evidence that, for newly diagnosed MM patients treated successfully with modern combination therapies, ASCT is not a mandatory treatment step before starting maintenance therapy. 

Making a case for ASCT as the SoC, Dr. Krishnan noted, “based on the DETERMINATION trial [DT], there is far superior rate of PFS with patients who get ASCT up front, compared patients who got only conventional chemotherapy with lenalidomide, bortezomib, and dexamethasone [RVd]. PFS is the endpoint we look for in our treatment regimens.

“If you don’t use ASCT up front, you may lose the opportunity at later relapse. This is not to say that transplant is the only tool at our disposal. It is just an indispensable one. The GRIFFIN trial [GT] has shown us that robust combinations of drugs [both RVd and dexamethasone +RVd] can improve patient outcomes both before and after ASCT,” Dr. Krishnan concluded.

In his presentation, Dr. Landgren stated that, in the DT, while PFS is prolonged by the addition of ASCT to RVd, adding ASCT did not significantly increase overall survival (OS) rates. He added that treatment-related AEs of grade 3+ occurred in only 78.2% of patients on RVd versus 94.2% of RVd + ASCT patients.

“ASCT should not be the SoC frontline treatment in MM because it does not prolong OS. The IFM trial and the DT both show that there is no difference in OS between drug combination therapy followed by transplant and maintenance versus combination therapy alone, followed by transplant and maintenance. Furthermore, patients who get ASCT have higher risk of developing secondary malignancies, worse quality of life, and higher long-term morbidity with other conditions,” Dr. Landgren said.

He cited the MAIA trial administered daratumumab and lenalidomide plus dexamethasone (DRd) to patients who were too old or too frail to qualify for ASCT. Over half of patients in the DRd arm of MAIA had an estimated progression-free survival rate at 60 months.

“Furthermore, GT and the MANHATTAN clinical trials showed that we can safely add CD38-targeted monoclonal antibodies to standard combination therapies [lenalidomide, bortezomib, and dexamethasone (KRd)], resulting in higher rates of minimal-residual-disease (MRD) negativity. That means modern four-drug combination therapies [DR-RVd and DR-KRd] will allow more [and more newly diagnosed] MM patients to achieve MRD negativity in the absence of ASCT,” Dr. Landgren concluded.

courtesy of Dr. Richter

Asked to comment on the two viewpoints, Joshua Richter, MD, director of myeloma treatment at the Blavatnik Family Center at Chelsea Mount Sinai, New York, said: “With some patients, we can get similar outcomes, whether or not we do a transplant. Doctors need to be better at choosing who really needs ASCT. Older people with standard-risk disease or people who achieve MRD-negative status after pharmacological treatment might not need to receive a transplant as much as those who have bulk disease or high-risk cytogenetics.

“Although ASCT might not be the best frontline option for everyone, collecting cells from most patients and storing them has many advantages. It allows us to do have the option of ASCT in later lines of therapy. In some patients with low blood counts, we can use stored cells to reboot their marrow and make them eligible for trials of promising new drugs,” Dr. Richter said.

Dr. Krishnan disclosed relationships with Takeda, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi, Pfizer, Adaptive, Regeneron, Janssen, AstraZeneca, Artiva, and Sutro. Dr. Landgren reported ties with Amgen, BMS, Celgene, Janssen, Takedam Glenmark, Juno, Pfizer, Merck, and others. Dr. Richter disclosed relationships with Janssen, BMS, and Takeda.

NEW YORK – In a blood cancer conference session – “Will autologous stem cell transplant (ASCT) continue to be the standard of care (SoC) in frontline therapy for multiple myeloma (MM)?” – two experts weighed in on the merits of their approaches to treating MM at the Great Debates and Updates Hematologic Malignancies conference.

Hematologist-oncologists whose top priority is ensuring that patients have the best chance of progression-free survival (PFS) will continue to choose ASCT as a best practice, argued Amrita Krishnan, MD, hematologist at the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, Calif.

credit Dr. Landgren

A differing perspective was presented by C. Ola Landgren, MD, PhD, hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami. Dr. Landgren cited evidence that, for newly diagnosed MM patients treated successfully with modern combination therapies, ASCT is not a mandatory treatment step before starting maintenance therapy. 

Making a case for ASCT as the SoC, Dr. Krishnan noted, “based on the DETERMINATION trial [DT], there is far superior rate of PFS with patients who get ASCT up front, compared patients who got only conventional chemotherapy with lenalidomide, bortezomib, and dexamethasone [RVd]. PFS is the endpoint we look for in our treatment regimens.

“If you don’t use ASCT up front, you may lose the opportunity at later relapse. This is not to say that transplant is the only tool at our disposal. It is just an indispensable one. The GRIFFIN trial [GT] has shown us that robust combinations of drugs [both RVd and dexamethasone +RVd] can improve patient outcomes both before and after ASCT,” Dr. Krishnan concluded.

In his presentation, Dr. Landgren stated that, in the DT, while PFS is prolonged by the addition of ASCT to RVd, adding ASCT did not significantly increase overall survival (OS) rates. He added that treatment-related AEs of grade 3+ occurred in only 78.2% of patients on RVd versus 94.2% of RVd + ASCT patients.

“ASCT should not be the SoC frontline treatment in MM because it does not prolong OS. The IFM trial and the DT both show that there is no difference in OS between drug combination therapy followed by transplant and maintenance versus combination therapy alone, followed by transplant and maintenance. Furthermore, patients who get ASCT have higher risk of developing secondary malignancies, worse quality of life, and higher long-term morbidity with other conditions,” Dr. Landgren said.

He cited the MAIA trial administered daratumumab and lenalidomide plus dexamethasone (DRd) to patients who were too old or too frail to qualify for ASCT. Over half of patients in the DRd arm of MAIA had an estimated progression-free survival rate at 60 months.

“Furthermore, GT and the MANHATTAN clinical trials showed that we can safely add CD38-targeted monoclonal antibodies to standard combination therapies [lenalidomide, bortezomib, and dexamethasone (KRd)], resulting in higher rates of minimal-residual-disease (MRD) negativity. That means modern four-drug combination therapies [DR-RVd and DR-KRd] will allow more [and more newly diagnosed] MM patients to achieve MRD negativity in the absence of ASCT,” Dr. Landgren concluded.

courtesy of Dr. Richter

Asked to comment on the two viewpoints, Joshua Richter, MD, director of myeloma treatment at the Blavatnik Family Center at Chelsea Mount Sinai, New York, said: “With some patients, we can get similar outcomes, whether or not we do a transplant. Doctors need to be better at choosing who really needs ASCT. Older people with standard-risk disease or people who achieve MRD-negative status after pharmacological treatment might not need to receive a transplant as much as those who have bulk disease or high-risk cytogenetics.

“Although ASCT might not be the best frontline option for everyone, collecting cells from most patients and storing them has many advantages. It allows us to do have the option of ASCT in later lines of therapy. In some patients with low blood counts, we can use stored cells to reboot their marrow and make them eligible for trials of promising new drugs,” Dr. Richter said.

Dr. Krishnan disclosed relationships with Takeda, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi, Pfizer, Adaptive, Regeneron, Janssen, AstraZeneca, Artiva, and Sutro. Dr. Landgren reported ties with Amgen, BMS, Celgene, Janssen, Takedam Glenmark, Juno, Pfizer, Merck, and others. Dr. Richter disclosed relationships with Janssen, BMS, and Takeda.

NEW YORK – In a blood cancer conference session – “Will autologous stem cell transplant (ASCT) continue to be the standard of care (SoC) in frontline therapy for multiple myeloma (MM)?” – two experts weighed in on the merits of their approaches to treating MM at the Great Debates and Updates Hematologic Malignancies conference.

Hematologist-oncologists whose top priority is ensuring that patients have the best chance of progression-free survival (PFS) will continue to choose ASCT as a best practice, argued Amrita Krishnan, MD, hematologist at the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, Calif.

credit Dr. Landgren

A differing perspective was presented by C. Ola Landgren, MD, PhD, hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami. Dr. Landgren cited evidence that, for newly diagnosed MM patients treated successfully with modern combination therapies, ASCT is not a mandatory treatment step before starting maintenance therapy. 

Making a case for ASCT as the SoC, Dr. Krishnan noted, “based on the DETERMINATION trial [DT], there is far superior rate of PFS with patients who get ASCT up front, compared patients who got only conventional chemotherapy with lenalidomide, bortezomib, and dexamethasone [RVd]. PFS is the endpoint we look for in our treatment regimens.

“If you don’t use ASCT up front, you may lose the opportunity at later relapse. This is not to say that transplant is the only tool at our disposal. It is just an indispensable one. The GRIFFIN trial [GT] has shown us that robust combinations of drugs [both RVd and dexamethasone +RVd] can improve patient outcomes both before and after ASCT,” Dr. Krishnan concluded.

In his presentation, Dr. Landgren stated that, in the DT, while PFS is prolonged by the addition of ASCT to RVd, adding ASCT did not significantly increase overall survival (OS) rates. He added that treatment-related AEs of grade 3+ occurred in only 78.2% of patients on RVd versus 94.2% of RVd + ASCT patients.

“ASCT should not be the SoC frontline treatment in MM because it does not prolong OS. The IFM trial and the DT both show that there is no difference in OS between drug combination therapy followed by transplant and maintenance versus combination therapy alone, followed by transplant and maintenance. Furthermore, patients who get ASCT have higher risk of developing secondary malignancies, worse quality of life, and higher long-term morbidity with other conditions,” Dr. Landgren said.

He cited the MAIA trial administered daratumumab and lenalidomide plus dexamethasone (DRd) to patients who were too old or too frail to qualify for ASCT. Over half of patients in the DRd arm of MAIA had an estimated progression-free survival rate at 60 months.

“Furthermore, GT and the MANHATTAN clinical trials showed that we can safely add CD38-targeted monoclonal antibodies to standard combination therapies [lenalidomide, bortezomib, and dexamethasone (KRd)], resulting in higher rates of minimal-residual-disease (MRD) negativity. That means modern four-drug combination therapies [DR-RVd and DR-KRd] will allow more [and more newly diagnosed] MM patients to achieve MRD negativity in the absence of ASCT,” Dr. Landgren concluded.

courtesy of Dr. Richter

Asked to comment on the two viewpoints, Joshua Richter, MD, director of myeloma treatment at the Blavatnik Family Center at Chelsea Mount Sinai, New York, said: “With some patients, we can get similar outcomes, whether or not we do a transplant. Doctors need to be better at choosing who really needs ASCT. Older people with standard-risk disease or people who achieve MRD-negative status after pharmacological treatment might not need to receive a transplant as much as those who have bulk disease or high-risk cytogenetics.

“Although ASCT might not be the best frontline option for everyone, collecting cells from most patients and storing them has many advantages. It allows us to do have the option of ASCT in later lines of therapy. In some patients with low blood counts, we can use stored cells to reboot their marrow and make them eligible for trials of promising new drugs,” Dr. Richter said.

Dr. Krishnan disclosed relationships with Takeda, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi, Pfizer, Adaptive, Regeneron, Janssen, AstraZeneca, Artiva, and Sutro. Dr. Landgren reported ties with Amgen, BMS, Celgene, Janssen, Takedam Glenmark, Juno, Pfizer, Merck, and others. Dr. Richter disclosed relationships with Janssen, BMS, and Takeda.

The U.S. government plans to no longer require federal workers or international air travelers to be vaccinated for COVID-19, the Biden administration has announced. 

The move means vaccines will no longer be required for workers who are federal employees, federal contractors, Head Start early education employees, workers at Medicare-certified health care facilities, and those who work at U.S. borders. International air travelers will no longer be required to prove their vaccination status. The requirement will be lifted at the end of the day on May 11, which is also when the federal public health emergency declaration ends.

“While vaccination remains one of the most important tools in advancing the health and safety of employees and promoting the efficiency of workplaces, we are now in a different phase of our response when these measures are no longer necessary,” an announcement from the White House stated.

White House officials credited vaccine requirements with saving millions of lives, noting that the rules ensured “the safety of workers in critical workforces including those in the healthcare and education sectors, protecting themselves and the populations they serve, and strengthening their ability to provide services without disruptions to operations.”

