Patient & Survivor Care

TOPLINE:

Compared with six cycles, three cycles of chemotherapy for high-risk retinoblastoma showed noninferior 5-year disease-free survival (DFS). The three-cycle regimen also resulted in fewer adverse events and lower costs.

METHODOLOGY:

• The introduction of chemotherapy has increased survival rates for patients with retinoblastoma, but the optimal number of postoperative adjuvant cycles remains unclear due to scant randomized clinical trial data for high-risk patients.
• In the new trial, participants at two premier eye centers in China were randomly assigned to receive either three (n = 94) or six (n = 93) cycles of carboplatin, etoposide, and vincristine (CEV) chemotherapy after enucleation.
• The primary endpoint was 5-year DFS, and the secondary endpoints were overall survival, safety, economic burden, and quality of life.
• Patients were followed up every 3 months for the first 2 years and then every 6 months thereafter, with a median follow-up of 79 months.
• Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).

TAKEAWAY:

• The 5-year DFS rates were 90.4% and 89.2% for the three- and six-cycle groups, respectively, meeting the noninferiority criterion (P = .003).
• The six-cycle group experienced a higher frequency of adverse events, including neutropenia, anemia, and nausea, than the three-cycle group.
• The quality-of-life scores were higher in the three-cycle group, particularly in physical, emotional, and social functioning parameters.
• The total, direct, and indirect costs were significantly lower in the three-cycle group than in the six-cycle group.

IN PRACTICE:

“A three-cycle CEV regimen demonstrated noninferiority, compared with a six-cycle approach, and was and proved to be an efficacious adjuvant chemotherapy regimen for individuals diagnosed with pathologically high-risk retinoblastoma,” the authors of the study wrote.

In an accompanying editorial, Ning Li, MD, and colleagues wrote that the findings “could lead to changes in clinical practice, reducing treatment burden and costs without compromising patient outcomes.”
 

SOURCE:

This study was led by Huijing Ye, MD, PhD, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University in Guangzhou, China. Both the study and editorial were published online in JAMA.

LIMITATIONS: 

The open-label design of the study might introduce bias, although an independent, blinded committee evaluated the clinical outcomes. The 12% noninferiority margin was notably substantial, considering the rarity of retinoblastoma and the wide range of survival rates. The criteria for adjuvant therapy, especially regarding choroidal invasion, were debatable and required further follow-up to clarify the prognosis related to various pathologic features.

DISCLOSURES:

This study was supported by the Sun Yat-Sen University Clinical Research 5010 Program and the Shanghai Committee of Science and Technology. No relevant conflict of interest was disclosed by the authors of the paper or the editorial.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Compared with six cycles, three cycles of chemotherapy for high-risk retinoblastoma showed noninferior 5-year disease-free survival (DFS). The three-cycle regimen also resulted in fewer adverse events and lower costs.

METHODOLOGY:

• The introduction of chemotherapy has increased survival rates for patients with retinoblastoma, but the optimal number of postoperative adjuvant cycles remains unclear due to scant randomized clinical trial data for high-risk patients.
• In the new trial, participants at two premier eye centers in China were randomly assigned to receive either three (n = 94) or six (n = 93) cycles of carboplatin, etoposide, and vincristine (CEV) chemotherapy after enucleation.
• The primary endpoint was 5-year DFS, and the secondary endpoints were overall survival, safety, economic burden, and quality of life.
• Patients were followed up every 3 months for the first 2 years and then every 6 months thereafter, with a median follow-up of 79 months.
• Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).

TAKEAWAY:

• The 5-year DFS rates were 90.4% and 89.2% for the three- and six-cycle groups, respectively, meeting the noninferiority criterion (P = .003).
• The six-cycle group experienced a higher frequency of adverse events, including neutropenia, anemia, and nausea, than the three-cycle group.
• The quality-of-life scores were higher in the three-cycle group, particularly in physical, emotional, and social functioning parameters.
• The total, direct, and indirect costs were significantly lower in the three-cycle group than in the six-cycle group.

IN PRACTICE:

“A three-cycle CEV regimen demonstrated noninferiority, compared with a six-cycle approach, and was and proved to be an efficacious adjuvant chemotherapy regimen for individuals diagnosed with pathologically high-risk retinoblastoma,” the authors of the study wrote.

In an accompanying editorial, Ning Li, MD, and colleagues wrote that the findings “could lead to changes in clinical practice, reducing treatment burden and costs without compromising patient outcomes.”
 

SOURCE:

This study was led by Huijing Ye, MD, PhD, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University in Guangzhou, China. Both the study and editorial were published online in JAMA.

LIMITATIONS: 

The open-label design of the study might introduce bias, although an independent, blinded committee evaluated the clinical outcomes. The 12% noninferiority margin was notably substantial, considering the rarity of retinoblastoma and the wide range of survival rates. The criteria for adjuvant therapy, especially regarding choroidal invasion, were debatable and required further follow-up to clarify the prognosis related to various pathologic features.

DISCLOSURES:

This study was supported by the Sun Yat-Sen University Clinical Research 5010 Program and the Shanghai Committee of Science and Technology. No relevant conflict of interest was disclosed by the authors of the paper or the editorial.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Compared with six cycles, three cycles of chemotherapy for high-risk retinoblastoma showed noninferior 5-year disease-free survival (DFS). The three-cycle regimen also resulted in fewer adverse events and lower costs.

METHODOLOGY:

• The introduction of chemotherapy has increased survival rates for patients with retinoblastoma, but the optimal number of postoperative adjuvant cycles remains unclear due to scant randomized clinical trial data for high-risk patients.
• In the new trial, participants at two premier eye centers in China were randomly assigned to receive either three (n = 94) or six (n = 93) cycles of carboplatin, etoposide, and vincristine (CEV) chemotherapy after enucleation.
• The primary endpoint was 5-year DFS, and the secondary endpoints were overall survival, safety, economic burden, and quality of life.
• Patients were followed up every 3 months for the first 2 years and then every 6 months thereafter, with a median follow-up of 79 months.
• Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).

TAKEAWAY:

• The 5-year DFS rates were 90.4% and 89.2% for the three- and six-cycle groups, respectively, meeting the noninferiority criterion (P = .003).
• The six-cycle group experienced a higher frequency of adverse events, including neutropenia, anemia, and nausea, than the three-cycle group.
• The quality-of-life scores were higher in the three-cycle group, particularly in physical, emotional, and social functioning parameters.
• The total, direct, and indirect costs were significantly lower in the three-cycle group than in the six-cycle group.

IN PRACTICE:

“A three-cycle CEV regimen demonstrated noninferiority, compared with a six-cycle approach, and was and proved to be an efficacious adjuvant chemotherapy regimen for individuals diagnosed with pathologically high-risk retinoblastoma,” the authors of the study wrote.

In an accompanying editorial, Ning Li, MD, and colleagues wrote that the findings “could lead to changes in clinical practice, reducing treatment burden and costs without compromising patient outcomes.”
 

SOURCE:

This study was led by Huijing Ye, MD, PhD, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University in Guangzhou, China. Both the study and editorial were published online in JAMA.

LIMITATIONS: 

The open-label design of the study might introduce bias, although an independent, blinded committee evaluated the clinical outcomes. The 12% noninferiority margin was notably substantial, considering the rarity of retinoblastoma and the wide range of survival rates. The criteria for adjuvant therapy, especially regarding choroidal invasion, were debatable and required further follow-up to clarify the prognosis related to various pathologic features.

DISCLOSURES:

This study was supported by the Sun Yat-Sen University Clinical Research 5010 Program and the Shanghai Committee of Science and Technology. No relevant conflict of interest was disclosed by the authors of the paper or the editorial.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

SAN FRANCISCO — While the physical toll of cancer is well documented, the financial toll can also be severe and lasting.

Overall, patients with cancer tend to face higher rates of debt collection, medical collections, and bankruptcies, as well as lower credit scores, according to two new studies presented at the American College of Surgeons Clinical Congress 2024.

“These are the first studies to provide numerical evidence of financial toxicity among cancer survivors,” Benjamin C. James, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, Massachusetts, who worked on both studies, said in a statement. “Previous data on this topic largely relies on subjective survey reviews.”

In one study, researchers used the Massachusetts Cancer Registry to identify 99,175 patients diagnosed with cancer between 2010 and 2019 and matched them with 188,875 control individuals without cancer. Researchers then assessed financial toxicity using Experian credit bureau data for participants.

Overall, patients with cancer faced a range of financial challenges that often lasted years following their diagnosis.

Patients were nearly five times more likely to experience bankruptcy and had average credit scores nearly 80 points lower than control individuals without cancer. The drop in credit scores was more pronounced for survivors of bladder, liver, lung, and colorectal cancer (CRC) and persisted for up to 9.5 years.

For certain cancer types, in particular, “we are looking years after a diagnosis, and we see that the credit score goes down and it never comes back up,” James said.

The other study, which used a sample of 7227 patients with CRC from Massachusetts, identified several factors that correlated with lower credit scores.

Compared with patients who only had surgery, peers who underwent radiation only experienced a 62-point drop in their credit score after their diagnosis, while those who had chemotherapy alone had just over a 14-point drop in their credit score. Among patients who had combination treatments, those who underwent both surgery and radiation experienced a nearly 16-point drop in their credit score and those who had surgery and chemoradiation actually experienced a 2.59 bump, compared with those who had surgery alone.

Financial toxicity was worse for patients younger than 62 years, those identifying as Black or Hispanic individuals, unmarried individuals, those with an annual income below $52,000, and those living in deprived areas.

The studies add to findings from the 2015 North American Thyroid Cancer Survivorship Study, which reported that 50% of thyroid cancer survivors encountered financial toxicity because of their diagnosis.

James said the persistent financial strain of cancer care, even in a state like Massachusetts, which mandates universal healthcare, underscores the need for “broader policy changes and reforms, including reconsidering debt collection practices.”

“Financial security should be a priority in cancer care,” he added.

The studies had no specific funding. The authors have disclosed no relevant conflict of interest.

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

SAN FRANCISCO — While the physical toll of cancer is well documented, the financial toll can also be severe and lasting.

Overall, patients with cancer tend to face higher rates of debt collection, medical collections, and bankruptcies, as well as lower credit scores, according to two new studies presented at the American College of Surgeons Clinical Congress 2024.

“These are the first studies to provide numerical evidence of financial toxicity among cancer survivors,” Benjamin C. James, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, Massachusetts, who worked on both studies, said in a statement. “Previous data on this topic largely relies on subjective survey reviews.”

In one study, researchers used the Massachusetts Cancer Registry to identify 99,175 patients diagnosed with cancer between 2010 and 2019 and matched them with 188,875 control individuals without cancer. Researchers then assessed financial toxicity using Experian credit bureau data for participants.

Overall, patients with cancer faced a range of financial challenges that often lasted years following their diagnosis.

Patients were nearly five times more likely to experience bankruptcy and had average credit scores nearly 80 points lower than control individuals without cancer. The drop in credit scores was more pronounced for survivors of bladder, liver, lung, and colorectal cancer (CRC) and persisted for up to 9.5 years.

For certain cancer types, in particular, “we are looking years after a diagnosis, and we see that the credit score goes down and it never comes back up,” James said.

The other study, which used a sample of 7227 patients with CRC from Massachusetts, identified several factors that correlated with lower credit scores.

Compared with patients who only had surgery, peers who underwent radiation only experienced a 62-point drop in their credit score after their diagnosis, while those who had chemotherapy alone had just over a 14-point drop in their credit score. Among patients who had combination treatments, those who underwent both surgery and radiation experienced a nearly 16-point drop in their credit score and those who had surgery and chemoradiation actually experienced a 2.59 bump, compared with those who had surgery alone.

Financial toxicity was worse for patients younger than 62 years, those identifying as Black or Hispanic individuals, unmarried individuals, those with an annual income below $52,000, and those living in deprived areas.

The studies add to findings from the 2015 North American Thyroid Cancer Survivorship Study, which reported that 50% of thyroid cancer survivors encountered financial toxicity because of their diagnosis.

James said the persistent financial strain of cancer care, even in a state like Massachusetts, which mandates universal healthcare, underscores the need for “broader policy changes and reforms, including reconsidering debt collection practices.”

“Financial security should be a priority in cancer care,” he added.

The studies had no specific funding. The authors have disclosed no relevant conflict of interest.

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

SAN FRANCISCO — While the physical toll of cancer is well documented, the financial toll can also be severe and lasting.

Overall, patients with cancer tend to face higher rates of debt collection, medical collections, and bankruptcies, as well as lower credit scores, according to two new studies presented at the American College of Surgeons Clinical Congress 2024.

“These are the first studies to provide numerical evidence of financial toxicity among cancer survivors,” Benjamin C. James, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, Massachusetts, who worked on both studies, said in a statement. “Previous data on this topic largely relies on subjective survey reviews.”

In one study, researchers used the Massachusetts Cancer Registry to identify 99,175 patients diagnosed with cancer between 2010 and 2019 and matched them with 188,875 control individuals without cancer. Researchers then assessed financial toxicity using Experian credit bureau data for participants.

Overall, patients with cancer faced a range of financial challenges that often lasted years following their diagnosis.

Patients were nearly five times more likely to experience bankruptcy and had average credit scores nearly 80 points lower than control individuals without cancer. The drop in credit scores was more pronounced for survivors of bladder, liver, lung, and colorectal cancer (CRC) and persisted for up to 9.5 years.

For certain cancer types, in particular, “we are looking years after a diagnosis, and we see that the credit score goes down and it never comes back up,” James said.

The other study, which used a sample of 7227 patients with CRC from Massachusetts, identified several factors that correlated with lower credit scores.

Compared with patients who only had surgery, peers who underwent radiation only experienced a 62-point drop in their credit score after their diagnosis, while those who had chemotherapy alone had just over a 14-point drop in their credit score. Among patients who had combination treatments, those who underwent both surgery and radiation experienced a nearly 16-point drop in their credit score and those who had surgery and chemoradiation actually experienced a 2.59 bump, compared with those who had surgery alone.

Financial toxicity was worse for patients younger than 62 years, those identifying as Black or Hispanic individuals, unmarried individuals, those with an annual income below $52,000, and those living in deprived areas.

The studies add to findings from the 2015 North American Thyroid Cancer Survivorship Study, which reported that 50% of thyroid cancer survivors encountered financial toxicity because of their diagnosis.

James said the persistent financial strain of cancer care, even in a state like Massachusetts, which mandates universal healthcare, underscores the need for “broader policy changes and reforms, including reconsidering debt collection practices.”

“Financial security should be a priority in cancer care,” he added.

The studies had no specific funding. The authors have disclosed no relevant conflict of interest.

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

For more than three decades, the federal government sought to make amends to countless Americans who developed cancer after being exposed to radiation from nuclear testing in the Southwest or while working in the uranium mining industry.

As of 2022, more than 40,000 patients with cancer successfully applied for $2.6 billion in compensation. Recipients included “downwinders” who were eligible for $50,000 each if they lived in certain areas of Nevada, Utah, and Arizona during specified nuclear testing periods and developed a covered form of cancer.

In June 2024, however, the Radiation Exposure Compensation Program expired amid infighting among Republicans in Congress over whether to expand it. For now, no one can make a claim, even though many downwinders are still alive and continue to be diagnosed with covered cancers decades after they were exposed in the 1940s, 1950s, and 1960s.

There’s a glimmer of good news. The federal government continues to support free medical screenings for eligible people, including certain downwinders and uranium workers. Meanwhile, there are still important roles for clinicians across the country to play as politicians figure out what — if anything — to do next regarding those exposed to radiation.

“We are still here. We can still screen people,” Zachary Davis, program director for the Radiation Exposure Screening and Education Program, The University of New Mexico, in Albuquerque, New Mexico, said in an interview.
 

Still-Unfolding Legacy of Radiation Exposure

No one knew just how far radiation would spread when the first nuclear bomb was tested in New Mexico in July 1945. Would it cover the state? The entire Southwest? The whole nation?

It also wasn’t clear how radiation would affect people’s health. “There was an awareness that some cancers were caused by radiation, but there wasn’t a cohesive understanding of what the problem was,” Joseph Shonka, PhD, a health physicist who studies radiation exposure and has worked for decades in nuclear engineering, said in an interview.

Now, nearly eight decades later, scientists are still figuring out the full extent of radioactive fallout from nuclear testing. Just last year, a study suggested that radiation from 94 nuclear weapon tests in the Southwest from 1945 to 1962 reached 46 states along with Canada and Mexico.

Activists believe the tests triggered untold number of cancer cases in residents who were exposed in downwind areas:

“My brother died of stomach cancer; my mom died of bone cancer. One of my sisters is surviving brain tumors, and the other one is surviving thyroid cancer,” one New Mexico man recently told ABC-TV’s “Nightline.”

In Idaho, a downwinder advocate told Idaho Capital Sun that everyone who attended a reception for her newly married parents in 1952 — just weeks after a nuclear test — developed cancer or “weird medical complications.” That included her parents, who both had cancer. Her two older brothers, born in 1953 and 1955, also developed cancer, and she’s tracked many other cases in the small town of Emmett.

In Utah, another downwinder advocate told Utah News Dispatch that cancer was common in Salt Lake City neighborhood, where she grew up, which was exposed to fallout. She developed thyroid cancer, her younger sister developed stomach cancer, and an older sister died of lupus, which is connected to radiation exposure. But Salt Lake City isn’t in one of the regions of Utah covered by the federal compensation program, so the advocate can’t get a $50,000 payment.

Downwinders who lived in New Mexico, Idaho, and the Salt Lake City area of Utah are not covered by the federal compensation program. That means none of these people or their descendants are eligible for payments — yet.
 

Decades After Nuclear Testing, the Government Responds

In 1990, Congress passed the Radiation Exposure Compensation Act, which allowed compensation to people with cancer at several levels. It was later expanded. Downwinders — including those who’ve moved elsewhere over the years — were eligible for $50,000. Onsite participants in nuclear testing could get $75,000. Uranium miners, millers, and ore transporters in 11 states west of the Mississippi River could get $100,000.

Among downwinders, eligible cancers included blood cancers (leukemias with the exception of chronic lymphocytic leukemia, multiple myeloma, and non-Hodgkin’s lymphomas) and a long list of solid organ cancers such as thyroid, breast, stomach, brain, lung, colon, and liver cancers.

“When it comes to blood-related cancers, we do see leukemias, lymphomas, and multiple myeloma, but these cancers were more likely to occur sooner after fallout exposure,” said Laura Shaw, MD, principal investigator who oversees the radiation exposure screening program at the University of Nevada, Las Vegas. “At this point, we see more pancreatic, thyroid, lung, stomach, bladder, and breast cancer.”

The compensation program had major limitations, critics said. “It left out a lot of communities that were exposed,” said Lilly Adams, senior outreach coordinator with the Union of Concerned Scientists (UCS), which supports expanding the program. A national nonprofit organization, UCS was founded more than 50 years ago by scientists and students at the Massachusetts Institute of Technology.

“You have this pretty small amount of one-time compensation, and that’s it,” Adams said in an interview. “You can’t get reimbursed for medical costs or lost wages.” Still, “as flawed as the program is, it’s really valuable for the people who are eligible,” she noted.
 

Now Congress Is Divided on Next Steps

Some lawmakers have recognized the need to do more for those who developed cancer that’s potentially linked to radiation exposure. As the June 2024 expiration of the Radiation Exposure Compensation Act loomed, Democrats and Republicans in Congress worked together to extend and expand the program.

They introduced a bill for higher compensation — $100,000 per person — and the widening of covered downwinder areas to all of Arizona, Nevada, and Utah (which had only been partially covered), along with all of Colorado, Idaho, New Mexico, Montana, and Guam. Under the legislation, the program also would expand to cover some uranium workers who were on the job after 1971 and residents exposed to nuclear waste in Kentucky, Missouri, and Tennessee.

In March, the new legislation easily passed the US Senate by a vote of 69-30, with support from both political parties — but the Republican-led House hasn’t taken it up. As a result, the Radiation Exposure Compensation Act expired in June, and no one can submit new applications for compensation.

A spokesman for House Speaker Mike Johnson told Missouri Independent “unfortunately, the current Senate bill is estimated to cost $50-$60 billion in new mandatory spending with no offsets and was supported by only 20 of 49 Republicans in the Senate.”

Adams rejected these arguments. “The government spends literally trillions of dollars on our nuclear weapons. Whether or not you support that spending, the human cost of building those weapons should be factored in,” she said. She added that she hopes the House will act by the end of the year to pass the bill, but that’s uncertain.
 

As Compensation Is On Hold, Medical Screening Continues

A major benefit is still available for downwinders and uranium workers: Free medical screening and referrals for medical treatment. The Radiation Exposure Screening and Education Program’s funding has not been affected by the congressional impasse, so screenings are continuing for eligible people exposed to radiation.

Radiation exposure clinics offer screening in Arizona, Colorado, Nevada, New Mexico, and Utah, and health providers can get funding to offer screening in other affected states.

In Nevada, “we hold screening clinics throughout the state: Caliente, Ely, and Winnemucca. Also, in Reno and Las Vegas, which are not in designated downwind areas, but many downwinders have migrated there,” said Shaw in an interview. Among downwinders, “our youngest patients are in their 60s and range up to a few in their 90s,” she said.

Patients fill out questionnaires that ask about their medical problems, family history, and medications. “Ely patients in particular seem to have extensive family histories of cancer, and this may be due to their location directly downwind of the Nevada Test Site,” Shaw said. (Ely is a remote town in central eastern Nevada near the Utah border.)

The screenings cover both cancer and noncancer conditions. Shaw said clinicians often diagnose problems other than the covered cancers — new cases of atrial fibrillation, diabetes, and hypertension. “We see a ton of prostate and skin cancer” but don’t make patients eligible for the compensation program because they’re not covered, she said.

Even as compensation is on hold, doctors can get the word out that screenings are still available, Shaw said. “We continue to get contacted by individuals who in these communities who have never heard of this program, even though we’ve been holding clinics since 2005,” Shaw said. “Despite outreach activities and advertising through newspapers and radio, we find the most successful method of reaching these patients is through word of mouth — either from other patients or their doctors. That is why we feel it is so important to reach other physicians as well.”
 

Affected Patients Don’t Just Live in the West

On the outreach front, clinicians in states outside of the western US region can be helpful, too. Shaw urged oncologists nationwide to ask older patients where they lived in the 1950s and 1960s. “Did they live in Nevada, Arizona, Utah, and other Western states that are downwind? They may qualify for needed services and future compensation.”

With regard to compensation, she noted that applicants need to prove that they lived in affected areas many decades ago. And, of course, they must prove that they’ve had cancer. Locating residency records “has often been an enormous challenge.” Old utility bills, pay stubs, and high school annuals can be helpful, “but these records tend to disappear. People and their families throw stuff away.”

Even proving a cancer diagnosis can be a challenge because records can be missing. In Nevada, the law says clinicians only need to keep medical records for 5 years, Shaw said. “Imaging and pathology reports are destroyed. Patients that have been diagnosed with cancer can’t prove it.”

Shaw said she hopes oncologists will offer these messages to patients: “Be an advocate for your own health and keep copies of your own records. Discuss your diagnosis with your family and contact a cancer registry if you are diagnosed with cancer.”
 

A version of this article appeared on Medscape.com.

For more than three decades, the federal government sought to make amends to countless Americans who developed cancer after being exposed to radiation from nuclear testing in the Southwest or while working in the uranium mining industry.

As of 2022, more than 40,000 patients with cancer successfully applied for $2.6 billion in compensation. Recipients included “downwinders” who were eligible for $50,000 each if they lived in certain areas of Nevada, Utah, and Arizona during specified nuclear testing periods and developed a covered form of cancer.

In June 2024, however, the Radiation Exposure Compensation Program expired amid infighting among Republicans in Congress over whether to expand it. For now, no one can make a claim, even though many downwinders are still alive and continue to be diagnosed with covered cancers decades after they were exposed in the 1940s, 1950s, and 1960s.

There’s a glimmer of good news. The federal government continues to support free medical screenings for eligible people, including certain downwinders and uranium workers. Meanwhile, there are still important roles for clinicians across the country to play as politicians figure out what — if anything — to do next regarding those exposed to radiation.

“We are still here. We can still screen people,” Zachary Davis, program director for the Radiation Exposure Screening and Education Program, The University of New Mexico, in Albuquerque, New Mexico, said in an interview.
 

Still-Unfolding Legacy of Radiation Exposure

No one knew just how far radiation would spread when the first nuclear bomb was tested in New Mexico in July 1945. Would it cover the state? The entire Southwest? The whole nation?

It also wasn’t clear how radiation would affect people’s health. “There was an awareness that some cancers were caused by radiation, but there wasn’t a cohesive understanding of what the problem was,” Joseph Shonka, PhD, a health physicist who studies radiation exposure and has worked for decades in nuclear engineering, said in an interview.

Now, nearly eight decades later, scientists are still figuring out the full extent of radioactive fallout from nuclear testing. Just last year, a study suggested that radiation from 94 nuclear weapon tests in the Southwest from 1945 to 1962 reached 46 states along with Canada and Mexico.

Activists believe the tests triggered untold number of cancer cases in residents who were exposed in downwind areas:

“My brother died of stomach cancer; my mom died of bone cancer. One of my sisters is surviving brain tumors, and the other one is surviving thyroid cancer,” one New Mexico man recently told ABC-TV’s “Nightline.”

In Idaho, a downwinder advocate told Idaho Capital Sun that everyone who attended a reception for her newly married parents in 1952 — just weeks after a nuclear test — developed cancer or “weird medical complications.” That included her parents, who both had cancer. Her two older brothers, born in 1953 and 1955, also developed cancer, and she’s tracked many other cases in the small town of Emmett.

In Utah, another downwinder advocate told Utah News Dispatch that cancer was common in Salt Lake City neighborhood, where she grew up, which was exposed to fallout. She developed thyroid cancer, her younger sister developed stomach cancer, and an older sister died of lupus, which is connected to radiation exposure. But Salt Lake City isn’t in one of the regions of Utah covered by the federal compensation program, so the advocate can’t get a $50,000 payment.

Downwinders who lived in New Mexico, Idaho, and the Salt Lake City area of Utah are not covered by the federal compensation program. That means none of these people or their descendants are eligible for payments — yet.
 