More than 100 million people were subject to the vaccine requirement, The Associated Press reported. All but 2% of those covered by the mandate had received at least one dose or had a pending or approved exception on file by January 2022, the Biden administration said, noting that COVID deaths have dropped 95% since January 2021 and hospitalizations are down nearly 91%.

In January, vaccine requirements were lifted for U.S. military members.

On the government-run website Safer Federal Workforce, which helped affected organizations put federal COVID rules into place, agencies were told to “take no action to implement or enforce the COVID-19 vaccination requirement” at this time.

A version of this article first appeared on WebMD.com.

The U.S. government plans to no longer require federal workers or international air travelers to be vaccinated for COVID-19, the Biden administration has announced. 

The move means vaccines will no longer be required for workers who are federal employees, federal contractors, Head Start early education employees, workers at Medicare-certified health care facilities, and those who work at U.S. borders. International air travelers will no longer be required to prove their vaccination status. The requirement will be lifted at the end of the day on May 11, which is also when the federal public health emergency declaration ends.

“While vaccination remains one of the most important tools in advancing the health and safety of employees and promoting the efficiency of workplaces, we are now in a different phase of our response when these measures are no longer necessary,” an announcement from the White House stated.

White House officials credited vaccine requirements with saving millions of lives, noting that the rules ensured “the safety of workers in critical workforces including those in the healthcare and education sectors, protecting themselves and the populations they serve, and strengthening their ability to provide services without disruptions to operations.”

More than 100 million people were subject to the vaccine requirement, The Associated Press reported. All but 2% of those covered by the mandate had received at least one dose or had a pending or approved exception on file by January 2022, the Biden administration said, noting that COVID deaths have dropped 95% since January 2021 and hospitalizations are down nearly 91%.

In January, vaccine requirements were lifted for U.S. military members.

On the government-run website Safer Federal Workforce, which helped affected organizations put federal COVID rules into place, agencies were told to “take no action to implement or enforce the COVID-19 vaccination requirement” at this time.

A version of this article first appeared on WebMD.com.

The U.S. government plans to no longer require federal workers or international air travelers to be vaccinated for COVID-19, the Biden administration has announced. 

The move means vaccines will no longer be required for workers who are federal employees, federal contractors, Head Start early education employees, workers at Medicare-certified health care facilities, and those who work at U.S. borders. International air travelers will no longer be required to prove their vaccination status. The requirement will be lifted at the end of the day on May 11, which is also when the federal public health emergency declaration ends.

“While vaccination remains one of the most important tools in advancing the health and safety of employees and promoting the efficiency of workplaces, we are now in a different phase of our response when these measures are no longer necessary,” an announcement from the White House stated.

White House officials credited vaccine requirements with saving millions of lives, noting that the rules ensured “the safety of workers in critical workforces including those in the healthcare and education sectors, protecting themselves and the populations they serve, and strengthening their ability to provide services without disruptions to operations.”

More than 100 million people were subject to the vaccine requirement, The Associated Press reported. All but 2% of those covered by the mandate had received at least one dose or had a pending or approved exception on file by January 2022, the Biden administration said, noting that COVID deaths have dropped 95% since January 2021 and hospitalizations are down nearly 91%.

In January, vaccine requirements were lifted for U.S. military members.

On the government-run website Safer Federal Workforce, which helped affected organizations put federal COVID rules into place, agencies were told to “take no action to implement or enforce the COVID-19 vaccination requirement” at this time.

A version of this article first appeared on WebMD.com.

Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do. 

In an article published in Cell, cancer specialists from across the globe provided their take on the big questions worth exploring in research over the coming years.

More sex-specific research

Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.

Dr. Loi’s recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.

“It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting,” Dr. Loi said. 
 

The global cancer community

C. S. Pramesh, MMBS, MS, FRCS, director of Tata Memorial Hospital in Mumbai, India, said that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.

“With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries,” Dr. Pramesh said. “Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world.”

Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed “cancer groundshot.”

Dr. Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research – goals that are critical but often not prioritized by high-income countries or industry, he said.

“Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good,” Dr. Pramesh said.
 

Prioritizing combination therapies

The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, of The Netherlands Cancer Institute.

“Resistance to therapy remains a major obstacle in the treatment of cancer,” Dr. Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with “nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic.”

A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma. 

“I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets,” he said. “Over time, this would also contribute to affordable health care through use of more generic drugs.”
 

Cancer drugs and the heart

Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Dr. Moslehi discovered that “many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship.”

But, Dr. Moslehi explained, “we are entering [uncharted] waters.”

Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Dr. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.

“Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation,” Dr. Moslehi explained.
 

Inside rare cancers

William Sellers, MD, director of the Broad Institute of MIT’s Cancer Program, Cambridge, Mass., said rare cancers should be the next focus.

After all, “rare cancers are only rare in isolation,” Dr. Sellers said, noting that these cancers make up 20%-24% of all cancer diagnoses.

Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers. 

“New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases,” he said. 

The researchers reported numerous relationships with pharmaceutical companies.
 

A version of this article first appeared on Medscape.com.

Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do. 

In an article published in Cell, cancer specialists from across the globe provided their take on the big questions worth exploring in research over the coming years.

More sex-specific research

Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.

Dr. Loi’s recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.

“It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting,” Dr. Loi said. 
 

The global cancer community

C. S. Pramesh, MMBS, MS, FRCS, director of Tata Memorial Hospital in Mumbai, India, said that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.

“With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries,” Dr. Pramesh said. “Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world.”

Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed “cancer groundshot.”

Dr. Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research – goals that are critical but often not prioritized by high-income countries or industry, he said.

“Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good,” Dr. Pramesh said.
 

Prioritizing combination therapies

The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, of The Netherlands Cancer Institute.

“Resistance to therapy remains a major obstacle in the treatment of cancer,” Dr. Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with “nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic.”

A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma. 

“I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets,” he said. “Over time, this would also contribute to affordable health care through use of more generic drugs.”
 

Cancer drugs and the heart

Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Dr. Moslehi discovered that “many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship.”

But, Dr. Moslehi explained, “we are entering [uncharted] waters.”

Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Dr. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.

“Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation,” Dr. Moslehi explained.
 

Inside rare cancers

William Sellers, MD, director of the Broad Institute of MIT’s Cancer Program, Cambridge, Mass., said rare cancers should be the next focus.

After all, “rare cancers are only rare in isolation,” Dr. Sellers said, noting that these cancers make up 20%-24% of all cancer diagnoses.

Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers. 

“New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases,” he said. 

The researchers reported numerous relationships with pharmaceutical companies.
 

A version of this article first appeared on Medscape.com.

Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do. 

In an article published in Cell, cancer specialists from across the globe provided their take on the big questions worth exploring in research over the coming years.

More sex-specific research

Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.

Dr. Loi’s recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.

“It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting,” Dr. Loi said. 
 

The global cancer community

C. S. Pramesh, MMBS, MS, FRCS, director of Tata Memorial Hospital in Mumbai, India, said that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.

“With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries,” Dr. Pramesh said. “Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world.”

Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed “cancer groundshot.”

Dr. Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research – goals that are critical but often not prioritized by high-income countries or industry, he said.

“Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good,” Dr. Pramesh said.
 

Prioritizing combination therapies

The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, of The Netherlands Cancer Institute.

“Resistance to therapy remains a major obstacle in the treatment of cancer,” Dr. Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with “nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic.”

A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma. 

“I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets,” he said. “Over time, this would also contribute to affordable health care through use of more generic drugs.”
 

Cancer drugs and the heart

Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Dr. Moslehi discovered that “many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship.”

But, Dr. Moslehi explained, “we are entering [uncharted] waters.”

Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Dr. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.

“Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation,” Dr. Moslehi explained.
 

Inside rare cancers

William Sellers, MD, director of the Broad Institute of MIT’s Cancer Program, Cambridge, Mass., said rare cancers should be the next focus.

After all, “rare cancers are only rare in isolation,” Dr. Sellers said, noting that these cancers make up 20%-24% of all cancer diagnoses.

Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers. 

“New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases,” he said. 

The researchers reported numerous relationships with pharmaceutical companies.
 

A version of this article first appeared on Medscape.com.

An old dog – nitrous oxide – can learn new tricks, managing pain in men undergoing transrectal biopsies, researchers reported at the annual meeting of the American Urological Association.

“At concentrations of less than 50%, nitrous oxide is classified as a minimal sedative, making it a promising option for many urologic outpatient procedures such as prostate biopsies,” said Heidi Rayala, MD, PhD, assistant professor of surgery at Harvard Medical School, Boston, who helped conduct the study.

Nitrous oxide is best known as a pain medication and anesthetic during dental procedures and childbirth, after trauma, and in end-of-life care.

In the new study, Dr. Rayala and her colleagues at Harvard and Beth Israel-Deaconess Medical Center, Boston, randomly assigned 128 men to self-administered nitrous oxide (SANO) or oxygen as a placebo. Patients in the SANO group had a smaller change in post-biopsy pain score (Visual Analog Scale for pain, 0.43 vs. 1.03; P = .03) and lower odds of experiencing pain during the procedure (odds ratio, 0.45; confidence interval, 0.21-0.97; P = .04).

A comparison of anxiety scores in the two groups failed to find a statistically significant difference between SANO and placebo. However, more men who received nitrous oxide said they tolerated the procedure “better than expected” (61% vs. 41%; P = 0.02), according to the researchers.

Dr. Rayala said that the researchers used the Nitrouseal system (Sedation Systems), in which the patient holds a mask to their face and works with staff to adjust the gas levels to the desired amount. The system is governed to max out at 50% nitrous oxide, ensuring “minimal sedation concentrations, so anesthesia personnel are not required,” she said.

“At levels of less than 50%, patients respond normally to verbal commands and maintain normal airway reflexes,” Dr. Rayala added. “This provides an advantage in that patients do not require the presence of anesthesia personnel.” And because the body eliminates the gas within about 5 minutes, patients do not require an escort home, she said.

This system is also self-scavenging to protect the operating urologist and other personnel from environmental exposure to nitrous oxide.

Dr. Rayala said that three patients (2.3%) found the mask uncomfortable, but in follow-up studies the clinicians have done a better job of preparing patients for the feeling of the mask, making a marked difference. Headaches and nausea are the most commonly reported complaints at concentrations above 50%.

“We did not have patients report headaches or nausea in new study (by the BIDMC group),” she said. This study has been submitted for publication.

Clinicians outside the United States have been quicker to embrace nitrous oxide for prostate procedures.

In a randomized controlled trial, researchers in Australia found no significant improvement in pain scores at 15 minutes from the use of nitrous oxide during transrectal biopsies; however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

Stephen McCombie, MD, a consultant at Perth Urology Clinic, Australia, who has been adapting the nitrous oxide protocol for transrectal biopsies to transperineal procedures, said that the Beth Israel study “adds to the evidence to support adjunct use of mild inhalational anesthetics and analgesics during prostate biopsies to improve the patient experience of the procedure.”

He said that the role for these agents may grow with the global trend away from transrectal prostate biopsies and toward transperineal biopsies, largely driven by increasing rates of sepsis after transrectal biopsies.

“While transperineal biopsies can be more painful then transrectal biopsies when performed under local anesthesia, perhaps due to biopsies being taken through the highly sensate perineum as opposed to above the dentate line, optimization of the technique can significantly reduce the discomfort associated with the procedure, which may be further reduced with these agents,” Dr. McCombie said.

“Studies indicate that transperineal biopsies can be more painful than the traditional transrectal biopsies,” Dr. Rayala said. “We do offer transperineal biopsies at BIDMC, and we are gearing up to repeat the SANO study” for those patients.

Dr. Rayala and Dr. McCombie have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An old dog – nitrous oxide – can learn new tricks, managing pain in men undergoing transrectal biopsies, researchers reported at the annual meeting of the American Urological Association.

“At concentrations of less than 50%, nitrous oxide is classified as a minimal sedative, making it a promising option for many urologic outpatient procedures such as prostate biopsies,” said Heidi Rayala, MD, PhD, assistant professor of surgery at Harvard Medical School, Boston, who helped conduct the study.

Nitrous oxide is best known as a pain medication and anesthetic during dental procedures and childbirth, after trauma, and in end-of-life care.

In the new study, Dr. Rayala and her colleagues at Harvard and Beth Israel-Deaconess Medical Center, Boston, randomly assigned 128 men to self-administered nitrous oxide (SANO) or oxygen as a placebo. Patients in the SANO group had a smaller change in post-biopsy pain score (Visual Analog Scale for pain, 0.43 vs. 1.03; P = .03) and lower odds of experiencing pain during the procedure (odds ratio, 0.45; confidence interval, 0.21-0.97; P = .04).

A comparison of anxiety scores in the two groups failed to find a statistically significant difference between SANO and placebo. However, more men who received nitrous oxide said they tolerated the procedure “better than expected” (61% vs. 41%; P = 0.02), according to the researchers.

Dr. Rayala said that the researchers used the Nitrouseal system (Sedation Systems), in which the patient holds a mask to their face and works with staff to adjust the gas levels to the desired amount. The system is governed to max out at 50% nitrous oxide, ensuring “minimal sedation concentrations, so anesthesia personnel are not required,” she said.

“At levels of less than 50%, patients respond normally to verbal commands and maintain normal airway reflexes,” Dr. Rayala added. “This provides an advantage in that patients do not require the presence of anesthesia personnel.” And because the body eliminates the gas within about 5 minutes, patients do not require an escort home, she said.

This system is also self-scavenging to protect the operating urologist and other personnel from environmental exposure to nitrous oxide.

Dr. Rayala said that three patients (2.3%) found the mask uncomfortable, but in follow-up studies the clinicians have done a better job of preparing patients for the feeling of the mask, making a marked difference. Headaches and nausea are the most commonly reported complaints at concentrations above 50%.

“We did not have patients report headaches or nausea in new study (by the BIDMC group),” she said. This study has been submitted for publication.

Clinicians outside the United States have been quicker to embrace nitrous oxide for prostate procedures.

In a randomized controlled trial, researchers in Australia found no significant improvement in pain scores at 15 minutes from the use of nitrous oxide during transrectal biopsies; however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

Stephen McCombie, MD, a consultant at Perth Urology Clinic, Australia, who has been adapting the nitrous oxide protocol for transrectal biopsies to transperineal procedures, said that the Beth Israel study “adds to the evidence to support adjunct use of mild inhalational anesthetics and analgesics during prostate biopsies to improve the patient experience of the procedure.”

He said that the role for these agents may grow with the global trend away from transrectal prostate biopsies and toward transperineal biopsies, largely driven by increasing rates of sepsis after transrectal biopsies.

“While transperineal biopsies can be more painful then transrectal biopsies when performed under local anesthesia, perhaps due to biopsies being taken through the highly sensate perineum as opposed to above the dentate line, optimization of the technique can significantly reduce the discomfort associated with the procedure, which may be further reduced with these agents,” Dr. McCombie said.

“Studies indicate that transperineal biopsies can be more painful than the traditional transrectal biopsies,” Dr. Rayala said. “We do offer transperineal biopsies at BIDMC, and we are gearing up to repeat the SANO study” for those patients.

Dr. Rayala and Dr. McCombie have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An old dog – nitrous oxide – can learn new tricks, managing pain in men undergoing transrectal biopsies, researchers reported at the annual meeting of the American Urological Association.

“At concentrations of less than 50%, nitrous oxide is classified as a minimal sedative, making it a promising option for many urologic outpatient procedures such as prostate biopsies,” said Heidi Rayala, MD, PhD, assistant professor of surgery at Harvard Medical School, Boston, who helped conduct the study.

Nitrous oxide is best known as a pain medication and anesthetic during dental procedures and childbirth, after trauma, and in end-of-life care.

In the new study, Dr. Rayala and her colleagues at Harvard and Beth Israel-Deaconess Medical Center, Boston, randomly assigned 128 men to self-administered nitrous oxide (SANO) or oxygen as a placebo. Patients in the SANO group had a smaller change in post-biopsy pain score (Visual Analog Scale for pain, 0.43 vs. 1.03; P = .03) and lower odds of experiencing pain during the procedure (odds ratio, 0.45; confidence interval, 0.21-0.97; P = .04).

A comparison of anxiety scores in the two groups failed to find a statistically significant difference between SANO and placebo. However, more men who received nitrous oxide said they tolerated the procedure “better than expected” (61% vs. 41%; P = 0.02), according to the researchers.

Dr. Rayala said that the researchers used the Nitrouseal system (Sedation Systems), in which the patient holds a mask to their face and works with staff to adjust the gas levels to the desired amount. The system is governed to max out at 50% nitrous oxide, ensuring “minimal sedation concentrations, so anesthesia personnel are not required,” she said.

“At levels of less than 50%, patients respond normally to verbal commands and maintain normal airway reflexes,” Dr. Rayala added. “This provides an advantage in that patients do not require the presence of anesthesia personnel.” And because the body eliminates the gas within about 5 minutes, patients do not require an escort home, she said.

This system is also self-scavenging to protect the operating urologist and other personnel from environmental exposure to nitrous oxide.

Dr. Rayala said that three patients (2.3%) found the mask uncomfortable, but in follow-up studies the clinicians have done a better job of preparing patients for the feeling of the mask, making a marked difference. Headaches and nausea are the most commonly reported complaints at concentrations above 50%.

“We did not have patients report headaches or nausea in new study (by the BIDMC group),” she said. This study has been submitted for publication.

Clinicians outside the United States have been quicker to embrace nitrous oxide for prostate procedures.

In a randomized controlled trial, researchers in Australia found no significant improvement in pain scores at 15 minutes from the use of nitrous oxide during transrectal biopsies; however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

Stephen McCombie, MD, a consultant at Perth Urology Clinic, Australia, who has been adapting the nitrous oxide protocol for transrectal biopsies to transperineal procedures, said that the Beth Israel study “adds to the evidence to support adjunct use of mild inhalational anesthetics and analgesics during prostate biopsies to improve the patient experience of the procedure.”

He said that the role for these agents may grow with the global trend away from transrectal prostate biopsies and toward transperineal biopsies, largely driven by increasing rates of sepsis after transrectal biopsies.

“While transperineal biopsies can be more painful then transrectal biopsies when performed under local anesthesia, perhaps due to biopsies being taken through the highly sensate perineum as opposed to above the dentate line, optimization of the technique can significantly reduce the discomfort associated with the procedure, which may be further reduced with these agents,” Dr. McCombie said.

“Studies indicate that transperineal biopsies can be more painful than the traditional transrectal biopsies,” Dr. Rayala said. “We do offer transperineal biopsies at BIDMC, and we are gearing up to repeat the SANO study” for those patients.

Dr. Rayala and Dr. McCombie have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A panel of independent advisers recently almost unanimously recommended to restrict a new indication for olaparib (Lynparza) alongside abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer.

On April 28, members of the Oncologic Drugs Advisory Committee voted 11 to 1, with one abstention, that only patients whose tumors have a BRCA mutation should receive olaparib as part of the combination first-line treatment for metastatic castration-resistant prostate cancer.

Olaparib is already cleared by the Food and Drug Administration for various ovarian, breast, and pancreatic cancer indications as well as later-line use in certain more advanced prostate cancers. AstraZeneca recently applied for an additional, broad indication for the poly (ADP-ribose) polymerase (PARP) inhibitor as an initial therapy that would include patients without BRCA or homologous recombination repair (HRR) mutations.

In reviewing the application, the FDA raised concerns about this broad new indication, highlighting limitations in the key research used to justify the expanded use and highlighting how olaparib may amount to a “toxic placebo,” a phrase agency staff used in their briefing document.

Given these concerns, the FDA reviewers asked the independent ODAC panel to vote on the following question: “As FDA reviews the proposed indication for olaparib in combination with abiraterone for initial treatment of [metastatic castration-resistant prostate cancer], should the indication be restricted to patients whose tumors have a BRCA mutation?”

The ODAC panel voted 11 to 1 in favor of a restricted expansion of olaparib plus abiraterone and prednisone or prednisolone to patients whose tumors have a BRCA mutation. One member – Ravi A. Madan, MD, of the National Cancer Institute – abstained. The FDA staff asked panelists to abstain if they felt the combination treatment should not be approved for any indication.

Overall, the ODAC panel agreed with the FDA staff’s criticism of the research supporting the application: the PROpel study. The trial randomized 796 patients with previously untreated metastatic castration-resistant prostate cancer to olaparib plus abiraterone or abiraterone plus placebo. The median time for radiographic progression-free survival – the study’s primary endpoint – was nearly 25 months in the olaparib group versus 16.6 months in the placebo group.

The combination also demonstrated a 19% reduced risk of death, which was not statistically significant (hazard ratio, 0.81; P = .0544), and a median improvement of 7.4 months in the combination arm (42.1 vs. 34.7 months).

Although the study met its primary endpoint, the results were difficult to interpret given the lack of information about genetic variability in the participants’ tumors. Participants were not prospectively assessed for either BRCA or HRR status. But given the importance of BRCA status as a predictive biomarker for PARP inhibitor efficacy, “this trial design would be considered inappropriate today as the biomarker should have been prospectively evaluated,” the FDA wrote in its briefing document.

In a post hoc analysis performed by the FDA, the agency found that BRCA-positive patients accounted for most of the survival benefit of the combination, though made up only 11% of the PROpel population.

That meant the ODAC members were being asked to evaluate a drug based on “suboptimal data” resulting from a “suboptimal study design,” said Dr. Madan, who is head of the prostate cancer clinical research section in the NCI’s Center for Cancer Research.

Dr. Madan also emphasized concerns the FDA raised about the potential harms for patients whose prostate cancer was not tied to BRCA mutations. In the FDA’s briefing document, the agency said patients treated in the first-line metastatic castration-resistant prostate cancer setting generally have few symptoms at baseline. Adding olaparib among patients lacking the BRCA mutation could expose them to a drug with known side effects but minimal chance to help them.

The PROpel trial also found that patients who received olaparib and abiraterone experienced greater toxicity than those who received abiraterone. These adverse events included venous thromboembolic events, myelosuppression, requirement for blood transfusions, nausea, vomiting, and diarrhea.

Although the FDA is not compelled to follow the recommendations of its advisory committees, it often does.

AstraZeneca expressed some disappointment about the recommendation in a press release. Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said, “while we are pleased with the recognition of the benefit of Lynparza plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated the clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status.”

One ODAC member, Jorge J. Nieva, MD, did support the expanded approval for olaparib, casting the single “no” vote. Dr. Nieva, an oncologist at the University of Southern California, Los Angeles, disagreed with the FDA’s question about limiting use of the olaparib-abiraterone combination to patients with known BRCA mutations, citing the positive result from the PROpel trial.

People are aware that olaparib provides a great deal more benefit in the BRCA-positive group and may give “only minimal benefit if these tests are not positive,” but “these risks and benefits can be addressed at the patient and physician level,” he said.

But Terrence M. Kungel, MBA, who served as ODAC’s patient representative for the meeting, offered a counterpoint to Dr. Nieva’s assessment. Patients now often struggle to assess the options available to them and then pay for these medicines, with financial toxicity affecting many people with cancer.

“Prostate cancer patients need more treatments that are effective, not more choices,” said Mr. Kungel, who voted with the majority.

A version of this article first appeared on Medscape.com.

A panel of independent advisers recently almost unanimously recommended to restrict a new indication for olaparib (Lynparza) alongside abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer.

On April 28, members of the Oncologic Drugs Advisory Committee voted 11 to 1, with one abstention, that only patients whose tumors have a BRCA mutation should receive olaparib as part of the combination first-line treatment for metastatic castration-resistant prostate cancer.

Olaparib is already cleared by the Food and Drug Administration for various ovarian, breast, and pancreatic cancer indications as well as later-line use in certain more advanced prostate cancers. AstraZeneca recently applied for an additional, broad indication for the poly (ADP-ribose) polymerase (PARP) inhibitor as an initial therapy that would include patients without BRCA or homologous recombination repair (HRR) mutations.

In reviewing the application, the FDA raised concerns about this broad new indication, highlighting limitations in the key research used to justify the expanded use and highlighting how olaparib may amount to a “toxic placebo,” a phrase agency staff used in their briefing document.