Decades After Nuclear Testing, the Government Responds

In 1990, Congress passed the Radiation Exposure Compensation Act, which allowed compensation to people with cancer at several levels. It was later expanded. Downwinders — including those who’ve moved elsewhere over the years — were eligible for $50,000. Onsite participants in nuclear testing could get $75,000. Uranium miners, millers, and ore transporters in 11 states west of the Mississippi River could get $100,000.

Among downwinders, eligible cancers included blood cancers (leukemias with the exception of chronic lymphocytic leukemia, multiple myeloma, and non-Hodgkin’s lymphomas) and a long list of solid organ cancers such as thyroid, breast, stomach, brain, lung, colon, and liver cancers.

“When it comes to blood-related cancers, we do see leukemias, lymphomas, and multiple myeloma, but these cancers were more likely to occur sooner after fallout exposure,” said Laura Shaw, MD, principal investigator who oversees the radiation exposure screening program at the University of Nevada, Las Vegas. “At this point, we see more pancreatic, thyroid, lung, stomach, bladder, and breast cancer.”

The compensation program had major limitations, critics said. “It left out a lot of communities that were exposed,” said Lilly Adams, senior outreach coordinator with the Union of Concerned Scientists (UCS), which supports expanding the program. A national nonprofit organization, UCS was founded more than 50 years ago by scientists and students at the Massachusetts Institute of Technology.

“You have this pretty small amount of one-time compensation, and that’s it,” Adams said in an interview. “You can’t get reimbursed for medical costs or lost wages.” Still, “as flawed as the program is, it’s really valuable for the people who are eligible,” she noted.
 

Now Congress Is Divided on Next Steps

Some lawmakers have recognized the need to do more for those who developed cancer that’s potentially linked to radiation exposure. As the June 2024 expiration of the Radiation Exposure Compensation Act loomed, Democrats and Republicans in Congress worked together to extend and expand the program.

They introduced a bill for higher compensation — $100,000 per person — and the widening of covered downwinder areas to all of Arizona, Nevada, and Utah (which had only been partially covered), along with all of Colorado, Idaho, New Mexico, Montana, and Guam. Under the legislation, the program also would expand to cover some uranium workers who were on the job after 1971 and residents exposed to nuclear waste in Kentucky, Missouri, and Tennessee.

In March, the new legislation easily passed the US Senate by a vote of 69-30, with support from both political parties — but the Republican-led House hasn’t taken it up. As a result, the Radiation Exposure Compensation Act expired in June, and no one can submit new applications for compensation.

A spokesman for House Speaker Mike Johnson told Missouri Independent “unfortunately, the current Senate bill is estimated to cost $50-$60 billion in new mandatory spending with no offsets and was supported by only 20 of 49 Republicans in the Senate.”

Adams rejected these arguments. “The government spends literally trillions of dollars on our nuclear weapons. Whether or not you support that spending, the human cost of building those weapons should be factored in,” she said. She added that she hopes the House will act by the end of the year to pass the bill, but that’s uncertain.
 

As Compensation Is On Hold, Medical Screening Continues

A major benefit is still available for downwinders and uranium workers: Free medical screening and referrals for medical treatment. The Radiation Exposure Screening and Education Program’s funding has not been affected by the congressional impasse, so screenings are continuing for eligible people exposed to radiation.

Radiation exposure clinics offer screening in Arizona, Colorado, Nevada, New Mexico, and Utah, and health providers can get funding to offer screening in other affected states.

In Nevada, “we hold screening clinics throughout the state: Caliente, Ely, and Winnemucca. Also, in Reno and Las Vegas, which are not in designated downwind areas, but many downwinders have migrated there,” said Shaw in an interview. Among downwinders, “our youngest patients are in their 60s and range up to a few in their 90s,” she said.

Patients fill out questionnaires that ask about their medical problems, family history, and medications. “Ely patients in particular seem to have extensive family histories of cancer, and this may be due to their location directly downwind of the Nevada Test Site,” Shaw said. (Ely is a remote town in central eastern Nevada near the Utah border.)

The screenings cover both cancer and noncancer conditions. Shaw said clinicians often diagnose problems other than the covered cancers — new cases of atrial fibrillation, diabetes, and hypertension. “We see a ton of prostate and skin cancer” but don’t make patients eligible for the compensation program because they’re not covered, she said.

Even as compensation is on hold, doctors can get the word out that screenings are still available, Shaw said. “We continue to get contacted by individuals who in these communities who have never heard of this program, even though we’ve been holding clinics since 2005,” Shaw said. “Despite outreach activities and advertising through newspapers and radio, we find the most successful method of reaching these patients is through word of mouth — either from other patients or their doctors. That is why we feel it is so important to reach other physicians as well.”
 

Affected Patients Don’t Just Live in the West

On the outreach front, clinicians in states outside of the western US region can be helpful, too. Shaw urged oncologists nationwide to ask older patients where they lived in the 1950s and 1960s. “Did they live in Nevada, Arizona, Utah, and other Western states that are downwind? They may qualify for needed services and future compensation.”

With regard to compensation, she noted that applicants need to prove that they lived in affected areas many decades ago. And, of course, they must prove that they’ve had cancer. Locating residency records “has often been an enormous challenge.” Old utility bills, pay stubs, and high school annuals can be helpful, “but these records tend to disappear. People and their families throw stuff away.”

Even proving a cancer diagnosis can be a challenge because records can be missing. In Nevada, the law says clinicians only need to keep medical records for 5 years, Shaw said. “Imaging and pathology reports are destroyed. Patients that have been diagnosed with cancer can’t prove it.”

Shaw said she hopes oncologists will offer these messages to patients: “Be an advocate for your own health and keep copies of your own records. Discuss your diagnosis with your family and contact a cancer registry if you are diagnosed with cancer.”
 

A version of this article appeared on Medscape.com.

For more than three decades, the federal government sought to make amends to countless Americans who developed cancer after being exposed to radiation from nuclear testing in the Southwest or while working in the uranium mining industry.

As of 2022, more than 40,000 patients with cancer successfully applied for $2.6 billion in compensation. Recipients included “downwinders” who were eligible for $50,000 each if they lived in certain areas of Nevada, Utah, and Arizona during specified nuclear testing periods and developed a covered form of cancer.

In June 2024, however, the Radiation Exposure Compensation Program expired amid infighting among Republicans in Congress over whether to expand it. For now, no one can make a claim, even though many downwinders are still alive and continue to be diagnosed with covered cancers decades after they were exposed in the 1940s, 1950s, and 1960s.

There’s a glimmer of good news. The federal government continues to support free medical screenings for eligible people, including certain downwinders and uranium workers. Meanwhile, there are still important roles for clinicians across the country to play as politicians figure out what — if anything — to do next regarding those exposed to radiation.

“We are still here. We can still screen people,” Zachary Davis, program director for the Radiation Exposure Screening and Education Program, The University of New Mexico, in Albuquerque, New Mexico, said in an interview.
 

Still-Unfolding Legacy of Radiation Exposure

No one knew just how far radiation would spread when the first nuclear bomb was tested in New Mexico in July 1945. Would it cover the state? The entire Southwest? The whole nation?

It also wasn’t clear how radiation would affect people’s health. “There was an awareness that some cancers were caused by radiation, but there wasn’t a cohesive understanding of what the problem was,” Joseph Shonka, PhD, a health physicist who studies radiation exposure and has worked for decades in nuclear engineering, said in an interview.

Now, nearly eight decades later, scientists are still figuring out the full extent of radioactive fallout from nuclear testing. Just last year, a study suggested that radiation from 94 nuclear weapon tests in the Southwest from 1945 to 1962 reached 46 states along with Canada and Mexico.

Activists believe the tests triggered untold number of cancer cases in residents who were exposed in downwind areas:

“My brother died of stomach cancer; my mom died of bone cancer. One of my sisters is surviving brain tumors, and the other one is surviving thyroid cancer,” one New Mexico man recently told ABC-TV’s “Nightline.”

In Idaho, a downwinder advocate told Idaho Capital Sun that everyone who attended a reception for her newly married parents in 1952 — just weeks after a nuclear test — developed cancer or “weird medical complications.” That included her parents, who both had cancer. Her two older brothers, born in 1953 and 1955, also developed cancer, and she’s tracked many other cases in the small town of Emmett.

In Utah, another downwinder advocate told Utah News Dispatch that cancer was common in Salt Lake City neighborhood, where she grew up, which was exposed to fallout. She developed thyroid cancer, her younger sister developed stomach cancer, and an older sister died of lupus, which is connected to radiation exposure. But Salt Lake City isn’t in one of the regions of Utah covered by the federal compensation program, so the advocate can’t get a $50,000 payment.

Downwinders who lived in New Mexico, Idaho, and the Salt Lake City area of Utah are not covered by the federal compensation program. That means none of these people or their descendants are eligible for payments — yet.
 

Decades After Nuclear Testing, the Government Responds

In 1990, Congress passed the Radiation Exposure Compensation Act, which allowed compensation to people with cancer at several levels. It was later expanded. Downwinders — including those who’ve moved elsewhere over the years — were eligible for $50,000. Onsite participants in nuclear testing could get $75,000. Uranium miners, millers, and ore transporters in 11 states west of the Mississippi River could get $100,000.

Among downwinders, eligible cancers included blood cancers (leukemias with the exception of chronic lymphocytic leukemia, multiple myeloma, and non-Hodgkin’s lymphomas) and a long list of solid organ cancers such as thyroid, breast, stomach, brain, lung, colon, and liver cancers.

“When it comes to blood-related cancers, we do see leukemias, lymphomas, and multiple myeloma, but these cancers were more likely to occur sooner after fallout exposure,” said Laura Shaw, MD, principal investigator who oversees the radiation exposure screening program at the University of Nevada, Las Vegas. “At this point, we see more pancreatic, thyroid, lung, stomach, bladder, and breast cancer.”

The compensation program had major limitations, critics said. “It left out a lot of communities that were exposed,” said Lilly Adams, senior outreach coordinator with the Union of Concerned Scientists (UCS), which supports expanding the program. A national nonprofit organization, UCS was founded more than 50 years ago by scientists and students at the Massachusetts Institute of Technology.

“You have this pretty small amount of one-time compensation, and that’s it,” Adams said in an interview. “You can’t get reimbursed for medical costs or lost wages.” Still, “as flawed as the program is, it’s really valuable for the people who are eligible,” she noted.
 

Now Congress Is Divided on Next Steps

Some lawmakers have recognized the need to do more for those who developed cancer that’s potentially linked to radiation exposure. As the June 2024 expiration of the Radiation Exposure Compensation Act loomed, Democrats and Republicans in Congress worked together to extend and expand the program.

They introduced a bill for higher compensation — $100,000 per person — and the widening of covered downwinder areas to all of Arizona, Nevada, and Utah (which had only been partially covered), along with all of Colorado, Idaho, New Mexico, Montana, and Guam. Under the legislation, the program also would expand to cover some uranium workers who were on the job after 1971 and residents exposed to nuclear waste in Kentucky, Missouri, and Tennessee.

In March, the new legislation easily passed the US Senate by a vote of 69-30, with support from both political parties — but the Republican-led House hasn’t taken it up. As a result, the Radiation Exposure Compensation Act expired in June, and no one can submit new applications for compensation.

A spokesman for House Speaker Mike Johnson told Missouri Independent “unfortunately, the current Senate bill is estimated to cost $50-$60 billion in new mandatory spending with no offsets and was supported by only 20 of 49 Republicans in the Senate.”

Adams rejected these arguments. “The government spends literally trillions of dollars on our nuclear weapons. Whether or not you support that spending, the human cost of building those weapons should be factored in,” she said. She added that she hopes the House will act by the end of the year to pass the bill, but that’s uncertain.
 

As Compensation Is On Hold, Medical Screening Continues

A major benefit is still available for downwinders and uranium workers: Free medical screening and referrals for medical treatment. The Radiation Exposure Screening and Education Program’s funding has not been affected by the congressional impasse, so screenings are continuing for eligible people exposed to radiation.

Radiation exposure clinics offer screening in Arizona, Colorado, Nevada, New Mexico, and Utah, and health providers can get funding to offer screening in other affected states.

In Nevada, “we hold screening clinics throughout the state: Caliente, Ely, and Winnemucca. Also, in Reno and Las Vegas, which are not in designated downwind areas, but many downwinders have migrated there,” said Shaw in an interview. Among downwinders, “our youngest patients are in their 60s and range up to a few in their 90s,” she said.

Patients fill out questionnaires that ask about their medical problems, family history, and medications. “Ely patients in particular seem to have extensive family histories of cancer, and this may be due to their location directly downwind of the Nevada Test Site,” Shaw said. (Ely is a remote town in central eastern Nevada near the Utah border.)

The screenings cover both cancer and noncancer conditions. Shaw said clinicians often diagnose problems other than the covered cancers — new cases of atrial fibrillation, diabetes, and hypertension. “We see a ton of prostate and skin cancer” but don’t make patients eligible for the compensation program because they’re not covered, she said.

Even as compensation is on hold, doctors can get the word out that screenings are still available, Shaw said. “We continue to get contacted by individuals who in these communities who have never heard of this program, even though we’ve been holding clinics since 2005,” Shaw said. “Despite outreach activities and advertising through newspapers and radio, we find the most successful method of reaching these patients is through word of mouth — either from other patients or their doctors. That is why we feel it is so important to reach other physicians as well.”
 