Given these concerns, the FDA reviewers asked the independent ODAC panel to vote on the following question: “As FDA reviews the proposed indication for olaparib in combination with abiraterone for initial treatment of [metastatic castration-resistant prostate cancer], should the indication be restricted to patients whose tumors have a BRCA mutation?”

The ODAC panel voted 11 to 1 in favor of a restricted expansion of olaparib plus abiraterone and prednisone or prednisolone to patients whose tumors have a BRCA mutation. One member – Ravi A. Madan, MD, of the National Cancer Institute – abstained. The FDA staff asked panelists to abstain if they felt the combination treatment should not be approved for any indication.

Overall, the ODAC panel agreed with the FDA staff’s criticism of the research supporting the application: the PROpel study. The trial randomized 796 patients with previously untreated metastatic castration-resistant prostate cancer to olaparib plus abiraterone or abiraterone plus placebo. The median time for radiographic progression-free survival – the study’s primary endpoint – was nearly 25 months in the olaparib group versus 16.6 months in the placebo group.

The combination also demonstrated a 19% reduced risk of death, which was not statistically significant (hazard ratio, 0.81; P = .0544), and a median improvement of 7.4 months in the combination arm (42.1 vs. 34.7 months).

Although the study met its primary endpoint, the results were difficult to interpret given the lack of information about genetic variability in the participants’ tumors. Participants were not prospectively assessed for either BRCA or HRR status. But given the importance of BRCA status as a predictive biomarker for PARP inhibitor efficacy, “this trial design would be considered inappropriate today as the biomarker should have been prospectively evaluated,” the FDA wrote in its briefing document.

In a post hoc analysis performed by the FDA, the agency found that BRCA-positive patients accounted for most of the survival benefit of the combination, though made up only 11% of the PROpel population.

That meant the ODAC members were being asked to evaluate a drug based on “suboptimal data” resulting from a “suboptimal study design,” said Dr. Madan, who is head of the prostate cancer clinical research section in the NCI’s Center for Cancer Research.

Dr. Madan also emphasized concerns the FDA raised about the potential harms for patients whose prostate cancer was not tied to BRCA mutations. In the FDA’s briefing document, the agency said patients treated in the first-line metastatic castration-resistant prostate cancer setting generally have few symptoms at baseline. Adding olaparib among patients lacking the BRCA mutation could expose them to a drug with known side effects but minimal chance to help them.

The PROpel trial also found that patients who received olaparib and abiraterone experienced greater toxicity than those who received abiraterone. These adverse events included venous thromboembolic events, myelosuppression, requirement for blood transfusions, nausea, vomiting, and diarrhea.

Although the FDA is not compelled to follow the recommendations of its advisory committees, it often does.

AstraZeneca expressed some disappointment about the recommendation in a press release. Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said, “while we are pleased with the recognition of the benefit of Lynparza plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated the clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status.”

One ODAC member, Jorge J. Nieva, MD, did support the expanded approval for olaparib, casting the single “no” vote. Dr. Nieva, an oncologist at the University of Southern California, Los Angeles, disagreed with the FDA’s question about limiting use of the olaparib-abiraterone combination to patients with known BRCA mutations, citing the positive result from the PROpel trial.

People are aware that olaparib provides a great deal more benefit in the BRCA-positive group and may give “only minimal benefit if these tests are not positive,” but “these risks and benefits can be addressed at the patient and physician level,” he said.

But Terrence M. Kungel, MBA, who served as ODAC’s patient representative for the meeting, offered a counterpoint to Dr. Nieva’s assessment. Patients now often struggle to assess the options available to them and then pay for these medicines, with financial toxicity affecting many people with cancer.

“Prostate cancer patients need more treatments that are effective, not more choices,” said Mr. Kungel, who voted with the majority.

A version of this article first appeared on Medscape.com.

A panel of independent advisers recently almost unanimously recommended to restrict a new indication for olaparib (Lynparza) alongside abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer.

On April 28, members of the Oncologic Drugs Advisory Committee voted 11 to 1, with one abstention, that only patients whose tumors have a BRCA mutation should receive olaparib as part of the combination first-line treatment for metastatic castration-resistant prostate cancer.

Olaparib is already cleared by the Food and Drug Administration for various ovarian, breast, and pancreatic cancer indications as well as later-line use in certain more advanced prostate cancers. AstraZeneca recently applied for an additional, broad indication for the poly (ADP-ribose) polymerase (PARP) inhibitor as an initial therapy that would include patients without BRCA or homologous recombination repair (HRR) mutations.

In reviewing the application, the FDA raised concerns about this broad new indication, highlighting limitations in the key research used to justify the expanded use and highlighting how olaparib may amount to a “toxic placebo,” a phrase agency staff used in their briefing document.

Given these concerns, the FDA reviewers asked the independent ODAC panel to vote on the following question: “As FDA reviews the proposed indication for olaparib in combination with abiraterone for initial treatment of [metastatic castration-resistant prostate cancer], should the indication be restricted to patients whose tumors have a BRCA mutation?”

The ODAC panel voted 11 to 1 in favor of a restricted expansion of olaparib plus abiraterone and prednisone or prednisolone to patients whose tumors have a BRCA mutation. One member – Ravi A. Madan, MD, of the National Cancer Institute – abstained. The FDA staff asked panelists to abstain if they felt the combination treatment should not be approved for any indication.

Overall, the ODAC panel agreed with the FDA staff’s criticism of the research supporting the application: the PROpel study. The trial randomized 796 patients with previously untreated metastatic castration-resistant prostate cancer to olaparib plus abiraterone or abiraterone plus placebo. The median time for radiographic progression-free survival – the study’s primary endpoint – was nearly 25 months in the olaparib group versus 16.6 months in the placebo group.

The combination also demonstrated a 19% reduced risk of death, which was not statistically significant (hazard ratio, 0.81; P = .0544), and a median improvement of 7.4 months in the combination arm (42.1 vs. 34.7 months).

Although the study met its primary endpoint, the results were difficult to interpret given the lack of information about genetic variability in the participants’ tumors. Participants were not prospectively assessed for either BRCA or HRR status. But given the importance of BRCA status as a predictive biomarker for PARP inhibitor efficacy, “this trial design would be considered inappropriate today as the biomarker should have been prospectively evaluated,” the FDA wrote in its briefing document.

In a post hoc analysis performed by the FDA, the agency found that BRCA-positive patients accounted for most of the survival benefit of the combination, though made up only 11% of the PROpel population.

That meant the ODAC members were being asked to evaluate a drug based on “suboptimal data” resulting from a “suboptimal study design,” said Dr. Madan, who is head of the prostate cancer clinical research section in the NCI’s Center for Cancer Research.

Dr. Madan also emphasized concerns the FDA raised about the potential harms for patients whose prostate cancer was not tied to BRCA mutations. In the FDA’s briefing document, the agency said patients treated in the first-line metastatic castration-resistant prostate cancer setting generally have few symptoms at baseline. Adding olaparib among patients lacking the BRCA mutation could expose them to a drug with known side effects but minimal chance to help them.

The PROpel trial also found that patients who received olaparib and abiraterone experienced greater toxicity than those who received abiraterone. These adverse events included venous thromboembolic events, myelosuppression, requirement for blood transfusions, nausea, vomiting, and diarrhea.

Although the FDA is not compelled to follow the recommendations of its advisory committees, it often does.

AstraZeneca expressed some disappointment about the recommendation in a press release. Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said, “while we are pleased with the recognition of the benefit of Lynparza plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated the clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status.”

One ODAC member, Jorge J. Nieva, MD, did support the expanded approval for olaparib, casting the single “no” vote. Dr. Nieva, an oncologist at the University of Southern California, Los Angeles, disagreed with the FDA’s question about limiting use of the olaparib-abiraterone combination to patients with known BRCA mutations, citing the positive result from the PROpel trial.

People are aware that olaparib provides a great deal more benefit in the BRCA-positive group and may give “only minimal benefit if these tests are not positive,” but “these risks and benefits can be addressed at the patient and physician level,” he said.

But Terrence M. Kungel, MBA, who served as ODAC’s patient representative for the meeting, offered a counterpoint to Dr. Nieva’s assessment. Patients now often struggle to assess the options available to them and then pay for these medicines, with financial toxicity affecting many people with cancer.

“Prostate cancer patients need more treatments that are effective, not more choices,” said Mr. Kungel, who voted with the majority.

A version of this article first appeared on Medscape.com.

There is one situation, while not common, that is often among the most difficult for me: the person who must be told at diagnosis that they are already dying. I am still reminded of a patient I saw early in my career.

A woman in her 40s was admitted to the hospital complaining of severe shortness of breath. In retrospect, she had been sick for months. She had not sought help because she was young and thought it would pass – the results of a “bad bug” that she just couldn’t shake.

But in the past few weeks, the persistence of symptoms became associated with weight loss, profound fatigue, loss of appetite, and nausea.

By the time she was hospitalized she was emaciated, though she appeared pregnant – a sign of the fluid that had built up in her abdomen. Imaging showed that her abdomen was filled with disease (carcinomatosis) and her liver and lungs were nearly replaced with metastatic disease.

A biopsy revealed an aggressive cancer that had no identifying histologic marker: carcinoma, not otherwise specified, or cancer of unknown primary.

I still remember seeing her. She had a deer-in-headlights stare that held me as I approached. I introduced myself and sat down so we were eye to eye.

“Tell me what you know,” I said.

“I know I have cancer and they don’t know where it started. I know surgery is not an option and that’s why they’ve asked you to come. Whatever. I’m ready. I want to fight this because I know I can beat it,” she said.

I remember that she looked very sick; her thin face and arms contrasted with her large, distended abdomen. Her breathing was labored, her skin almost gray. For a moment I didn’t know what to say.

As doctors, we like to believe that our decisions are guided by data: the randomized trials and meta-analyses that set standards of care; phase 2 trials that establish evidence (or lack thereof) of activity; case-control studies that suggest the impacts of treatment; and at the very least, case studies that document that “N of 1” experience. We have expert panels and pathways that lay out what treatments we should be using to help ensure access to quality care in every clinic on every corner of every cancer center in the United States.

These data and pathways tell us objectively what we can expect from therapy, who is at most risk for toxicities, and profiles of patients for whom treatment is not likely to be of benefit. In an ideal world, this objectivity would help us help people decide on an approach. But life is not objective, and sometimes individualizing care is as important as data.

In this scenario, I knew only one thing: She was dying. She had an overwhelming tumor burden. But I still asked myself a question that many in, and outside of, oncology ask themselves: Could she be saved?

This question was made even more difficult because she was young. She had her whole life ahead of her. It seemed incongruous that she would be here now, facing the gravity of her situation.

Looking at her, I saw the person, not a data point in a trial or a statistic in a textbook. She was terrified. And she was not ready to die.

I sat down and reviewed what I knew about her cancer and what I did not know. I went through potential treatments we could try and the toxicities associated with each. I made clear that these treatments, based on how sick she was, could kill her.

“Whatever we do,” I said, “you do not have disease that I can cure.”

She cried then, realizing what a horrible situation she was in and that she would no longer go back to her normal life. Indeed, she seemed to grasp that she was probably facing the end of her life and that it could be short.

“My concern is,” I continued, “that treatment could do the exact opposite of what I hope it would do. It could kill you sooner than this cancer will.”

Instead of making a treatment plan, I decided that it would be best to come back another day, so I said my goodbyes and left. Still, I could not stop thinking about her and what I should suggest as her next steps. My heart wanted to try treatment, give her a chance, even if it killed her. But my brain told me that treatment is not likely to work and may make her life even shorter.

I asked colleagues what they would suggest. Some recommended hospice care, others recommended treatment. Clearly, there was no one way to proceed.

One might wonder: Why is it so hard to do the right thing?

Ask any clinician and I think you will hear the same answer: Because we do not have the luxury of certainty.

Am I certain that this person will not benefit from intubation? Am I certain that she has only weeks to live? Am I sure that there are no treatments that will work?

The answer to these questions is no – I am not certain. It is that uncertainty that always makes me pause because it reminds me of my own humanity.

I stopped by the next day to see her surrounded by family. After some pleasantries I took the opportunity to reiterate much of our conversation from the other day. After some questions, I looked at her and asked if she wanted to talk more about her options. I was prepared to suggest treatment, anticipating that she would want it. Instead, she told me she didn’t want to proceed.

“I feel like I’m dying, and if what you have to give me isn’t going to cure me, then I’d prefer not to suffer while it happens. You said it’s up to me. I don’t want it.”

First, do no harm. It’s one of the tenets of medicine – to provide care that will benefit the people who have trusted us with their lives, whether that be longevity, relief of symptoms, or helping them achieve their last wishes. Throughout one’s life, goals might change but that edict remains the same.

But that can be difficult, especially in oncology and especially when one is not prepared for their own end of life. It can be hard for doctors to discuss the end of life; it’s easier to focus on the next treatment, instilling hope that there’s more that can be done. And there are people with end-stage cancer who insist on continuing treatment in the same circumstances, preferring to “die fighting” than to “give up.” Involving supportive and palliative care specialists early has helped in both situations, which is certainly a good thing.

We talked a while more and then arranged for our palliative care team to see her. I wish I could say I was at peace with her decision, but I wasn’t. The truth is, whatever she decided would probably have the same impact: I wouldn’t be able to stop thinking about it.

Dr. Dizon is professor of medicine, department of medicine, at Brown University and director of medical oncology at Rhode Island Hospital, both in Providence, R.I. He disclosed conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol Myers Squibb, and Kazia.

A version of this article first appeared on Medscape.com.

There is one situation, while not common, that is often among the most difficult for me: the person who must be told at diagnosis that they are already dying. I am still reminded of a patient I saw early in my career.

A woman in her 40s was admitted to the hospital complaining of severe shortness of breath. In retrospect, she had been sick for months. She had not sought help because she was young and thought it would pass – the results of a “bad bug” that she just couldn’t shake.

But in the past few weeks, the persistence of symptoms became associated with weight loss, profound fatigue, loss of appetite, and nausea.

By the time she was hospitalized she was emaciated, though she appeared pregnant – a sign of the fluid that had built up in her abdomen. Imaging showed that her abdomen was filled with disease (carcinomatosis) and her liver and lungs were nearly replaced with metastatic disease.

A biopsy revealed an aggressive cancer that had no identifying histologic marker: carcinoma, not otherwise specified, or cancer of unknown primary.

I still remember seeing her. She had a deer-in-headlights stare that held me as I approached. I introduced myself and sat down so we were eye to eye.

“Tell me what you know,” I said.

“I know I have cancer and they don’t know where it started. I know surgery is not an option and that’s why they’ve asked you to come. Whatever. I’m ready. I want to fight this because I know I can beat it,” she said.

I remember that she looked very sick; her thin face and arms contrasted with her large, distended abdomen. Her breathing was labored, her skin almost gray. For a moment I didn’t know what to say.

As doctors, we like to believe that our decisions are guided by data: the randomized trials and meta-analyses that set standards of care; phase 2 trials that establish evidence (or lack thereof) of activity; case-control studies that suggest the impacts of treatment; and at the very least, case studies that document that “N of 1” experience. We have expert panels and pathways that lay out what treatments we should be using to help ensure access to quality care in every clinic on every corner of every cancer center in the United States.

These data and pathways tell us objectively what we can expect from therapy, who is at most risk for toxicities, and profiles of patients for whom treatment is not likely to be of benefit. In an ideal world, this objectivity would help us help people decide on an approach. But life is not objective, and sometimes individualizing care is as important as data.

In this scenario, I knew only one thing: She was dying. She had an overwhelming tumor burden. But I still asked myself a question that many in, and outside of, oncology ask themselves: Could she be saved?

This question was made even more difficult because she was young. She had her whole life ahead of her. It seemed incongruous that she would be here now, facing the gravity of her situation.

Looking at her, I saw the person, not a data point in a trial or a statistic in a textbook. She was terrified. And she was not ready to die.

I sat down and reviewed what I knew about her cancer and what I did not know. I went through potential treatments we could try and the toxicities associated with each. I made clear that these treatments, based on how sick she was, could kill her.

“Whatever we do,” I said, “you do not have disease that I can cure.”

She cried then, realizing what a horrible situation she was in and that she would no longer go back to her normal life. Indeed, she seemed to grasp that she was probably facing the end of her life and that it could be short.

“My concern is,” I continued, “that treatment could do the exact opposite of what I hope it would do. It could kill you sooner than this cancer will.”

Instead of making a treatment plan, I decided that it would be best to come back another day, so I said my goodbyes and left. Still, I could not stop thinking about her and what I should suggest as her next steps. My heart wanted to try treatment, give her a chance, even if it killed her. But my brain told me that treatment is not likely to work and may make her life even shorter.

I asked colleagues what they would suggest. Some recommended hospice care, others recommended treatment. Clearly, there was no one way to proceed.

One might wonder: Why is it so hard to do the right thing?

Ask any clinician and I think you will hear the same answer: Because we do not have the luxury of certainty.

Am I certain that this person will not benefit from intubation? Am I certain that she has only weeks to live? Am I sure that there are no treatments that will work?

The answer to these questions is no – I am not certain. It is that uncertainty that always makes me pause because it reminds me of my own humanity.

I stopped by the next day to see her surrounded by family. After some pleasantries I took the opportunity to reiterate much of our conversation from the other day. After some questions, I looked at her and asked if she wanted to talk more about her options. I was prepared to suggest treatment, anticipating that she would want it. Instead, she told me she didn’t want to proceed.

“I feel like I’m dying, and if what you have to give me isn’t going to cure me, then I’d prefer not to suffer while it happens. You said it’s up to me. I don’t want it.”

First, do no harm. It’s one of the tenets of medicine – to provide care that will benefit the people who have trusted us with their lives, whether that be longevity, relief of symptoms, or helping them achieve their last wishes. Throughout one’s life, goals might change but that edict remains the same.

But that can be difficult, especially in oncology and especially when one is not prepared for their own end of life. It can be hard for doctors to discuss the end of life; it’s easier to focus on the next treatment, instilling hope that there’s more that can be done. And there are people with end-stage cancer who insist on continuing treatment in the same circumstances, preferring to “die fighting” than to “give up.” Involving supportive and palliative care specialists early has helped in both situations, which is certainly a good thing.

We talked a while more and then arranged for our palliative care team to see her. I wish I could say I was at peace with her decision, but I wasn’t. The truth is, whatever she decided would probably have the same impact: I wouldn’t be able to stop thinking about it.

Dr. Dizon is professor of medicine, department of medicine, at Brown University and director of medical oncology at Rhode Island Hospital, both in Providence, R.I. He disclosed conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol Myers Squibb, and Kazia.

A version of this article first appeared on Medscape.com.

There is one situation, while not common, that is often among the most difficult for me: the person who must be told at diagnosis that they are already dying. I am still reminded of a patient I saw early in my career.

A woman in her 40s was admitted to the hospital complaining of severe shortness of breath. In retrospect, she had been sick for months. She had not sought help because she was young and thought it would pass – the results of a “bad bug” that she just couldn’t shake.

But in the past few weeks, the persistence of symptoms became associated with weight loss, profound fatigue, loss of appetite, and nausea.

By the time she was hospitalized she was emaciated, though she appeared pregnant – a sign of the fluid that had built up in her abdomen. Imaging showed that her abdomen was filled with disease (carcinomatosis) and her liver and lungs were nearly replaced with metastatic disease.

A biopsy revealed an aggressive cancer that had no identifying histologic marker: carcinoma, not otherwise specified, or cancer of unknown primary.

I still remember seeing her. She had a deer-in-headlights stare that held me as I approached. I introduced myself and sat down so we were eye to eye.

“Tell me what you know,” I said.

“I know I have cancer and they don’t know where it started. I know surgery is not an option and that’s why they’ve asked you to come. Whatever. I’m ready. I want to fight this because I know I can beat it,” she said.

I remember that she looked very sick; her thin face and arms contrasted with her large, distended abdomen. Her breathing was labored, her skin almost gray. For a moment I didn’t know what to say.

As doctors, we like to believe that our decisions are guided by data: the randomized trials and meta-analyses that set standards of care; phase 2 trials that establish evidence (or lack thereof) of activity; case-control studies that suggest the impacts of treatment; and at the very least, case studies that document that “N of 1” experience. We have expert panels and pathways that lay out what treatments we should be using to help ensure access to quality care in every clinic on every corner of every cancer center in the United States.

These data and pathways tell us objectively what we can expect from therapy, who is at most risk for toxicities, and profiles of patients for whom treatment is not likely to be of benefit. In an ideal world, this objectivity would help us help people decide on an approach. But life is not objective, and sometimes individualizing care is as important as data.

In this scenario, I knew only one thing: She was dying. She had an overwhelming tumor burden. But I still asked myself a question that many in, and outside of, oncology ask themselves: Could she be saved?

This question was made even more difficult because she was young. She had her whole life ahead of her. It seemed incongruous that she would be here now, facing the gravity of her situation.

Looking at her, I saw the person, not a data point in a trial or a statistic in a textbook. She was terrified. And she was not ready to die.

I sat down and reviewed what I knew about her cancer and what I did not know. I went through potential treatments we could try and the toxicities associated with each. I made clear that these treatments, based on how sick she was, could kill her.

“Whatever we do,” I said, “you do not have disease that I can cure.”

She cried then, realizing what a horrible situation she was in and that she would no longer go back to her normal life. Indeed, she seemed to grasp that she was probably facing the end of her life and that it could be short.

“My concern is,” I continued, “that treatment could do the exact opposite of what I hope it would do. It could kill you sooner than this cancer will.”

Instead of making a treatment plan, I decided that it would be best to come back another day, so I said my goodbyes and left. Still, I could not stop thinking about her and what I should suggest as her next steps. My heart wanted to try treatment, give her a chance, even if it killed her. But my brain told me that treatment is not likely to work and may make her life even shorter.

I asked colleagues what they would suggest. Some recommended hospice care, others recommended treatment. Clearly, there was no one way to proceed.

One might wonder: Why is it so hard to do the right thing?

Ask any clinician and I think you will hear the same answer: Because we do not have the luxury of certainty.

Am I certain that this person will not benefit from intubation? Am I certain that she has only weeks to live? Am I sure that there are no treatments that will work?

The answer to these questions is no – I am not certain. It is that uncertainty that always makes me pause because it reminds me of my own humanity.

I stopped by the next day to see her surrounded by family. After some pleasantries I took the opportunity to reiterate much of our conversation from the other day. After some questions, I looked at her and asked if she wanted to talk more about her options. I was prepared to suggest treatment, anticipating that she would want it. Instead, she told me she didn’t want to proceed.

“I feel like I’m dying, and if what you have to give me isn’t going to cure me, then I’d prefer not to suffer while it happens. You said it’s up to me. I don’t want it.”

First, do no harm. It’s one of the tenets of medicine – to provide care that will benefit the people who have trusted us with their lives, whether that be longevity, relief of symptoms, or helping them achieve their last wishes. Throughout one’s life, goals might change but that edict remains the same.

But that can be difficult, especially in oncology and especially when one is not prepared for their own end of life. It can be hard for doctors to discuss the end of life; it’s easier to focus on the next treatment, instilling hope that there’s more that can be done. And there are people with end-stage cancer who insist on continuing treatment in the same circumstances, preferring to “die fighting” than to “give up.” Involving supportive and palliative care specialists early has helped in both situations, which is certainly a good thing.

We talked a while more and then arranged for our palliative care team to see her. I wish I could say I was at peace with her decision, but I wasn’t. The truth is, whatever she decided would probably have the same impact: I wouldn’t be able to stop thinking about it.

Dr. Dizon is professor of medicine, department of medicine, at Brown University and director of medical oncology at Rhode Island Hospital, both in Providence, R.I. He disclosed conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol Myers Squibb, and Kazia.

A version of this article first appeared on Medscape.com.

The first guideline for definitive local therapy options in the treatment of oligometastatic non–small cell lung cancer (NSCLC) has now been released.

The result of a joint effort by the American Society for Radiation Oncology and European Society for Radiotherapy and Oncology, the guidelines emphasizes the need for a multidisciplinary team approach to guide treatment decisions for oligometastatic disease.