Affected Patients Don’t Just Live in the West

On the outreach front, clinicians in states outside of the western US region can be helpful, too. Shaw urged oncologists nationwide to ask older patients where they lived in the 1950s and 1960s. “Did they live in Nevada, Arizona, Utah, and other Western states that are downwind? They may qualify for needed services and future compensation.”

With regard to compensation, she noted that applicants need to prove that they lived in affected areas many decades ago. And, of course, they must prove that they’ve had cancer. Locating residency records “has often been an enormous challenge.” Old utility bills, pay stubs, and high school annuals can be helpful, “but these records tend to disappear. People and their families throw stuff away.”

Even proving a cancer diagnosis can be a challenge because records can be missing. In Nevada, the law says clinicians only need to keep medical records for 5 years, Shaw said. “Imaging and pathology reports are destroyed. Patients that have been diagnosed with cancer can’t prove it.”

Shaw said she hopes oncologists will offer these messages to patients: “Be an advocate for your own health and keep copies of your own records. Discuss your diagnosis with your family and contact a cancer registry if you are diagnosed with cancer.”
 

A version of this article appeared on Medscape.com.

Adding a second checkpoint inhibitor to chemotherapy improves outcomes among patients with non–small cell lung cancer (NSCLC) who have STK11 and/or KEAP1 mutations, according to the authors of a new paper.

These findings, drawn from a post hoc analysis of phase 3 data, are backed up by cell line and mouse data revealing clear mechanisms of efficacy, making the collective evidence compelling enough to reshape clinical practice, reported lead author Ferdinandos Skoulidis, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston.

“Although STK11 and KEAP1 mutations are associated with limited benefit from PD-1 or PD-L1 [PD-(L)1] inhibition, the association between these mutations and benefit from combinations of PD-(L)1 inhibitors with chemotherapy is not yet as well established,” the investigators wrote in Nature.

Skoulidis and colleagues conducted the subgroup analysis of POSEIDON trial data and characterized underlying biologic mechanisms using mouse models to address this knowledge gap.
 

What Were the Original Findings of POSEIDON?

The POSEIDON trial involved 1013 patients with metastatic NSCLC. Treatment arms included standard chemotherapy alone, chemotherapy plus programmed death ligand 1 (PD-L1) inhibitor durvalumab, and chemotherapy plus durvalumab and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor tremelimumab.

Adding durvalumab to chemotherapy significantly improved median progression-free survival (PFS) but not median overall survival (OS), while dual checkpoint blockade boosted both PFS and OS.

These findings provided support for the dual approach in the first-line setting, but not preferentially so. Experts called for more long-term data, questioned the survival benefit in terms of the increased toxicity, and noted the lack of biomarkers for patient selection.
 

What Did Post Hoc Analysis Highlight About POSEIDON?

The present analysis aimed to validate two actionable biomarkers.

“We and others have previously observed that alterations in STK11 and KEAP1 can promote an immunosuppressive tumor microenvironment and together might be responsible for half or more of the primary resistance to PD-(L)1 inhibition among patients with nsNSCLC when given as monotherapy,” Skoulidis and colleagues wrote.

From the original 1013 patients, 612 had non-squamous NSCLC and were evaluable for mutations. Among them, 87 had STK11 mutations and 37 had KEAP1 mutations.

As anticipated, patients in the STK11/KEAP1 subgroup saw little to no benefit from adding durvalumab to chemotherapy, but adding tremelimumab on top yielded notable improvement.

This was first observed in the objective response rate, which was 42.9% with dual checkpoint blockade plus chemotherapy vs 30.2% with single checkpoint blockade plus chemotherapy and 28% for chemotherapy alone. Durations of response improved in kind.

Survival outcomes also trended toward improvement in the dual checkpoint arm, which had a median OS of 15.8 months vs 7.3 months for durvalumab plus chemotherapy (hazard ratio [HR], 0.64; 95% CI, 0.40-1.04) and 10.5 months for chemotherapy alone (HR, 0.50; 95% CI, 0.29-0.87). PFS showed similar trends.
 

How Do Findings Relate to Previous NSCLC Subgroup Research?

Skoulidis and colleagues noted that their findings align with those of the CheckMate 9LA trial, which showed that patients with STK11 and/or KEAP1 mutations had better outcomes with dual checkpoint blockade plus chemotherapy than with chemotherapy alone.

“These data support the hypothesis that CTLA-4 inhibition can mitigate the resistance to chemotherapy plus PD-(L)1 inhibition observed in patients who have STK11 and/or KEAP1 mutations and suggest that this group of patients derives greater benefit from CTLA-4 inhibition than do patients who lack either alteration,” Skoulidis and colleagues wrote.

Grace Dy, MD, professor of oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center, Buffalo, New York, noted that in the present analysis, PD-L1 expression status did not predict outcomes; however, patients with STK11 and/or KEAP1 mutations typically have low or negative PD-L1 expression, which has been linked with better responses to CTLA-4 inhibition in multiple trials.

“In the CheckMate 227 and CheckMate 9LA studies, we have seen that patients with PD-L1–negative tumors appear to derive greater and more durable long-term overall survival benefit from dual immune checkpoint blockade compared to patients receiving anti-PD1-based therapy alone,” Dy said in a written comment. “While we take the necessary caveats on cross-trial comparisons, the same survival trend favoring CTLA-4-based immune checkpoint blockade is seen compared to the tail of the survival curves observed in PD-L1–negative patients enrolled in the KEYNOTE studies (KEYNOTE-189, KEYNOTE-407).”

Detecting improvements in survival within PD-L1 patients “may not be readily apparent until later when looking at the tail of the survival curves,” she added.
 

What Mechanisms of Action Explain Relative Benefits of Dual Checkpoint Blockade?

To elucidate underlying mechanisms of action, Skoulidis and colleagues conducted a series of experiments involving cell lines and mouse models of Stk11- and Keap1-deficient NSCLC.

“For us, it was critical to provide mechanistic support for the observed clinical benefit in POSEIDON, especially since this is based on a retrospective subgroup analysis,” Skoulidis said in an interview.

Their efforts revealed a strong link between the mutations and resistance to PD-(L)1 inhibition.

Inactivation of Stk11 and Keap1 promoted an immunosuppressive tumor microenvironment, marked by increased infiltration of suppressive myeloid cells and a reduction in CD8+ effector T cells. This immune imbalance contributed to evasion of immune destruction and limited the efficacy of programmed cell death protein 1 (PD-1) blockade.

Dual checkpoint blockade reprogrammed the immune microenvironment, leading to increased activation of CD4+ T helper (Th) cells, specifically the Th1 subtype, while inducing tumoricidal changes in myeloid cells. Consequently, antitumor responses improved, resulting in tumor regression and prolonged survival, compared with PD-1 monotherapy.

“Addition of CTLA-4 [inhibition] turns the two cardinal components of the suppressive microenvironment of these tumors on its head, and that’s why we believe we are observing this clinical benefit,” Skoulidis said. “This is not a mere association…but also based on very solid mechanistic data across a multitude of different models.”
 

Are Data Sufficient to Shift to First-Line Dual Checkpoint Blockade?

“Our work strengthens the available evidence that this regimen — and chemoimmunotherapy more broadly, with dual immune checkpoint blockade — constitutes a preferred approach for these patients,” Skoulidis said. “I personally, and I think physicians within MD Anderson, as well as a lot of physicians that I talk to, are already using — based on these data — the POSEIDON regimen, as well as, more broadly, chemoimmunotherapy with dual immune checkpoint for patients with these alterations.”

This view, however, remains contested by some oncologists.

Lei Deng, MD, assistant professor in the Division of Hematology and Oncology at the University of Washington, Fred Hutchinson Cancer Center, Seattle, called the new data “intriguing” and “hypothesis-generating,” but stopped short of supporting preferential first-line use.

“This study is a post hoc analysis, so you don’t have a lot of patients,” Deng said. “It is still not strong enough or definitive enough to make it standard of care to use dual checkpoint blockade for [patients with STK11 and/or KEAP1 mutations].”

The cell line and mouse data help explain biologic mechanisms of efficacy, he said, but these findings do not obviate toxicity concerns.

“You are adding one more agent, and this agent is more toxic than single checkpoint blockade,” Deng said. “So, if you weigh the risk, it is known, [but] the benefit is suggestive. I am not sure if the risk-benefit ratio would argue for routine implementation of this regimen yet.”

On the other hand, he noted, the combination is the US Food and Drug Administration–approved in this setting, so “it is not wrong to use it.”

Jyoti Malhotra, MD, director of thoracic medical oncology at City of Hope Orange County in Irvine, California, had a similar take.

“The clinical data presented so far is exploratory and limited by the small sample size,” Malhotra said in a written comment. “Data from an ongoing phase 3 trial (TRITON) is awaited before dual checkpoint blockade becomes the standard of care in this setting.”

Hossein Borghaei, DO, chief of the Division of Thoracic Medical Oncology at Fox Chase Cancer Center, Philadelphia, was also unequivocal when asked if dual checkpoint blockade with chemotherapy should be considered the preferred first-line treatment option in patients with STK11 and/or KEAP1 mutations.

“No,” he said in a written comment. “The data and the hypothesis are very strong, but it is all based on retrospective clinical data, cell line data, and mouse models. We need a randomized study to test the hypothesis.”

Incidentally, Borghaei is on the steering committee for the TRITON trial. He shared this potential conflict of interest before praising Skoulidis and colleagues for their efforts, noting that the present findings underscore the broader importance of widespread tumor profiling and access to resultant data.

“This is a beautiful story that has developed over the last few years based on the research by the group from MD Anderson who has reported the current Nature article,” he said. “This highlights the possible utility of collecting sequencing data on [all] patients’ tumors. These sorts of understandings and new ideas could arise only if there is access to this information.”

The study was supported by AstraZeneca, the National Cancer Institute, the Gunnigar Fund, and others. The investigators disclosed additional relationships with Novartis, Merck, Amgen, and others. Deng disclosed relationships with Merck, BridgeBio, MJH Life Sciences, and others. Dy disclosed relationships with Eli Lilly and Company, Janssen Pharmaceuticals, Meru, and others. Malhotra has previously served as a consultant for AstraZeneca. Borghaei has served as a consultant for AstraZeneca and is on the steering committee for the TRITON trial.
 

A version of this article appeared on Medscape.com.

Adding a second checkpoint inhibitor to chemotherapy improves outcomes among patients with non–small cell lung cancer (NSCLC) who have STK11 and/or KEAP1 mutations, according to the authors of a new paper.

These findings, drawn from a post hoc analysis of phase 3 data, are backed up by cell line and mouse data revealing clear mechanisms of efficacy, making the collective evidence compelling enough to reshape clinical practice, reported lead author Ferdinandos Skoulidis, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston.

“Although STK11 and KEAP1 mutations are associated with limited benefit from PD-1 or PD-L1 [PD-(L)1] inhibition, the association between these mutations and benefit from combinations of PD-(L)1 inhibitors with chemotherapy is not yet as well established,” the investigators wrote in Nature.

Skoulidis and colleagues conducted the subgroup analysis of POSEIDON trial data and characterized underlying biologic mechanisms using mouse models to address this knowledge gap.
 

What Were the Original Findings of POSEIDON?

The POSEIDON trial involved 1013 patients with metastatic NSCLC. Treatment arms included standard chemotherapy alone, chemotherapy plus programmed death ligand 1 (PD-L1) inhibitor durvalumab, and chemotherapy plus durvalumab and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor tremelimumab.

Adding durvalumab to chemotherapy significantly improved median progression-free survival (PFS) but not median overall survival (OS), while dual checkpoint blockade boosted both PFS and OS.

These findings provided support for the dual approach in the first-line setting, but not preferentially so. Experts called for more long-term data, questioned the survival benefit in terms of the increased toxicity, and noted the lack of biomarkers for patient selection.
 

What Did Post Hoc Analysis Highlight About POSEIDON?

The present analysis aimed to validate two actionable biomarkers.

“We and others have previously observed that alterations in STK11 and KEAP1 can promote an immunosuppressive tumor microenvironment and together might be responsible for half or more of the primary resistance to PD-(L)1 inhibition among patients with nsNSCLC when given as monotherapy,” Skoulidis and colleagues wrote.

From the original 1013 patients, 612 had non-squamous NSCLC and were evaluable for mutations. Among them, 87 had STK11 mutations and 37 had KEAP1 mutations.

As anticipated, patients in the STK11/KEAP1 subgroup saw little to no benefit from adding durvalumab to chemotherapy, but adding tremelimumab on top yielded notable improvement.

This was first observed in the objective response rate, which was 42.9% with dual checkpoint blockade plus chemotherapy vs 30.2% with single checkpoint blockade plus chemotherapy and 28% for chemotherapy alone. Durations of response improved in kind.

Survival outcomes also trended toward improvement in the dual checkpoint arm, which had a median OS of 15.8 months vs 7.3 months for durvalumab plus chemotherapy (hazard ratio [HR], 0.64; 95% CI, 0.40-1.04) and 10.5 months for chemotherapy alone (HR, 0.50; 95% CI, 0.29-0.87). PFS showed similar trends.
 

How Do Findings Relate to Previous NSCLC Subgroup Research?

Skoulidis and colleagues noted that their findings align with those of the CheckMate 9LA trial, which showed that patients with STK11 and/or KEAP1 mutations had better outcomes with dual checkpoint blockade plus chemotherapy than with chemotherapy alone.