Historically, treatment for oligometastatic NSCLC has involved systemic therapy including chemotherapy or immunotherapy, and local therapy was given only for palliation and symptom relief. But increasing evidence has demonstrated that definitive local therapy may have an additional role in controlling tumor growth and improving survival outcomes, and an increasing number of radiation oncologists and multidisciplinary teams are now using local therapy beyond palliative care for these patients, the authors noted.

“Oligometastatic NSCLC is a phase in lung cancer development that may offer us new opportunities to improve patient outcomes, because it typically is more treatable than widely metastatic cancer,” said Puneeth Iyengar, MD, PhD, cochair of the guideline task force and an associate professor of radiation oncology at UT Southwestern Medical Center, Dallas.

“The research on local therapy for oligometastatic cancer is still at a relatively early stage, but we already see indicators of potential benefits for patients. Adding local therapy to systemic therapy may lead to more durable cancer control, potentially improving progression-free survival, overall survival and quality of life,” he said in a statement.

The new guideline is published in Practical Radiation Oncology.

The purpose of this joint guideline was to provide recommendations on local therapy use for oligometastatic NSCLC, along with a summary of the evidence justifying its incorporation into standard treatment paradigms.
 

Key recommendations

Owing to the lack of significant randomized phase 3 trials, the guideline task force strongly recommended a patient-centered, multidisciplinary approach for all decision-making regarding potential treatment. In addition, algorithms were also created for the optimal clinical scenarios for local therapy and the different types of local therapy that are available for these patients.

Key recommendations include:

• The integration of definitive local therapy is recommended only for patients who have five or fewer distant extracranial metastases, and only when technically feasible and clinically safe for all disease sites. Definitive local therapy is also conditionally recommended for carefully selected patients with synchronous oligometastatic, metachronous oligorecurrent, induced oligopersistent, or induced oligoprogressive conditions for extracranial NSCLC.
• Radiation and surgery are the only recommended modalities for definitive local treatment of oligometastatic NSCLC. Radiation is favored when multiple organ systems are being treated or when the clinical priority is to minimize breaks from systemic therapy, whereas surgery is favored when large tissue sampling is needed for molecular testing to guide systemic therapy.
• For sequencing and timing, there is an emphasis on upfront, definitive local treatment for symptomatic metastases. For asymptomatic patients with synchronous disease, at least 3 months of standard-of-care systemic therapy is recommended before starting definitive local therapy.
• For optimal staging, radiation dosing, treatment planning, and delivery techniques, there is a preference for hypofractionated radiation therapy or stereotactic body radiation therapy when appropriate. The task force also emphasizes the importance of appropriate imaging and comments that it “cannot be overstated” to diagnose oligometastatic disease; they recommend that care teams consult guidelines from groups such as the National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer.
• Patients who develop disease progression at a limited number of sites, so-called oligoprogression at previously treated sites, and/or de novo recurrences at new sites may benefit from repeat local definitive therapy performed with the aim of prolonging progression-free survival or delaying a switch in systemic therapies.

Matthias Guckenberger, MD, cochair of the guideline task force and a professor and chairman of radiation oncology at the University Hospital Zürich, cautioned that “despite the widespread enthusiasm in the field of oligometastatic disease, the quality of evidence supporting the integration of definitive local therapy into a multimodality treatment strategy is still lower as compared to indications such as locally advanced NSCLC.”

“To compensate for this lack of highest-quality evidence, recommendations of this guideline were established by a broad consensus involving experts from ASTRO and ESTRO, colleagues from the fields of thoracic surgery and medical oncology and a patient representative,” Dr. Guckenberger said in a statement.

The guideline task force also emphasized the need for equitable use of these techniques, noting that “a significant effort must be taken to ensure that the decisions regarding the use of local therapies for oligometastatic NSCLC be applied equally across all patients to avoid any health disparities.”

This work was funded by ASTRO. Dr. Iyengar reported no disclosures. Dr. Guckenberger reports relationships with the European Thoracic Oncology Platform, Varian, ViewRay, and ESTRO. Several of the coauthors disclosed relationships with industry.

A version of this article first appeared on Medscape.com.

The first guideline for definitive local therapy options in the treatment of oligometastatic non–small cell lung cancer (NSCLC) has now been released.

The result of a joint effort by the American Society for Radiation Oncology and European Society for Radiotherapy and Oncology, the guidelines emphasizes the need for a multidisciplinary team approach to guide treatment decisions for oligometastatic disease.

Historically, treatment for oligometastatic NSCLC has involved systemic therapy including chemotherapy or immunotherapy, and local therapy was given only for palliation and symptom relief. But increasing evidence has demonstrated that definitive local therapy may have an additional role in controlling tumor growth and improving survival outcomes, and an increasing number of radiation oncologists and multidisciplinary teams are now using local therapy beyond palliative care for these patients, the authors noted.

“Oligometastatic NSCLC is a phase in lung cancer development that may offer us new opportunities to improve patient outcomes, because it typically is more treatable than widely metastatic cancer,” said Puneeth Iyengar, MD, PhD, cochair of the guideline task force and an associate professor of radiation oncology at UT Southwestern Medical Center, Dallas.

“The research on local therapy for oligometastatic cancer is still at a relatively early stage, but we already see indicators of potential benefits for patients. Adding local therapy to systemic therapy may lead to more durable cancer control, potentially improving progression-free survival, overall survival and quality of life,” he said in a statement.

The new guideline is published in Practical Radiation Oncology.

The purpose of this joint guideline was to provide recommendations on local therapy use for oligometastatic NSCLC, along with a summary of the evidence justifying its incorporation into standard treatment paradigms.
 

Key recommendations

Owing to the lack of significant randomized phase 3 trials, the guideline task force strongly recommended a patient-centered, multidisciplinary approach for all decision-making regarding potential treatment. In addition, algorithms were also created for the optimal clinical scenarios for local therapy and the different types of local therapy that are available for these patients.

Key recommendations include:

• The integration of definitive local therapy is recommended only for patients who have five or fewer distant extracranial metastases, and only when technically feasible and clinically safe for all disease sites. Definitive local therapy is also conditionally recommended for carefully selected patients with synchronous oligometastatic, metachronous oligorecurrent, induced oligopersistent, or induced oligoprogressive conditions for extracranial NSCLC.
• Radiation and surgery are the only recommended modalities for definitive local treatment of oligometastatic NSCLC. Radiation is favored when multiple organ systems are being treated or when the clinical priority is to minimize breaks from systemic therapy, whereas surgery is favored when large tissue sampling is needed for molecular testing to guide systemic therapy.
• For sequencing and timing, there is an emphasis on upfront, definitive local treatment for symptomatic metastases. For asymptomatic patients with synchronous disease, at least 3 months of standard-of-care systemic therapy is recommended before starting definitive local therapy.
• For optimal staging, radiation dosing, treatment planning, and delivery techniques, there is a preference for hypofractionated radiation therapy or stereotactic body radiation therapy when appropriate. The task force also emphasizes the importance of appropriate imaging and comments that it “cannot be overstated” to diagnose oligometastatic disease; they recommend that care teams consult guidelines from groups such as the National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer.
• Patients who develop disease progression at a limited number of sites, so-called oligoprogression at previously treated sites, and/or de novo recurrences at new sites may benefit from repeat local definitive therapy performed with the aim of prolonging progression-free survival or delaying a switch in systemic therapies.

Matthias Guckenberger, MD, cochair of the guideline task force and a professor and chairman of radiation oncology at the University Hospital Zürich, cautioned that “despite the widespread enthusiasm in the field of oligometastatic disease, the quality of evidence supporting the integration of definitive local therapy into a multimodality treatment strategy is still lower as compared to indications such as locally advanced NSCLC.”

“To compensate for this lack of highest-quality evidence, recommendations of this guideline were established by a broad consensus involving experts from ASTRO and ESTRO, colleagues from the fields of thoracic surgery and medical oncology and a patient representative,” Dr. Guckenberger said in a statement.

The guideline task force also emphasized the need for equitable use of these techniques, noting that “a significant effort must be taken to ensure that the decisions regarding the use of local therapies for oligometastatic NSCLC be applied equally across all patients to avoid any health disparities.”

This work was funded by ASTRO. Dr. Iyengar reported no disclosures. Dr. Guckenberger reports relationships with the European Thoracic Oncology Platform, Varian, ViewRay, and ESTRO. Several of the coauthors disclosed relationships with industry.

A version of this article first appeared on Medscape.com.

The first guideline for definitive local therapy options in the treatment of oligometastatic non–small cell lung cancer (NSCLC) has now been released.

The result of a joint effort by the American Society for Radiation Oncology and European Society for Radiotherapy and Oncology, the guidelines emphasizes the need for a multidisciplinary team approach to guide treatment decisions for oligometastatic disease.

Historically, treatment for oligometastatic NSCLC has involved systemic therapy including chemotherapy or immunotherapy, and local therapy was given only for palliation and symptom relief. But increasing evidence has demonstrated that definitive local therapy may have an additional role in controlling tumor growth and improving survival outcomes, and an increasing number of radiation oncologists and multidisciplinary teams are now using local therapy beyond palliative care for these patients, the authors noted.

“Oligometastatic NSCLC is a phase in lung cancer development that may offer us new opportunities to improve patient outcomes, because it typically is more treatable than widely metastatic cancer,” said Puneeth Iyengar, MD, PhD, cochair of the guideline task force and an associate professor of radiation oncology at UT Southwestern Medical Center, Dallas.

“The research on local therapy for oligometastatic cancer is still at a relatively early stage, but we already see indicators of potential benefits for patients. Adding local therapy to systemic therapy may lead to more durable cancer control, potentially improving progression-free survival, overall survival and quality of life,” he said in a statement.

The new guideline is published in Practical Radiation Oncology.

The purpose of this joint guideline was to provide recommendations on local therapy use for oligometastatic NSCLC, along with a summary of the evidence justifying its incorporation into standard treatment paradigms.
 

Key recommendations

Owing to the lack of significant randomized phase 3 trials, the guideline task force strongly recommended a patient-centered, multidisciplinary approach for all decision-making regarding potential treatment. In addition, algorithms were also created for the optimal clinical scenarios for local therapy and the different types of local therapy that are available for these patients.

Key recommendations include:

• The integration of definitive local therapy is recommended only for patients who have five or fewer distant extracranial metastases, and only when technically feasible and clinically safe for all disease sites. Definitive local therapy is also conditionally recommended for carefully selected patients with synchronous oligometastatic, metachronous oligorecurrent, induced oligopersistent, or induced oligoprogressive conditions for extracranial NSCLC.
• Radiation and surgery are the only recommended modalities for definitive local treatment of oligometastatic NSCLC. Radiation is favored when multiple organ systems are being treated or when the clinical priority is to minimize breaks from systemic therapy, whereas surgery is favored when large tissue sampling is needed for molecular testing to guide systemic therapy.
• For sequencing and timing, there is an emphasis on upfront, definitive local treatment for symptomatic metastases. For asymptomatic patients with synchronous disease, at least 3 months of standard-of-care systemic therapy is recommended before starting definitive local therapy.
• For optimal staging, radiation dosing, treatment planning, and delivery techniques, there is a preference for hypofractionated radiation therapy or stereotactic body radiation therapy when appropriate. The task force also emphasizes the importance of appropriate imaging and comments that it “cannot be overstated” to diagnose oligometastatic disease; they recommend that care teams consult guidelines from groups such as the National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer.
• Patients who develop disease progression at a limited number of sites, so-called oligoprogression at previously treated sites, and/or de novo recurrences at new sites may benefit from repeat local definitive therapy performed with the aim of prolonging progression-free survival or delaying a switch in systemic therapies.

Matthias Guckenberger, MD, cochair of the guideline task force and a professor and chairman of radiation oncology at the University Hospital Zürich, cautioned that “despite the widespread enthusiasm in the field of oligometastatic disease, the quality of evidence supporting the integration of definitive local therapy into a multimodality treatment strategy is still lower as compared to indications such as locally advanced NSCLC.”