“These data support the hypothesis that CTLA-4 inhibition can mitigate the resistance to chemotherapy plus PD-(L)1 inhibition observed in patients who have STK11 and/or KEAP1 mutations and suggest that this group of patients derives greater benefit from CTLA-4 inhibition than do patients who lack either alteration,” Skoulidis and colleagues wrote.

Grace Dy, MD, professor of oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center, Buffalo, New York, noted that in the present analysis, PD-L1 expression status did not predict outcomes; however, patients with STK11 and/or KEAP1 mutations typically have low or negative PD-L1 expression, which has been linked with better responses to CTLA-4 inhibition in multiple trials.

“In the CheckMate 227 and CheckMate 9LA studies, we have seen that patients with PD-L1–negative tumors appear to derive greater and more durable long-term overall survival benefit from dual immune checkpoint blockade compared to patients receiving anti-PD1-based therapy alone,” Dy said in a written comment. “While we take the necessary caveats on cross-trial comparisons, the same survival trend favoring CTLA-4-based immune checkpoint blockade is seen compared to the tail of the survival curves observed in PD-L1–negative patients enrolled in the KEYNOTE studies (KEYNOTE-189, KEYNOTE-407).”

Detecting improvements in survival within PD-L1 patients “may not be readily apparent until later when looking at the tail of the survival curves,” she added.
 

What Mechanisms of Action Explain Relative Benefits of Dual Checkpoint Blockade?

To elucidate underlying mechanisms of action, Skoulidis and colleagues conducted a series of experiments involving cell lines and mouse models of Stk11- and Keap1-deficient NSCLC.

“For us, it was critical to provide mechanistic support for the observed clinical benefit in POSEIDON, especially since this is based on a retrospective subgroup analysis,” Skoulidis said in an interview.

Their efforts revealed a strong link between the mutations and resistance to PD-(L)1 inhibition.

Inactivation of Stk11 and Keap1 promoted an immunosuppressive tumor microenvironment, marked by increased infiltration of suppressive myeloid cells and a reduction in CD8+ effector T cells. This immune imbalance contributed to evasion of immune destruction and limited the efficacy of programmed cell death protein 1 (PD-1) blockade.

Dual checkpoint blockade reprogrammed the immune microenvironment, leading to increased activation of CD4+ T helper (Th) cells, specifically the Th1 subtype, while inducing tumoricidal changes in myeloid cells. Consequently, antitumor responses improved, resulting in tumor regression and prolonged survival, compared with PD-1 monotherapy.

“Addition of CTLA-4 [inhibition] turns the two cardinal components of the suppressive microenvironment of these tumors on its head, and that’s why we believe we are observing this clinical benefit,” Skoulidis said. “This is not a mere association…but also based on very solid mechanistic data across a multitude of different models.”
 

Are Data Sufficient to Shift to First-Line Dual Checkpoint Blockade?

“Our work strengthens the available evidence that this regimen — and chemoimmunotherapy more broadly, with dual immune checkpoint blockade — constitutes a preferred approach for these patients,” Skoulidis said. “I personally, and I think physicians within MD Anderson, as well as a lot of physicians that I talk to, are already using — based on these data — the POSEIDON regimen, as well as, more broadly, chemoimmunotherapy with dual immune checkpoint for patients with these alterations.”

This view, however, remains contested by some oncologists.

Lei Deng, MD, assistant professor in the Division of Hematology and Oncology at the University of Washington, Fred Hutchinson Cancer Center, Seattle, called the new data “intriguing” and “hypothesis-generating,” but stopped short of supporting preferential first-line use.

“This study is a post hoc analysis, so you don’t have a lot of patients,” Deng said. “It is still not strong enough or definitive enough to make it standard of care to use dual checkpoint blockade for [patients with STK11 and/or KEAP1 mutations].”

The cell line and mouse data help explain biologic mechanisms of efficacy, he said, but these findings do not obviate toxicity concerns.

“You are adding one more agent, and this agent is more toxic than single checkpoint blockade,” Deng said. “So, if you weigh the risk, it is known, [but] the benefit is suggestive. I am not sure if the risk-benefit ratio would argue for routine implementation of this regimen yet.”

On the other hand, he noted, the combination is the US Food and Drug Administration–approved in this setting, so “it is not wrong to use it.”

Jyoti Malhotra, MD, director of thoracic medical oncology at City of Hope Orange County in Irvine, California, had a similar take.

“The clinical data presented so far is exploratory and limited by the small sample size,” Malhotra said in a written comment. “Data from an ongoing phase 3 trial (TRITON) is awaited before dual checkpoint blockade becomes the standard of care in this setting.”

Hossein Borghaei, DO, chief of the Division of Thoracic Medical Oncology at Fox Chase Cancer Center, Philadelphia, was also unequivocal when asked if dual checkpoint blockade with chemotherapy should be considered the preferred first-line treatment option in patients with STK11 and/or KEAP1 mutations.

“No,” he said in a written comment. “The data and the hypothesis are very strong, but it is all based on retrospective clinical data, cell line data, and mouse models. We need a randomized study to test the hypothesis.”

Incidentally, Borghaei is on the steering committee for the TRITON trial. He shared this potential conflict of interest before praising Skoulidis and colleagues for their efforts, noting that the present findings underscore the broader importance of widespread tumor profiling and access to resultant data.

“This is a beautiful story that has developed over the last few years based on the research by the group from MD Anderson who has reported the current Nature article,” he said. “This highlights the possible utility of collecting sequencing data on [all] patients’ tumors. These sorts of understandings and new ideas could arise only if there is access to this information.”

The study was supported by AstraZeneca, the National Cancer Institute, the Gunnigar Fund, and others. The investigators disclosed additional relationships with Novartis, Merck, Amgen, and others. Deng disclosed relationships with Merck, BridgeBio, MJH Life Sciences, and others. Dy disclosed relationships with Eli Lilly and Company, Janssen Pharmaceuticals, Meru, and others. Malhotra has previously served as a consultant for AstraZeneca. Borghaei has served as a consultant for AstraZeneca and is on the steering committee for the TRITON trial.
 

A version of this article appeared on Medscape.com.

Adding a second checkpoint inhibitor to chemotherapy improves outcomes among patients with non–small cell lung cancer (NSCLC) who have STK11 and/or KEAP1 mutations, according to the authors of a new paper.

These findings, drawn from a post hoc analysis of phase 3 data, are backed up by cell line and mouse data revealing clear mechanisms of efficacy, making the collective evidence compelling enough to reshape clinical practice, reported lead author Ferdinandos Skoulidis, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston.

“Although STK11 and KEAP1 mutations are associated with limited benefit from PD-1 or PD-L1 [PD-(L)1] inhibition, the association between these mutations and benefit from combinations of PD-(L)1 inhibitors with chemotherapy is not yet as well established,” the investigators wrote in Nature.

Skoulidis and colleagues conducted the subgroup analysis of POSEIDON trial data and characterized underlying biologic mechanisms using mouse models to address this knowledge gap.
 

What Were the Original Findings of POSEIDON?

The POSEIDON trial involved 1013 patients with metastatic NSCLC. Treatment arms included standard chemotherapy alone, chemotherapy plus programmed death ligand 1 (PD-L1) inhibitor durvalumab, and chemotherapy plus durvalumab and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor tremelimumab.

Adding durvalumab to chemotherapy significantly improved median progression-free survival (PFS) but not median overall survival (OS), while dual checkpoint blockade boosted both PFS and OS.

These findings provided support for the dual approach in the first-line setting, but not preferentially so. Experts called for more long-term data, questioned the survival benefit in terms of the increased toxicity, and noted the lack of biomarkers for patient selection.
 

What Did Post Hoc Analysis Highlight About POSEIDON?

The present analysis aimed to validate two actionable biomarkers.

“We and others have previously observed that alterations in STK11 and KEAP1 can promote an immunosuppressive tumor microenvironment and together might be responsible for half or more of the primary resistance to PD-(L)1 inhibition among patients with nsNSCLC when given as monotherapy,” Skoulidis and colleagues wrote.

From the original 1013 patients, 612 had non-squamous NSCLC and were evaluable for mutations. Among them, 87 had STK11 mutations and 37 had KEAP1 mutations.

As anticipated, patients in the STK11/KEAP1 subgroup saw little to no benefit from adding durvalumab to chemotherapy, but adding tremelimumab on top yielded notable improvement.

This was first observed in the objective response rate, which was 42.9% with dual checkpoint blockade plus chemotherapy vs 30.2% with single checkpoint blockade plus chemotherapy and 28% for chemotherapy alone. Durations of response improved in kind.

Survival outcomes also trended toward improvement in the dual checkpoint arm, which had a median OS of 15.8 months vs 7.3 months for durvalumab plus chemotherapy (hazard ratio [HR], 0.64; 95% CI, 0.40-1.04) and 10.5 months for chemotherapy alone (HR, 0.50; 95% CI, 0.29-0.87). PFS showed similar trends.
 

How Do Findings Relate to Previous NSCLC Subgroup Research?

Skoulidis and colleagues noted that their findings align with those of the CheckMate 9LA trial, which showed that patients with STK11 and/or KEAP1 mutations had better outcomes with dual checkpoint blockade plus chemotherapy than with chemotherapy alone.

“These data support the hypothesis that CTLA-4 inhibition can mitigate the resistance to chemotherapy plus PD-(L)1 inhibition observed in patients who have STK11 and/or KEAP1 mutations and suggest that this group of patients derives greater benefit from CTLA-4 inhibition than do patients who lack either alteration,” Skoulidis and colleagues wrote.

Grace Dy, MD, professor of oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center, Buffalo, New York, noted that in the present analysis, PD-L1 expression status did not predict outcomes; however, patients with STK11 and/or KEAP1 mutations typically have low or negative PD-L1 expression, which has been linked with better responses to CTLA-4 inhibition in multiple trials.

“In the CheckMate 227 and CheckMate 9LA studies, we have seen that patients with PD-L1–negative tumors appear to derive greater and more durable long-term overall survival benefit from dual immune checkpoint blockade compared to patients receiving anti-PD1-based therapy alone,” Dy said in a written comment. “While we take the necessary caveats on cross-trial comparisons, the same survival trend favoring CTLA-4-based immune checkpoint blockade is seen compared to the tail of the survival curves observed in PD-L1–negative patients enrolled in the KEYNOTE studies (KEYNOTE-189, KEYNOTE-407).”

Detecting improvements in survival within PD-L1 patients “may not be readily apparent until later when looking at the tail of the survival curves,” she added.
 

What Mechanisms of Action Explain Relative Benefits of Dual Checkpoint Blockade?

To elucidate underlying mechanisms of action, Skoulidis and colleagues conducted a series of experiments involving cell lines and mouse models of Stk11- and Keap1-deficient NSCLC.

“For us, it was critical to provide mechanistic support for the observed clinical benefit in POSEIDON, especially since this is based on a retrospective subgroup analysis,” Skoulidis said in an interview.

Their efforts revealed a strong link between the mutations and resistance to PD-(L)1 inhibition.

Inactivation of Stk11 and Keap1 promoted an immunosuppressive tumor microenvironment, marked by increased infiltration of suppressive myeloid cells and a reduction in CD8+ effector T cells. This immune imbalance contributed to evasion of immune destruction and limited the efficacy of programmed cell death protein 1 (PD-1) blockade.

Dual checkpoint blockade reprogrammed the immune microenvironment, leading to increased activation of CD4+ T helper (Th) cells, specifically the Th1 subtype, while inducing tumoricidal changes in myeloid cells. Consequently, antitumor responses improved, resulting in tumor regression and prolonged survival, compared with PD-1 monotherapy.

“Addition of CTLA-4 [inhibition] turns the two cardinal components of the suppressive microenvironment of these tumors on its head, and that’s why we believe we are observing this clinical benefit,” Skoulidis said. “This is not a mere association…but also based on very solid mechanistic data across a multitude of different models.”
 

Are Data Sufficient to Shift to First-Line Dual Checkpoint Blockade?

“Our work strengthens the available evidence that this regimen — and chemoimmunotherapy more broadly, with dual immune checkpoint blockade — constitutes a preferred approach for these patients,” Skoulidis said. “I personally, and I think physicians within MD Anderson, as well as a lot of physicians that I talk to, are already using — based on these data — the POSEIDON regimen, as well as, more broadly, chemoimmunotherapy with dual immune checkpoint for patients with these alterations.”

This view, however, remains contested by some oncologists.

Lei Deng, MD, assistant professor in the Division of Hematology and Oncology at the University of Washington, Fred Hutchinson Cancer Center, Seattle, called the new data “intriguing” and “hypothesis-generating,” but stopped short of supporting preferential first-line use.

“This study is a post hoc analysis, so you don’t have a lot of patients,” Deng said. “It is still not strong enough or definitive enough to make it standard of care to use dual checkpoint blockade for [patients with STK11 and/or KEAP1 mutations].”

The cell line and mouse data help explain biologic mechanisms of efficacy, he said, but these findings do not obviate toxicity concerns.

“You are adding one more agent, and this agent is more toxic than single checkpoint blockade,” Deng said. “So, if you weigh the risk, it is known, [but] the benefit is suggestive. I am not sure if the risk-benefit ratio would argue for routine implementation of this regimen yet.”

On the other hand, he noted, the combination is the US Food and Drug Administration–approved in this setting, so “it is not wrong to use it.”

Jyoti Malhotra, MD, director of thoracic medical oncology at City of Hope Orange County in Irvine, California, had a similar take.

“The clinical data presented so far is exploratory and limited by the small sample size,” Malhotra said in a written comment. “Data from an ongoing phase 3 trial (TRITON) is awaited before dual checkpoint blockade becomes the standard of care in this setting.”

Hossein Borghaei, DO, chief of the Division of Thoracic Medical Oncology at Fox Chase Cancer Center, Philadelphia, was also unequivocal when asked if dual checkpoint blockade with chemotherapy should be considered the preferred first-line treatment option in patients with STK11 and/or KEAP1 mutations.

“No,” he said in a written comment. “The data and the hypothesis are very strong, but it is all based on retrospective clinical data, cell line data, and mouse models. We need a randomized study to test the hypothesis.”

Incidentally, Borghaei is on the steering committee for the TRITON trial. He shared this potential conflict of interest before praising Skoulidis and colleagues for their efforts, noting that the present findings underscore the broader importance of widespread tumor profiling and access to resultant data.

“This is a beautiful story that has developed over the last few years based on the research by the group from MD Anderson who has reported the current Nature article,” he said. “This highlights the possible utility of collecting sequencing data on [all] patients’ tumors. These sorts of understandings and new ideas could arise only if there is access to this information.”

The study was supported by AstraZeneca, the National Cancer Institute, the Gunnigar Fund, and others. The investigators disclosed additional relationships with Novartis, Merck, Amgen, and others. Deng disclosed relationships with Merck, BridgeBio, MJH Life Sciences, and others. Dy disclosed relationships with Eli Lilly and Company, Janssen Pharmaceuticals, Meru, and others. Malhotra has previously served as a consultant for AstraZeneca. Borghaei has served as a consultant for AstraZeneca and is on the steering committee for the TRITON trial.
 

A version of this article appeared on Medscape.com.

Many patients use cannabis to manage their cancer-related symptoms. However, research indicates that patients often do so without speaking to their oncologists first, and oncologists may be hesitant to broach the topic with their patients.

Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.

According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.

Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.

“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”

But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.

So, “let yourself off the hook,” Worster urged.

Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.

Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
 

Evidence on Cannabis During Cancer Care

A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.

In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.

Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.

The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.

The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.

The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.

Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.

There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.

The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
 

Talking to Patients About Cannabis

Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.

To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.

One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.

The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.

But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”

Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.

Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.

It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.

CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.

Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.

The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”

Worster disclosed that she is a medical consultant for EO Care.
 

A version of this article appeared on Medscape.com.

Many patients use cannabis to manage their cancer-related symptoms. However, research indicates that patients often do so without speaking to their oncologists first, and oncologists may be hesitant to broach the topic with their patients.

Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.

According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.

Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.

“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”

But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.

So, “let yourself off the hook,” Worster urged.

Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.

Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
 

Evidence on Cannabis During Cancer Care

A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.

In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.

Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.

The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.

The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.

The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.

Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.

There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.

The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
 

Talking to Patients About Cannabis

Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.

To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.

One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.

The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.

But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”

Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.

Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.

It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.

CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.

Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.

The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”

Worster disclosed that she is a medical consultant for EO Care.
 

A version of this article appeared on Medscape.com.

Many patients use cannabis to manage their cancer-related symptoms. However, research indicates that patients often do so without speaking to their oncologists first, and oncologists may be hesitant to broach the topic with their patients.

Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.

According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.

Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.

“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”

But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.

So, “let yourself off the hook,” Worster urged.

Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.

Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
 

Evidence on Cannabis During Cancer Care

A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.

In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.

Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.

The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.

The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.

The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.

Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.

There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.

The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
 

Talking to Patients About Cannabis

Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.

To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.

One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.

The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.

But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”

Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.

Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.

It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.

CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.

Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.

The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”

Worster disclosed that she is a medical consultant for EO Care.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has placed a partial clinical hold on the phase 3 PRESERVE-003 trial of BNT316/ONC-392 (gotistobart, BioNTech and OncoC4) for non–small cell lung cancer (NSCLC) due to varying results in patients with squamous and non-squamous NSCLC.

Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.

“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”

Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has placed a partial clinical hold on the phase 3 PRESERVE-003 trial of BNT316/ONC-392 (gotistobart, BioNTech and OncoC4) for non–small cell lung cancer (NSCLC) due to varying results in patients with squamous and non-squamous NSCLC.

Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.

“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”

Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has placed a partial clinical hold on the phase 3 PRESERVE-003 trial of BNT316/ONC-392 (gotistobart, BioNTech and OncoC4) for non–small cell lung cancer (NSCLC) due to varying results in patients with squamous and non-squamous NSCLC.

Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.

“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”

Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with early-stage triple-negative breast cancer (TNBC) and high immune infiltration showed improved disease-free survival (DFS) with adjuvant capecitabine. These “immune-hot” patients had a 5-year DFS rate of 96.9% compared with 79.4% in the control group.

METHODOLOGY:

• In some studies, adding extended capecitabine to standard adjuvant chemotherapy has been shown to improve DFS in patients with early-stage TNBC, and one subset analysis suggested improved outcomes were most strongly associated with high immune infiltration.
• Researchers conducted a retrospective analysis of CBCSG010, a randomized phase 3 clinical trial, to identify the specific population that benefited from adjuvant capecitabine by analyzing the immune infiltration status of the tumors.
• The CBCSGO10 study of 585 patients originally found adjuvant capecitabine improved 5-year survival in patients with TNBC by 5.9%.
• This analysis included 207 patients (capecitabine arm, n = 104; control arm, n = 103) with serial formalin-fixed, paraffin-embedded tumor specimens, of which RNA sequencing data were available from 36 patients (capecitabine, n = 24; control, n = 12).
• Transcriptome data on the tumor microenvironment were validated with immunohistochemical staining of two markers, programmed death-ligand 1 (PD-L1) and CD8, as well as stromal tumor-infiltrating lymphocytes (sTILs); patients with high PD-L1, CD8, and sTIL expression levels were defined as “immune hot.”

TAKEAWAY:

• Patients with TNBC and high immune infiltration treated with capecitabine had a 5-year DFS rate of 96.9% compared with 79.4% in the control group (hazard ratio [HR], 0.13; 95% CI, 0.03-0.52; P = .049).
• In the capecitabine group, the immune-hot patients had a higher 5-year DFS rate (96.9%) compared with immune-cold patients (76.4%; HR, 0.11; 95% CI, 0.04-0.29; P = .028).
• Gene ontology analysis showed greater enrichment of immune-related pathways in patients without recurrence in the capecitabine group, as well as higher expression of TYMP, a key liver enzyme in the metabolism of capecitabine.
• High expression levels of immune biomarkers PD-L1, CD8, and sTILs were associated with significantly improved DFS in the capecitabine group.

IN PRACTICE:

“Our study suggested that immune-hot patients with TNBC are more likely to benefit from adjuvant capecitabine and that combining immunotherapy with chemotherapy may be expected to be more effective in immune-hot patients,” wrote the study authors.

SOURCE:

The study was led by Wenya Wu, MMed, and Yunsong Yang, MD, at the Department of Breast Surgery, Fudan University Shanghai Cancer Center in Shanghai, People’s Republic of China. It was published online October 2024 in JNCCN — Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective nature of the sample collection limited the availability of RNA sequencing data. External verification was challenging due to limited accessibility of transcriptome data from patients treated with additional adjuvant capecitabine or standard chemotherapy alone. The criteria for identifying immune-hot tumors require further exploration and determination.

DISCLOSURES:

This study was funded by the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Shanghai Science and Technology Development Foundation. The authors disclosed no relevant conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Patients with early-stage triple-negative breast cancer (TNBC) and high immune infiltration showed improved disease-free survival (DFS) with adjuvant capecitabine. These “immune-hot” patients had a 5-year DFS rate of 96.9% compared with 79.4% in the control group.

METHODOLOGY:

• In some studies, adding extended capecitabine to standard adjuvant chemotherapy has been shown to improve DFS in patients with early-stage TNBC, and one subset analysis suggested improved outcomes were most strongly associated with high immune infiltration.
• Researchers conducted a retrospective analysis of CBCSG010, a randomized phase 3 clinical trial, to identify the specific population that benefited from adjuvant capecitabine by analyzing the immune infiltration status of the tumors.
• The CBCSGO10 study of 585 patients originally found adjuvant capecitabine improved 5-year survival in patients with TNBC by 5.9%.
• This analysis included 207 patients (capecitabine arm, n = 104; control arm, n = 103) with serial formalin-fixed, paraffin-embedded tumor specimens, of which RNA sequencing data were available from 36 patients (capecitabine, n = 24; control, n = 12).
• Transcriptome data on the tumor microenvironment were validated with immunohistochemical staining of two markers, programmed death-ligand 1 (PD-L1) and CD8, as well as stromal tumor-infiltrating lymphocytes (sTILs); patients with high PD-L1, CD8, and sTIL expression levels were defined as “immune hot.”

TAKEAWAY:

• Patients with TNBC and high immune infiltration treated with capecitabine had a 5-year DFS rate of 96.9% compared with 79.4% in the control group (hazard ratio [HR], 0.13; 95% CI, 0.03-0.52; P = .049).
• In the capecitabine group, the immune-hot patients had a higher 5-year DFS rate (96.9%) compared with immune-cold patients (76.4%; HR, 0.11; 95% CI, 0.04-0.29; P = .028).
• Gene ontology analysis showed greater enrichment of immune-related pathways in patients without recurrence in the capecitabine group, as well as higher expression of TYMP, a key liver enzyme in the metabolism of capecitabine.
• High expression levels of immune biomarkers PD-L1, CD8, and sTILs were associated with significantly improved DFS in the capecitabine group.

IN PRACTICE:

“Our study suggested that immune-hot patients with TNBC are more likely to benefit from adjuvant capecitabine and that combining immunotherapy with chemotherapy may be expected to be more effective in immune-hot patients,” wrote the study authors.

SOURCE:

The study was led by Wenya Wu, MMed, and Yunsong Yang, MD, at the Department of Breast Surgery, Fudan University Shanghai Cancer Center in Shanghai, People’s Republic of China. It was published online October 2024 in JNCCN — Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective nature of the sample collection limited the availability of RNA sequencing data. External verification was challenging due to limited accessibility of transcriptome data from patients treated with additional adjuvant capecitabine or standard chemotherapy alone. The criteria for identifying immune-hot tumors require further exploration and determination.

DISCLOSURES:

This study was funded by the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Shanghai Science and Technology Development Foundation. The authors disclosed no relevant conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Patients with early-stage triple-negative breast cancer (TNBC) and high immune infiltration showed improved disease-free survival (DFS) with adjuvant capecitabine. These “immune-hot” patients had a 5-year DFS rate of 96.9% compared with 79.4% in the control group.

METHODOLOGY:

• In some studies, adding extended capecitabine to standard adjuvant chemotherapy has been shown to improve DFS in patients with early-stage TNBC, and one subset analysis suggested improved outcomes were most strongly associated with high immune infiltration.
• Researchers conducted a retrospective analysis of CBCSG010, a randomized phase 3 clinical trial, to identify the specific population that benefited from adjuvant capecitabine by analyzing the immune infiltration status of the tumors.
• The CBCSGO10 study of 585 patients originally found adjuvant capecitabine improved 5-year survival in patients with TNBC by 5.9%.
• This analysis included 207 patients (capecitabine arm, n = 104; control arm, n = 103) with serial formalin-fixed, paraffin-embedded tumor specimens, of which RNA sequencing data were available from 36 patients (capecitabine, n = 24; control, n = 12).
• Transcriptome data on the tumor microenvironment were validated with immunohistochemical staining of two markers, programmed death-ligand 1 (PD-L1) and CD8, as well as stromal tumor-infiltrating lymphocytes (sTILs); patients with high PD-L1, CD8, and sTIL expression levels were defined as “immune hot.”

TAKEAWAY:

• Patients with TNBC and high immune infiltration treated with capecitabine had a 5-year DFS rate of 96.9% compared with 79.4% in the control group (hazard ratio [HR], 0.13; 95% CI, 0.03-0.52; P = .049).
• In the capecitabine group, the immune-hot patients had a higher 5-year DFS rate (96.9%) compared with immune-cold patients (76.4%; HR, 0.11; 95% CI, 0.04-0.29; P = .028).
• Gene ontology analysis showed greater enrichment of immune-related pathways in patients without recurrence in the capecitabine group, as well as higher expression of TYMP, a key liver enzyme in the metabolism of capecitabine.
• High expression levels of immune biomarkers PD-L1, CD8, and sTILs were associated with significantly improved DFS in the capecitabine group.

IN PRACTICE:

“Our study suggested that immune-hot patients with TNBC are more likely to benefit from adjuvant capecitabine and that combining immunotherapy with chemotherapy may be expected to be more effective in immune-hot patients,” wrote the study authors.

SOURCE:

The study was led by Wenya Wu, MMed, and Yunsong Yang, MD, at the Department of Breast Surgery, Fudan University Shanghai Cancer Center in Shanghai, People’s Republic of China. It was published online October 2024 in JNCCN — Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective nature of the sample collection limited the availability of RNA sequencing data. External verification was challenging due to limited accessibility of transcriptome data from patients treated with additional adjuvant capecitabine or standard chemotherapy alone. The criteria for identifying immune-hot tumors require further exploration and determination.