“To compensate for this lack of highest-quality evidence, recommendations of this guideline were established by a broad consensus involving experts from ASTRO and ESTRO, colleagues from the fields of thoracic surgery and medical oncology and a patient representative,” Dr. Guckenberger said in a statement.

The guideline task force also emphasized the need for equitable use of these techniques, noting that “a significant effort must be taken to ensure that the decisions regarding the use of local therapies for oligometastatic NSCLC be applied equally across all patients to avoid any health disparities.”

This work was funded by ASTRO. Dr. Iyengar reported no disclosures. Dr. Guckenberger reports relationships with the European Thoracic Oncology Platform, Varian, ViewRay, and ESTRO. Several of the coauthors disclosed relationships with industry.

A version of this article first appeared on Medscape.com.

Cisplatin is one of the most commonly used chemotherapeutic agents for treating a variety of cancers, such as lung, bladder, and ovarian cancers. But the therapy comes with a drawback – ototoxicity.

“More than half of adult and pediatric patients with cancer treated with cisplatin developed hearing impairment with major impact on patients’ health-related quality of life,” researchers noted in a clinical review published in JCO Oncology Practice.

It is estimated that 36% of adult patients and 40%-60% of pediatric patients experience cisplatin-induced ototoxicity. It can present as tinnitus (ringing in the ears), loss of hearing in the high-frequency range (4000 – 8000 Hz), or, at late stages, a decrease in the ability to hear lower frequencies.

The incidence of cisplatin-induced ototoxicity is estimated to be 36% of adult patients and 40% to 60% of pediatric patients. Ototoxicity can present as tinnitus, loss of hearing in the high-frequency range (4,000-8,000 Hz), or, at late stages, a decrease in the ability to hear lower frequencies.

The risk of developing cisplatin-induced ototoxicity depends on various factors, including the cumulative dose of cisplatin, the duration of treatment, and individual patient factors, such as age and preexisting hearing problems.

The lack of real-world practice patterns for monitoring ototoxicity makes identifying effective prevention and intervention strategies challenging, say the authors, led by Asmi Chattaraj, MD, of the University of Pittsburgh Medical Center (UPMC), McKeesport, Pa.

The team conducted a survey of oncologists with the UPMC Hillman Cancer Center network regarding patterns for monitoring and reducing the risk of ototoxicity.

Of the 35 responding oncologists, the majority (97%) indicated that they regularly discuss the risk of ototoxicity with all patients before they receive cisplatin. However, only 18% of the respondents said they obtain audiograms for patients before administering cisplatin, 69% order audiograms only if patients complain of hearing loss or tinnitus, and 35% of respondents do not perform regular monitoring for ototoxicity.

“This heterogeneity of practice within a single network highlights the need for high-quality evidence to guide clinical practice and the urgent need to standardize the necessary diagnostic steps to monitor for ototoxicity and its effect on the quality of life in the adult oncology practice, similar to the current practice in the pediatric patient population,” the researchers determined.
 

Proactive rather than reactive

Managing cisplatin-induced ototoxicity “must be viewed as a proactive measure rather than a reactive measure,” Nisha A. Mohindra, MD, wrote in an accompanying editorial.

Dr. Mohindra noted that although it is recommended that audiology assessments be conducted before, during, and after administration of ototoxicity drugs, the monitoring for ototoxicity remains underutilized in clinical practice. The path to better outcomes begins with implementing testing into clinical practice, she suggested.

“The most effective mechanism to manage ototoxicity currently is to identify patients at risk and implement programs to support ongoing monitoring,” Dr. Mohindra wrote.

“Even if ototoxicity cannot be prevented in some patients, providing treating oncologists with a timely opportunity to alter therapy or providing patients with support, guidance, and earlier access to rehabilitation services may mitigate long-term effects of hearing loss,” she concluded.

The researchers have disclosed numerous relationships with industry, a full listing of which is available with the original article.

A version of this article first appeared on Medscape.com.

Cisplatin is one of the most commonly used chemotherapeutic agents for treating a variety of cancers, such as lung, bladder, and ovarian cancers. But the therapy comes with a drawback – ototoxicity.

“More than half of adult and pediatric patients with cancer treated with cisplatin developed hearing impairment with major impact on patients’ health-related quality of life,” researchers noted in a clinical review published in JCO Oncology Practice.

It is estimated that 36% of adult patients and 40%-60% of pediatric patients experience cisplatin-induced ototoxicity. It can present as tinnitus (ringing in the ears), loss of hearing in the high-frequency range (4000 – 8000 Hz), or, at late stages, a decrease in the ability to hear lower frequencies.

The incidence of cisplatin-induced ototoxicity is estimated to be 36% of adult patients and 40% to 60% of pediatric patients. Ototoxicity can present as tinnitus, loss of hearing in the high-frequency range (4,000-8,000 Hz), or, at late stages, a decrease in the ability to hear lower frequencies.

The risk of developing cisplatin-induced ototoxicity depends on various factors, including the cumulative dose of cisplatin, the duration of treatment, and individual patient factors, such as age and preexisting hearing problems.

The lack of real-world practice patterns for monitoring ototoxicity makes identifying effective prevention and intervention strategies challenging, say the authors, led by Asmi Chattaraj, MD, of the University of Pittsburgh Medical Center (UPMC), McKeesport, Pa.

The team conducted a survey of oncologists with the UPMC Hillman Cancer Center network regarding patterns for monitoring and reducing the risk of ototoxicity.

Of the 35 responding oncologists, the majority (97%) indicated that they regularly discuss the risk of ototoxicity with all patients before they receive cisplatin. However, only 18% of the respondents said they obtain audiograms for patients before administering cisplatin, 69% order audiograms only if patients complain of hearing loss or tinnitus, and 35% of respondents do not perform regular monitoring for ototoxicity.

“This heterogeneity of practice within a single network highlights the need for high-quality evidence to guide clinical practice and the urgent need to standardize the necessary diagnostic steps to monitor for ototoxicity and its effect on the quality of life in the adult oncology practice, similar to the current practice in the pediatric patient population,” the researchers determined.
 

Proactive rather than reactive

Managing cisplatin-induced ototoxicity “must be viewed as a proactive measure rather than a reactive measure,” Nisha A. Mohindra, MD, wrote in an accompanying editorial.

Dr. Mohindra noted that although it is recommended that audiology assessments be conducted before, during, and after administration of ototoxicity drugs, the monitoring for ototoxicity remains underutilized in clinical practice. The path to better outcomes begins with implementing testing into clinical practice, she suggested.

“The most effective mechanism to manage ototoxicity currently is to identify patients at risk and implement programs to support ongoing monitoring,” Dr. Mohindra wrote.

“Even if ototoxicity cannot be prevented in some patients, providing treating oncologists with a timely opportunity to alter therapy or providing patients with support, guidance, and earlier access to rehabilitation services may mitigate long-term effects of hearing loss,” she concluded.

The researchers have disclosed numerous relationships with industry, a full listing of which is available with the original article.

A version of this article first appeared on Medscape.com.

Cisplatin is one of the most commonly used chemotherapeutic agents for treating a variety of cancers, such as lung, bladder, and ovarian cancers. But the therapy comes with a drawback – ototoxicity.

“More than half of adult and pediatric patients with cancer treated with cisplatin developed hearing impairment with major impact on patients’ health-related quality of life,” researchers noted in a clinical review published in JCO Oncology Practice.

It is estimated that 36% of adult patients and 40%-60% of pediatric patients experience cisplatin-induced ototoxicity. It can present as tinnitus (ringing in the ears), loss of hearing in the high-frequency range (4000 – 8000 Hz), or, at late stages, a decrease in the ability to hear lower frequencies.

The incidence of cisplatin-induced ototoxicity is estimated to be 36% of adult patients and 40% to 60% of pediatric patients. Ototoxicity can present as tinnitus, loss of hearing in the high-frequency range (4,000-8,000 Hz), or, at late stages, a decrease in the ability to hear lower frequencies.

The risk of developing cisplatin-induced ototoxicity depends on various factors, including the cumulative dose of cisplatin, the duration of treatment, and individual patient factors, such as age and preexisting hearing problems.

The lack of real-world practice patterns for monitoring ototoxicity makes identifying effective prevention and intervention strategies challenging, say the authors, led by Asmi Chattaraj, MD, of the University of Pittsburgh Medical Center (UPMC), McKeesport, Pa.

The team conducted a survey of oncologists with the UPMC Hillman Cancer Center network regarding patterns for monitoring and reducing the risk of ototoxicity.

Of the 35 responding oncologists, the majority (97%) indicated that they regularly discuss the risk of ototoxicity with all patients before they receive cisplatin. However, only 18% of the respondents said they obtain audiograms for patients before administering cisplatin, 69% order audiograms only if patients complain of hearing loss or tinnitus, and 35% of respondents do not perform regular monitoring for ototoxicity.

“This heterogeneity of practice within a single network highlights the need for high-quality evidence to guide clinical practice and the urgent need to standardize the necessary diagnostic steps to monitor for ototoxicity and its effect on the quality of life in the adult oncology practice, similar to the current practice in the pediatric patient population,” the researchers determined.
 

Proactive rather than reactive

Managing cisplatin-induced ototoxicity “must be viewed as a proactive measure rather than a reactive measure,” Nisha A. Mohindra, MD, wrote in an accompanying editorial.

Dr. Mohindra noted that although it is recommended that audiology assessments be conducted before, during, and after administration of ototoxicity drugs, the monitoring for ototoxicity remains underutilized in clinical practice. The path to better outcomes begins with implementing testing into clinical practice, she suggested.

“The most effective mechanism to manage ototoxicity currently is to identify patients at risk and implement programs to support ongoing monitoring,” Dr. Mohindra wrote.

“Even if ototoxicity cannot be prevented in some patients, providing treating oncologists with a timely opportunity to alter therapy or providing patients with support, guidance, and earlier access to rehabilitation services may mitigate long-term effects of hearing loss,” she concluded.

The researchers have disclosed numerous relationships with industry, a full listing of which is available with the original article.

A version of this article first appeared on Medscape.com.

ORLANDO – Patients with hepatocellular carcinoma (HCC) who undergo surgery or thermal ablation with curative intent are at high risk for recurrence, but currently, no adjuvant therapy standard of care exists for these patients.

New findings signal a promising option for these patients. The combination of the immune checkpoint inhibitor atezolizumab (Tecentriq) and the angiogenesis inhibitor bevacizumab (Avastin) was associated with a significant improvement in recurrence-free survival, compared with active surveillance, and represents the first option to show efficacy in the adjuvant setting following surgical resection of HCCs for patients at high risk for recurrence.

The recurrence-free survival benefit corresponded to a 28% reduced risk of recurrence or death among patients who received the combination therapy in comparison with active surveillance. However, the overall survival data remain immature.

The data come from an interim analysis of the IMbrave050 trial, which was presented at the annual meeting of the American Association for Cancer Research.

“Atezolizumab plus bevacizumab may be a practice-changing adjuvant treatment options for patients with high-risk HCC,” said lead investigator Pierce Chow, MBBS, PhD, codirector of the National Cancer Centre Singapore Comprehensive Liver Cancer Clinic. He presented the results in an oral abstract session at the meeting. The combination “may also change clinical indications for surgical resection” because clinicians may be more likely to consider resection for patients at extremely high risk for recurrence if the risk of recurrence can be reduced with this combination.

In the previous IMbrave150 trial, the combination of atezolizumab and bevacizumab significantly improved outcomes for patients with high-risk and non–high-risk unresectable HCC, compared with the standard of care sorafenib (Nexavar).

In that trial, the median overall survival in the intention-to-treat population was 19.2 months for patients who received atezolizumab-bevacizumab versus 13.4 months for patients who received sorafenib (P = .0009).

The combination was also associated with improvements in progression-free survival and objective response rates, compared with sorafenib.

On the basis of these results, the IMbrave050 investigators explored whether the same benefits would occur for patients with resectable disease considered to be at high risk for recurrence owing to tumor size, vascular invasion, or poor tumor differentiation. The trial compared the combination for 334 patients with active surveillance, also for 334 patients, in the adjuvant setting.

Patients were considered good candidates for thermal ablation if they had a single tumor greater than 2 cm, but not larger than 5 cm in its longest dimension, or if they had four or fewer tumors, all of which were no larger than 5 cm. For all other patients, surgical resection was recommended.