DISCLOSURES:

This study was funded by the National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Shanghai Science and Technology Development Foundation. The authors disclosed no relevant conflicts of interest.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

What do we do if we don’t like patients? We take the Hippocratic Oath as young students in Glasgow. We do that just before our graduation ceremony; we hold our hands up and repeat the Hippocratic Oath: “First, do no harm,” and so on.

What happens if we intensely dislike a patient? Is it possible to offer them the very best care? I was thinking back over a long career. I’ve been a cancer doctor for 40 years and I quite like saying that.

I can only think genuinely over a couple of times in which I’ve acted reflexively when a patient has done something awful. The couple of times it happened, it was just terrible racist comments to junior doctors who were with me. Extraordinarily dreadful things such as, “I don’t want to be touched by ...” or something of that sort.

Without really thinking about it, you react as a normal citizen and say, “That’s absolutely awful. Apologize immediately or leave the consultation room, and never ever come back again.” 

I remember that it happened once in Glasgow and once when I was a young professor in Birmingham, and it’s just an automatic gut reaction. The patient got a fright, and I immediately apologized and groveled around. In that relationship, we hold all the power, don’t we? Rather than being gentle about it, I was genuinely angry because of these ridiculous comments. 

Otherwise, I think most of the doctor-patient relationships are predicated on nonromantic love. I think patients want us to love them as one would a son, mother, father, or daughter, because if we do, then we will do better for them and we’ll pull out all the stops. “Placebo” means “I will please.” I think in the vast majority of cases, at least in our National Health Service (NHS), patients come with trust and a sense of wanting to build that relationship. That may be changing, but not for me. 

What about putting the boot on the other foot? What if the patients don’t like us rather than vice versa? As part of our accreditation appraisal process, from time to time we have to take patient surveys as to whether the patients felt that, after they had been seen in a consultation, they were treated with dignity, the quality of information given was appropriate, and they were treated with kindness. 

It’s an excellent exercise. Without bragging about it, patients objectively, according to these measures, appreciate the service that I give. It’s like getting five-star reviews on Trustpilot, or whatever these things are, that allow you to review car salesmen and so on. I have always had five-star reviews across the board. 

That, again, I thought was just a feature of that relationship, of patients wanting to please. These are patients who had been treated, who were in the outpatient department, who were in the midst of battle. Still, the scores are very high. I speak to my colleagues and that’s not uniformly the case. Patients actually do use these feedback forms, I think in a positive rather than negative way, reflecting back on the way that they were treated.

It has caused some of my colleagues to think quite hard about their personal style and approach to patients. That sense of feedback is important. 

What about losing trust? If that’s at the heart of everything that we do, then what would be an objective measure of losing trust? Again, in our healthcare system, it has been exceedingly unusual for a patient to request a second opinion. Now, that’s changing. The government is trying to change it. Leaders of the NHS are trying to change it so that patients feel assured that they can seek second opinions.

Again, in all the years I’ve been a cancer doctor, it has been incredibly infrequent that somebody has sought a second opinion after I’ve said something. That may be a measure of trust. Again, I’ve lived through an NHS in which seeking second opinions was something of a rarity. 

I’d be really interested to see what you think. In your own sphere of healthcare practice, is it possible for us to look after patients that we don’t like, or should we be honest and say, “I don’t like you. Our relationship has broken down. I want you to be seen by a colleague,” or “I want you to be nursed by somebody else”?

Has that happened? Is that something that you think is common or may become more common? What about when trust breaks down the other way? Can you think of instances in which the relationship, for whatever reason, just didn’t work and the patient had to move on because of that loss of trust and what underpinned it? I’d be really interested to know. 

I seek to be informed rather than the other way around. Can we truly look after patients that we don’t like or can we rise above it as Hippocrates might have done? 

Thanks for listening, as always. For the time being, over and out.

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, and Roche.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

What do we do if we don’t like patients? We take the Hippocratic Oath as young students in Glasgow. We do that just before our graduation ceremony; we hold our hands up and repeat the Hippocratic Oath: “First, do no harm,” and so on.

What happens if we intensely dislike a patient? Is it possible to offer them the very best care? I was thinking back over a long career. I’ve been a cancer doctor for 40 years and I quite like saying that.

I can only think genuinely over a couple of times in which I’ve acted reflexively when a patient has done something awful. The couple of times it happened, it was just terrible racist comments to junior doctors who were with me. Extraordinarily dreadful things such as, “I don’t want to be touched by ...” or something of that sort.

Without really thinking about it, you react as a normal citizen and say, “That’s absolutely awful. Apologize immediately or leave the consultation room, and never ever come back again.” 

I remember that it happened once in Glasgow and once when I was a young professor in Birmingham, and it’s just an automatic gut reaction. The patient got a fright, and I immediately apologized and groveled around. In that relationship, we hold all the power, don’t we? Rather than being gentle about it, I was genuinely angry because of these ridiculous comments. 

Otherwise, I think most of the doctor-patient relationships are predicated on nonromantic love. I think patients want us to love them as one would a son, mother, father, or daughter, because if we do, then we will do better for them and we’ll pull out all the stops. “Placebo” means “I will please.” I think in the vast majority of cases, at least in our National Health Service (NHS), patients come with trust and a sense of wanting to build that relationship. That may be changing, but not for me. 

What about putting the boot on the other foot? What if the patients don’t like us rather than vice versa? As part of our accreditation appraisal process, from time to time we have to take patient surveys as to whether the patients felt that, after they had been seen in a consultation, they were treated with dignity, the quality of information given was appropriate, and they were treated with kindness. 

It’s an excellent exercise. Without bragging about it, patients objectively, according to these measures, appreciate the service that I give. It’s like getting five-star reviews on Trustpilot, or whatever these things are, that allow you to review car salesmen and so on. I have always had five-star reviews across the board. 

That, again, I thought was just a feature of that relationship, of patients wanting to please. These are patients who had been treated, who were in the outpatient department, who were in the midst of battle. Still, the scores are very high. I speak to my colleagues and that’s not uniformly the case. Patients actually do use these feedback forms, I think in a positive rather than negative way, reflecting back on the way that they were treated.

It has caused some of my colleagues to think quite hard about their personal style and approach to patients. That sense of feedback is important. 

What about losing trust? If that’s at the heart of everything that we do, then what would be an objective measure of losing trust? Again, in our healthcare system, it has been exceedingly unusual for a patient to request a second opinion. Now, that’s changing. The government is trying to change it. Leaders of the NHS are trying to change it so that patients feel assured that they can seek second opinions.

Again, in all the years I’ve been a cancer doctor, it has been incredibly infrequent that somebody has sought a second opinion after I’ve said something. That may be a measure of trust. Again, I’ve lived through an NHS in which seeking second opinions was something of a rarity. 

I’d be really interested to see what you think. In your own sphere of healthcare practice, is it possible for us to look after patients that we don’t like, or should we be honest and say, “I don’t like you. Our relationship has broken down. I want you to be seen by a colleague,” or “I want you to be nursed by somebody else”?

Has that happened? Is that something that you think is common or may become more common? What about when trust breaks down the other way? Can you think of instances in which the relationship, for whatever reason, just didn’t work and the patient had to move on because of that loss of trust and what underpinned it? I’d be really interested to know. 

I seek to be informed rather than the other way around. Can we truly look after patients that we don’t like or can we rise above it as Hippocrates might have done? 

Thanks for listening, as always. For the time being, over and out.

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, and Roche.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

What do we do if we don’t like patients? We take the Hippocratic Oath as young students in Glasgow. We do that just before our graduation ceremony; we hold our hands up and repeat the Hippocratic Oath: “First, do no harm,” and so on.

What happens if we intensely dislike a patient? Is it possible to offer them the very best care? I was thinking back over a long career. I’ve been a cancer doctor for 40 years and I quite like saying that.

I can only think genuinely over a couple of times in which I’ve acted reflexively when a patient has done something awful. The couple of times it happened, it was just terrible racist comments to junior doctors who were with me. Extraordinarily dreadful things such as, “I don’t want to be touched by ...” or something of that sort.

Without really thinking about it, you react as a normal citizen and say, “That’s absolutely awful. Apologize immediately or leave the consultation room, and never ever come back again.” 

I remember that it happened once in Glasgow and once when I was a young professor in Birmingham, and it’s just an automatic gut reaction. The patient got a fright, and I immediately apologized and groveled around. In that relationship, we hold all the power, don’t we? Rather than being gentle about it, I was genuinely angry because of these ridiculous comments. 

Otherwise, I think most of the doctor-patient relationships are predicated on nonromantic love. I think patients want us to love them as one would a son, mother, father, or daughter, because if we do, then we will do better for them and we’ll pull out all the stops. “Placebo” means “I will please.” I think in the vast majority of cases, at least in our National Health Service (NHS), patients come with trust and a sense of wanting to build that relationship. That may be changing, but not for me. 

What about putting the boot on the other foot? What if the patients don’t like us rather than vice versa? As part of our accreditation appraisal process, from time to time we have to take patient surveys as to whether the patients felt that, after they had been seen in a consultation, they were treated with dignity, the quality of information given was appropriate, and they were treated with kindness. 

It’s an excellent exercise. Without bragging about it, patients objectively, according to these measures, appreciate the service that I give. It’s like getting five-star reviews on Trustpilot, or whatever these things are, that allow you to review car salesmen and so on. I have always had five-star reviews across the board. 

That, again, I thought was just a feature of that relationship, of patients wanting to please. These are patients who had been treated, who were in the outpatient department, who were in the midst of battle. Still, the scores are very high. I speak to my colleagues and that’s not uniformly the case. Patients actually do use these feedback forms, I think in a positive rather than negative way, reflecting back on the way that they were treated.

It has caused some of my colleagues to think quite hard about their personal style and approach to patients. That sense of feedback is important. 

What about losing trust? If that’s at the heart of everything that we do, then what would be an objective measure of losing trust? Again, in our healthcare system, it has been exceedingly unusual for a patient to request a second opinion. Now, that’s changing. The government is trying to change it. Leaders of the NHS are trying to change it so that patients feel assured that they can seek second opinions.

Again, in all the years I’ve been a cancer doctor, it has been incredibly infrequent that somebody has sought a second opinion after I’ve said something. That may be a measure of trust. Again, I’ve lived through an NHS in which seeking second opinions was something of a rarity. 

I’d be really interested to see what you think. In your own sphere of healthcare practice, is it possible for us to look after patients that we don’t like, or should we be honest and say, “I don’t like you. Our relationship has broken down. I want you to be seen by a colleague,” or “I want you to be nursed by somebody else”?

Has that happened? Is that something that you think is common or may become more common? What about when trust breaks down the other way? Can you think of instances in which the relationship, for whatever reason, just didn’t work and the patient had to move on because of that loss of trust and what underpinned it? I’d be really interested to know. 

I seek to be informed rather than the other way around. Can we truly look after patients that we don’t like or can we rise above it as Hippocrates might have done? 

Thanks for listening, as always. For the time being, over and out.

Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, and Roche.

A version of this article appeared on Medscape.com.

TOPLINE:

The Fracture Risk Assessment Tool (FRAX), with bone mineral density, predicts the risk for major osteoporotic fractures and hip fractures in patients with cancer, but FRAX without bone mineral density slightly overestimates these risks, a new analysis found.

METHODOLOGY:

• Cancer-specific guidelines recommend using FRAX to assess fracture risk, but its applicability in patients with cancer remains unclear.
• This retrospective cohort study included 9877 patients with cancer (mean age, 67.1 years) and 45,875 matched control individuals without cancer (mean age, 66.2 years). All participants had dual-energy x-ray absorptiometry (DXA) scans.
• Researchers collected data on bone mineral density and fractures. The 10-year probabilities of major osteoporotic fractures and hip fractures were calculated using FRAX, and the observed 10-year probabilities of these fractures were compared with FRAX-derived probabilities.
• Compared with individuals without cancer, patients with cancer had a shorter mean follow-up duration (8.5 vs 7.6 years), a slightly higher mean body mass index, and a higher percentage of parental hip fractures (7.0% vs 8.2%); additionally, patients with cancer were more likely to have secondary causes of osteoporosis (10% vs 38.4%) and less likely to receive osteoporosis medication (9.9% vs 4.2%).

TAKEAWAY:

• Compared with individuals without cancer, patients with cancer had a significantly higher incidence rate of major fractures (12.9 vs 14.5 per 1000 person-years) and hip fractures (3.5 vs 4.2 per 1000 person-years).
• FRAX with bone mineral density exhibited excellent calibration for predicting major osteoporotic fractures (slope, 1.03) and hip fractures (0.97) in patients with cancer, regardless of the site of cancer diagnosis. FRAX without bone mineral density, however, underestimated the risk for both major (0.87) and hip fractures (0.72).
• In patients with cancer, FRAX with bone mineral density findings were associated with incident major osteoporotic fractures (hazard ratio [HR] per SD, 1.84) and hip fractures (HR per SD, 3.61).
• When models were adjusted for FRAX with bone mineral density, patients with cancer had an increased risk for both major osteoporotic fractures (HR, 1.17) and hip fractures (HR, 1.30). No difference was found in the risk for fracture between patients with and individuals without cancer when the models were adjusted for FRAX without bone mineral density, even when considering osteoporosis medication use.