The median age of the patients was 60. For about half of patients in each arm, the expression level of programmed death–ligand-1 (PD-L1) was 1% or higher.

After a median follow-up of 17.4 months, the 12-month recurrence-free survival rate, as assessed by independent review, was 78% for patients in the treatment arm, compared with 65% for patients who were assigned to active surveillance (hazard ratio, 0.72; P = .012). This finding was generally consistent across clinical subgroups, including groups based on age, sex, race/ethnicity, performance status, PD-L1 expression, number of high-risk features, Barcelona Clinic Liver Cancer stage, cancer etiology, procedure type, microvascular invasion, or tumor numbers and size.

Of 133 patients on active surveillance who experienced a protocol-defined recurrence event, 81 (61%) crossed over to the atezolizumab/bevacizumab arm.

The overall survival benefit of the combination therapy was less clear. Dr. Chow called the overall survival data “highly immature” at the time of data cutoff.

Overall, 47 patients died – 7 more in the combination arm (27 vs. 20). More specifically, 17 patients in the combination arm and 16 on active surveillance died from progressive disease; 6 patients in the treatment arm versus 1 on surveillance died from adverse events. The remaining deaths were attributed to other causes. Two deaths in the combination arm were considered treatment related, one from esophageal varices hemorrhage, and the other from ischemic stroke.

Dr. Chow said a number of deaths attributed to HCC recurrence was similar between the groups. There were three COVID-19–related deaths within 1 year of randomization, all in the combination arm.

As for adverse events, the safety of the combination was largely consistent with that reported in the IMbrave150 trial. Nearly all patients experienced at least one adverse event. Treatment-related grade 3 or 4 adverse events occurred in 34.9% of patients in the combination group, and serious treatment-related events occurred in 13.3%.

The most common adverse events of any grade were proteinuria, hypertension, decreased platelet count, increases in liver enzyme level, hypothyroidism, arthralgia, pruritus, rash, increase in serum bilirubin level, and fever.

Invited discussant Stephen L. Chan, MD, from the Chinese University of Hong Kong, said the study was “definitely” relevant to clinicians and addresses “a very important unmet need.”

Dr. Chan noted that he thinks this combination will “likely” be practice changing, given the improvement in recurrence-free survival, but “certainly we need more data to guide us in patient selection.”

The study was funded by F. Hoffman–La Roche. Dr. Chow has consulting for and has received honoraria and grant/research support from Roche and others. Dr. Chan has received honoraria from Roche and consulting fees and grant/research support from others.

A version of this article first appeared on Medscape.com.

ORLANDO – Patients with hepatocellular carcinoma (HCC) who undergo surgery or thermal ablation with curative intent are at high risk for recurrence, but currently, no adjuvant therapy standard of care exists for these patients.

New findings signal a promising option for these patients. The combination of the immune checkpoint inhibitor atezolizumab (Tecentriq) and the angiogenesis inhibitor bevacizumab (Avastin) was associated with a significant improvement in recurrence-free survival, compared with active surveillance, and represents the first option to show efficacy in the adjuvant setting following surgical resection of HCCs for patients at high risk for recurrence.

The recurrence-free survival benefit corresponded to a 28% reduced risk of recurrence or death among patients who received the combination therapy in comparison with active surveillance. However, the overall survival data remain immature.

The data come from an interim analysis of the IMbrave050 trial, which was presented at the annual meeting of the American Association for Cancer Research.

“Atezolizumab plus bevacizumab may be a practice-changing adjuvant treatment options for patients with high-risk HCC,” said lead investigator Pierce Chow, MBBS, PhD, codirector of the National Cancer Centre Singapore Comprehensive Liver Cancer Clinic. He presented the results in an oral abstract session at the meeting. The combination “may also change clinical indications for surgical resection” because clinicians may be more likely to consider resection for patients at extremely high risk for recurrence if the risk of recurrence can be reduced with this combination.

In the previous IMbrave150 trial, the combination of atezolizumab and bevacizumab significantly improved outcomes for patients with high-risk and non–high-risk unresectable HCC, compared with the standard of care sorafenib (Nexavar).

In that trial, the median overall survival in the intention-to-treat population was 19.2 months for patients who received atezolizumab-bevacizumab versus 13.4 months for patients who received sorafenib (P = .0009).

The combination was also associated with improvements in progression-free survival and objective response rates, compared with sorafenib.

On the basis of these results, the IMbrave050 investigators explored whether the same benefits would occur for patients with resectable disease considered to be at high risk for recurrence owing to tumor size, vascular invasion, or poor tumor differentiation. The trial compared the combination for 334 patients with active surveillance, also for 334 patients, in the adjuvant setting.

Patients were considered good candidates for thermal ablation if they had a single tumor greater than 2 cm, but not larger than 5 cm in its longest dimension, or if they had four or fewer tumors, all of which were no larger than 5 cm. For all other patients, surgical resection was recommended.

The median age of the patients was 60. For about half of patients in each arm, the expression level of programmed death–ligand-1 (PD-L1) was 1% or higher.

After a median follow-up of 17.4 months, the 12-month recurrence-free survival rate, as assessed by independent review, was 78% for patients in the treatment arm, compared with 65% for patients who were assigned to active surveillance (hazard ratio, 0.72; P = .012). This finding was generally consistent across clinical subgroups, including groups based on age, sex, race/ethnicity, performance status, PD-L1 expression, number of high-risk features, Barcelona Clinic Liver Cancer stage, cancer etiology, procedure type, microvascular invasion, or tumor numbers and size.

Of 133 patients on active surveillance who experienced a protocol-defined recurrence event, 81 (61%) crossed over to the atezolizumab/bevacizumab arm.

The overall survival benefit of the combination therapy was less clear. Dr. Chow called the overall survival data “highly immature” at the time of data cutoff.

Overall, 47 patients died – 7 more in the combination arm (27 vs. 20). More specifically, 17 patients in the combination arm and 16 on active surveillance died from progressive disease; 6 patients in the treatment arm versus 1 on surveillance died from adverse events. The remaining deaths were attributed to other causes. Two deaths in the combination arm were considered treatment related, one from esophageal varices hemorrhage, and the other from ischemic stroke.

Dr. Chow said a number of deaths attributed to HCC recurrence was similar between the groups. There were three COVID-19–related deaths within 1 year of randomization, all in the combination arm.

As for adverse events, the safety of the combination was largely consistent with that reported in the IMbrave150 trial. Nearly all patients experienced at least one adverse event. Treatment-related grade 3 or 4 adverse events occurred in 34.9% of patients in the combination group, and serious treatment-related events occurred in 13.3%.

The most common adverse events of any grade were proteinuria, hypertension, decreased platelet count, increases in liver enzyme level, hypothyroidism, arthralgia, pruritus, rash, increase in serum bilirubin level, and fever.

Invited discussant Stephen L. Chan, MD, from the Chinese University of Hong Kong, said the study was “definitely” relevant to clinicians and addresses “a very important unmet need.”

Dr. Chan noted that he thinks this combination will “likely” be practice changing, given the improvement in recurrence-free survival, but “certainly we need more data to guide us in patient selection.”

The study was funded by F. Hoffman–La Roche. Dr. Chow has consulting for and has received honoraria and grant/research support from Roche and others. Dr. Chan has received honoraria from Roche and consulting fees and grant/research support from others.

A version of this article first appeared on Medscape.com.

ORLANDO – Patients with hepatocellular carcinoma (HCC) who undergo surgery or thermal ablation with curative intent are at high risk for recurrence, but currently, no adjuvant therapy standard of care exists for these patients.

New findings signal a promising option for these patients. The combination of the immune checkpoint inhibitor atezolizumab (Tecentriq) and the angiogenesis inhibitor bevacizumab (Avastin) was associated with a significant improvement in recurrence-free survival, compared with active surveillance, and represents the first option to show efficacy in the adjuvant setting following surgical resection of HCCs for patients at high risk for recurrence.

The recurrence-free survival benefit corresponded to a 28% reduced risk of recurrence or death among patients who received the combination therapy in comparison with active surveillance. However, the overall survival data remain immature.

The data come from an interim analysis of the IMbrave050 trial, which was presented at the annual meeting of the American Association for Cancer Research.

“Atezolizumab plus bevacizumab may be a practice-changing adjuvant treatment options for patients with high-risk HCC,” said lead investigator Pierce Chow, MBBS, PhD, codirector of the National Cancer Centre Singapore Comprehensive Liver Cancer Clinic. He presented the results in an oral abstract session at the meeting. The combination “may also change clinical indications for surgical resection” because clinicians may be more likely to consider resection for patients at extremely high risk for recurrence if the risk of recurrence can be reduced with this combination.

In the previous IMbrave150 trial, the combination of atezolizumab and bevacizumab significantly improved outcomes for patients with high-risk and non–high-risk unresectable HCC, compared with the standard of care sorafenib (Nexavar).

In that trial, the median overall survival in the intention-to-treat population was 19.2 months for patients who received atezolizumab-bevacizumab versus 13.4 months for patients who received sorafenib (P = .0009).

The combination was also associated with improvements in progression-free survival and objective response rates, compared with sorafenib.

On the basis of these results, the IMbrave050 investigators explored whether the same benefits would occur for patients with resectable disease considered to be at high risk for recurrence owing to tumor size, vascular invasion, or poor tumor differentiation. The trial compared the combination for 334 patients with active surveillance, also for 334 patients, in the adjuvant setting.

Patients were considered good candidates for thermal ablation if they had a single tumor greater than 2 cm, but not larger than 5 cm in its longest dimension, or if they had four or fewer tumors, all of which were no larger than 5 cm. For all other patients, surgical resection was recommended.

The median age of the patients was 60. For about half of patients in each arm, the expression level of programmed death–ligand-1 (PD-L1) was 1% or higher.

After a median follow-up of 17.4 months, the 12-month recurrence-free survival rate, as assessed by independent review, was 78% for patients in the treatment arm, compared with 65% for patients who were assigned to active surveillance (hazard ratio, 0.72; P = .012). This finding was generally consistent across clinical subgroups, including groups based on age, sex, race/ethnicity, performance status, PD-L1 expression, number of high-risk features, Barcelona Clinic Liver Cancer stage, cancer etiology, procedure type, microvascular invasion, or tumor numbers and size.

Of 133 patients on active surveillance who experienced a protocol-defined recurrence event, 81 (61%) crossed over to the atezolizumab/bevacizumab arm.

The overall survival benefit of the combination therapy was less clear. Dr. Chow called the overall survival data “highly immature” at the time of data cutoff.

Overall, 47 patients died – 7 more in the combination arm (27 vs. 20). More specifically, 17 patients in the combination arm and 16 on active surveillance died from progressive disease; 6 patients in the treatment arm versus 1 on surveillance died from adverse events. The remaining deaths were attributed to other causes. Two deaths in the combination arm were considered treatment related, one from esophageal varices hemorrhage, and the other from ischemic stroke.

Dr. Chow said a number of deaths attributed to HCC recurrence was similar between the groups. There were three COVID-19–related deaths within 1 year of randomization, all in the combination arm.

As for adverse events, the safety of the combination was largely consistent with that reported in the IMbrave150 trial. Nearly all patients experienced at least one adverse event. Treatment-related grade 3 or 4 adverse events occurred in 34.9% of patients in the combination group, and serious treatment-related events occurred in 13.3%.

The most common adverse events of any grade were proteinuria, hypertension, decreased platelet count, increases in liver enzyme level, hypothyroidism, arthralgia, pruritus, rash, increase in serum bilirubin level, and fever.

Invited discussant Stephen L. Chan, MD, from the Chinese University of Hong Kong, said the study was “definitely” relevant to clinicians and addresses “a very important unmet need.”

Dr. Chan noted that he thinks this combination will “likely” be practice changing, given the improvement in recurrence-free survival, but “certainly we need more data to guide us in patient selection.”

The study was funded by F. Hoffman–La Roche. Dr. Chow has consulting for and has received honoraria and grant/research support from Roche and others. Dr. Chan has received honoraria from Roche and consulting fees and grant/research support from others.

A version of this article first appeared on Medscape.com.