IN PRACTICE:

“This retrospective cohort study demonstrates that individuals with cancer are at higher risk of fracture than individuals without cancer and that FRAX, particularly with BMD [bone mineral density], may accurately predict fracture risk in this population. These results, along with the known mortality risk of osteoporotic fractures among cancer survivors, further emphasize the clinical importance of closing the current osteoporosis care gap among cancer survivors,” the authors wrote.

SOURCE:

This study, led by Carrie Ye, MD, MPH, University of Alberta, Edmonton, Alberta, Canada, was published online in JAMA Oncology.

LIMITATIONS:

This study cohort included a selected group of cancer survivors who were referred for DXA scans and may not represent the general cancer population. The cohort consisted predominantly of women, limiting the generalizability to men with cancer. Given the heterogeneity of the population, the findings may not be applicable to all cancer subgroups. Information on cancer stage or the presence of bone metastases at the time of fracture risk assessment was lacking, which could have affected the findings.

DISCLOSURES:

This study was funded by the CancerCare Manitoba Foundation. Three authors reported having ties with various sources, including two who received grants from various organizations.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The Fracture Risk Assessment Tool (FRAX), with bone mineral density, predicts the risk for major osteoporotic fractures and hip fractures in patients with cancer, but FRAX without bone mineral density slightly overestimates these risks, a new analysis found.

METHODOLOGY:

• Cancer-specific guidelines recommend using FRAX to assess fracture risk, but its applicability in patients with cancer remains unclear.
• This retrospective cohort study included 9877 patients with cancer (mean age, 67.1 years) and 45,875 matched control individuals without cancer (mean age, 66.2 years). All participants had dual-energy x-ray absorptiometry (DXA) scans.
• Researchers collected data on bone mineral density and fractures. The 10-year probabilities of major osteoporotic fractures and hip fractures were calculated using FRAX, and the observed 10-year probabilities of these fractures were compared with FRAX-derived probabilities.
• Compared with individuals without cancer, patients with cancer had a shorter mean follow-up duration (8.5 vs 7.6 years), a slightly higher mean body mass index, and a higher percentage of parental hip fractures (7.0% vs 8.2%); additionally, patients with cancer were more likely to have secondary causes of osteoporosis (10% vs 38.4%) and less likely to receive osteoporosis medication (9.9% vs 4.2%).

TAKEAWAY:

• Compared with individuals without cancer, patients with cancer had a significantly higher incidence rate of major fractures (12.9 vs 14.5 per 1000 person-years) and hip fractures (3.5 vs 4.2 per 1000 person-years).
• FRAX with bone mineral density exhibited excellent calibration for predicting major osteoporotic fractures (slope, 1.03) and hip fractures (0.97) in patients with cancer, regardless of the site of cancer diagnosis. FRAX without bone mineral density, however, underestimated the risk for both major (0.87) and hip fractures (0.72).
• In patients with cancer, FRAX with bone mineral density findings were associated with incident major osteoporotic fractures (hazard ratio [HR] per SD, 1.84) and hip fractures (HR per SD, 3.61).
• When models were adjusted for FRAX with bone mineral density, patients with cancer had an increased risk for both major osteoporotic fractures (HR, 1.17) and hip fractures (HR, 1.30). No difference was found in the risk for fracture between patients with and individuals without cancer when the models were adjusted for FRAX without bone mineral density, even when considering osteoporosis medication use.

IN PRACTICE:

“This retrospective cohort study demonstrates that individuals with cancer are at higher risk of fracture than individuals without cancer and that FRAX, particularly with BMD [bone mineral density], may accurately predict fracture risk in this population. These results, along with the known mortality risk of osteoporotic fractures among cancer survivors, further emphasize the clinical importance of closing the current osteoporosis care gap among cancer survivors,” the authors wrote.

SOURCE:

This study, led by Carrie Ye, MD, MPH, University of Alberta, Edmonton, Alberta, Canada, was published online in JAMA Oncology.

LIMITATIONS:

This study cohort included a selected group of cancer survivors who were referred for DXA scans and may not represent the general cancer population. The cohort consisted predominantly of women, limiting the generalizability to men with cancer. Given the heterogeneity of the population, the findings may not be applicable to all cancer subgroups. Information on cancer stage or the presence of bone metastases at the time of fracture risk assessment was lacking, which could have affected the findings.

DISCLOSURES:

This study was funded by the CancerCare Manitoba Foundation. Three authors reported having ties with various sources, including two who received grants from various organizations.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

The Fracture Risk Assessment Tool (FRAX), with bone mineral density, predicts the risk for major osteoporotic fractures and hip fractures in patients with cancer, but FRAX without bone mineral density slightly overestimates these risks, a new analysis found.

METHODOLOGY:

• Cancer-specific guidelines recommend using FRAX to assess fracture risk, but its applicability in patients with cancer remains unclear.
• This retrospective cohort study included 9877 patients with cancer (mean age, 67.1 years) and 45,875 matched control individuals without cancer (mean age, 66.2 years). All participants had dual-energy x-ray absorptiometry (DXA) scans.
• Researchers collected data on bone mineral density and fractures. The 10-year probabilities of major osteoporotic fractures and hip fractures were calculated using FRAX, and the observed 10-year probabilities of these fractures were compared with FRAX-derived probabilities.
• Compared with individuals without cancer, patients with cancer had a shorter mean follow-up duration (8.5 vs 7.6 years), a slightly higher mean body mass index, and a higher percentage of parental hip fractures (7.0% vs 8.2%); additionally, patients with cancer were more likely to have secondary causes of osteoporosis (10% vs 38.4%) and less likely to receive osteoporosis medication (9.9% vs 4.2%).

TAKEAWAY:

• Compared with individuals without cancer, patients with cancer had a significantly higher incidence rate of major fractures (12.9 vs 14.5 per 1000 person-years) and hip fractures (3.5 vs 4.2 per 1000 person-years).
• FRAX with bone mineral density exhibited excellent calibration for predicting major osteoporotic fractures (slope, 1.03) and hip fractures (0.97) in patients with cancer, regardless of the site of cancer diagnosis. FRAX without bone mineral density, however, underestimated the risk for both major (0.87) and hip fractures (0.72).
• In patients with cancer, FRAX with bone mineral density findings were associated with incident major osteoporotic fractures (hazard ratio [HR] per SD, 1.84) and hip fractures (HR per SD, 3.61).
• When models were adjusted for FRAX with bone mineral density, patients with cancer had an increased risk for both major osteoporotic fractures (HR, 1.17) and hip fractures (HR, 1.30). No difference was found in the risk for fracture between patients with and individuals without cancer when the models were adjusted for FRAX without bone mineral density, even when considering osteoporosis medication use.

IN PRACTICE:

“This retrospective cohort study demonstrates that individuals with cancer are at higher risk of fracture than individuals without cancer and that FRAX, particularly with BMD [bone mineral density], may accurately predict fracture risk in this population. These results, along with the known mortality risk of osteoporotic fractures among cancer survivors, further emphasize the clinical importance of closing the current osteoporosis care gap among cancer survivors,” the authors wrote.

SOURCE:

This study, led by Carrie Ye, MD, MPH, University of Alberta, Edmonton, Alberta, Canada, was published online in JAMA Oncology.

LIMITATIONS:

This study cohort included a selected group of cancer survivors who were referred for DXA scans and may not represent the general cancer population. The cohort consisted predominantly of women, limiting the generalizability to men with cancer. Given the heterogeneity of the population, the findings may not be applicable to all cancer subgroups. Information on cancer stage or the presence of bone metastases at the time of fracture risk assessment was lacking, which could have affected the findings.

DISCLOSURES:

This study was funded by the CancerCare Manitoba Foundation. Three authors reported having ties with various sources, including two who received grants from various organizations.
 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

In patients with localized prostate cancer, stereotactic body radiotherapy (SBRT) was associated with better urinary continence and sexual function, but slightly worse bowel function, compared with radical prostatectomy, according to a phase 3, open-label, randomized trial evaluating quality-of-life outcomes.

METHODOLOGY:

• Compared with prostatectomy, radiotherapy may offer better urinary and sexual outcomes but a higher risk for bowel toxicity in patients with localized prostate cancer. However, a comparison has not been performed in a randomized trial using more modern treatment options, such as SBRT.
• Researchers conducted the multicenter PACE-A trial to compare and evaluate quality-of-life outcomes among 123 patients (median age, 65.5 years) with low- to intermediate-risk localized prostate cancer who were randomly assigned to undergo either SBRT (n = 63) or radical prostatectomy (n = 60).
• Of the 123 patients, 97 (79%) had a Gleason score of 3+4 and 116 (94%) had National Comprehensive Cancer Network intermediate risk. The median follow-up was 60.7 months.
• The co–primary endpoints were urinary continence, measured by the number of absorbent urinary pads required per day, and bowel function, assessed using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26).
• Secondary endpoints included erectile function (measured using the International Index of Erectile Function 5 questionnaire) , clinician-reported genitourinary and gastrointestinal toxicity, and International Prostate Symptom Score. Other patient-reported outcomes included EPIC-26 domain scores for urinary irritative/obstructive symptoms, and overall urinary, bowel, and sexual issues.

TAKEAWAY:

• At 2 years, only 6.5% (three of 46) of patients who ultimately received SBRT used one or more urinary pads daily compared with 50% (16 of 32) of patients who underwent prostatectomy (P < .001). Patients in the prostatectomy group reported worse EPIC-26 urinary incontinence domain scores (median, 77.3 vs 100; P = .003).
• Patients who underwent prostatectomy also had significantly worse sexual function scores (median, 18 vs 62.5 with SBRT; P < .001). Erectile dysfunction events of grade 2 or higher were significantly more common in patients who underwent prostatectomy (63% vs 18%).
• However, at 2 years, the bowel domain scores in the prostatectomy group were significantly higher than in the SBRT group (median, 100 vs 87.5), with a mean difference of 8.9.
• Overall, clinician-reported genitourinary and gastrointestinal toxicities were low in both treatment groups.

IN PRACTICE:

“PACE-A provides level 1 evidence of better outcomes of urinary continence and sexual function with worse bowel bother for SBRT, compared with prostatectomy,” the authors wrote, adding that the trial “provides contemporary toxicity estimates to optimize treatment decisions and maximize individual quality of life.”

SOURCE:

The study, led by Nicholas van As, of The Royal Marsden Hospital and The Institute of Cancer Research in London, was published online in European Urology.

LIMITATIONS:

The small sample size and differential dropout from allocated treatment could have introduced bias. Data completeness was another limitation.

DISCLOSURES:

The study was supported by grants from the Royal Marsden NHS Foundation Trust. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

In patients with localized prostate cancer, stereotactic body radiotherapy (SBRT) was associated with better urinary continence and sexual function, but slightly worse bowel function, compared with radical prostatectomy, according to a phase 3, open-label, randomized trial evaluating quality-of-life outcomes.

METHODOLOGY:

• Compared with prostatectomy, radiotherapy may offer better urinary and sexual outcomes but a higher risk for bowel toxicity in patients with localized prostate cancer. However, a comparison has not been performed in a randomized trial using more modern treatment options, such as SBRT.
• Researchers conducted the multicenter PACE-A trial to compare and evaluate quality-of-life outcomes among 123 patients (median age, 65.5 years) with low- to intermediate-risk localized prostate cancer who were randomly assigned to undergo either SBRT (n = 63) or radical prostatectomy (n = 60).
• Of the 123 patients, 97 (79%) had a Gleason score of 3+4 and 116 (94%) had National Comprehensive Cancer Network intermediate risk. The median follow-up was 60.7 months.
• The co–primary endpoints were urinary continence, measured by the number of absorbent urinary pads required per day, and bowel function, assessed using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26).
• Secondary endpoints included erectile function (measured using the International Index of Erectile Function 5 questionnaire) , clinician-reported genitourinary and gastrointestinal toxicity, and International Prostate Symptom Score. Other patient-reported outcomes included EPIC-26 domain scores for urinary irritative/obstructive symptoms, and overall urinary, bowel, and sexual issues.

TAKEAWAY:

• At 2 years, only 6.5% (three of 46) of patients who ultimately received SBRT used one or more urinary pads daily compared with 50% (16 of 32) of patients who underwent prostatectomy (P < .001). Patients in the prostatectomy group reported worse EPIC-26 urinary incontinence domain scores (median, 77.3 vs 100; P = .003).
• Patients who underwent prostatectomy also had significantly worse sexual function scores (median, 18 vs 62.5 with SBRT; P < .001). Erectile dysfunction events of grade 2 or higher were significantly more common in patients who underwent prostatectomy (63% vs 18%).
• However, at 2 years, the bowel domain scores in the prostatectomy group were significantly higher than in the SBRT group (median, 100 vs 87.5), with a mean difference of 8.9.
• Overall, clinician-reported genitourinary and gastrointestinal toxicities were low in both treatment groups.

IN PRACTICE:

“PACE-A provides level 1 evidence of better outcomes of urinary continence and sexual function with worse bowel bother for SBRT, compared with prostatectomy,” the authors wrote, adding that the trial “provides contemporary toxicity estimates to optimize treatment decisions and maximize individual quality of life.”

SOURCE:

The study, led by Nicholas van As, of The Royal Marsden Hospital and The Institute of Cancer Research in London, was published online in European Urology.

LIMITATIONS:

The small sample size and differential dropout from allocated treatment could have introduced bias. Data completeness was another limitation.

DISCLOSURES:

The study was supported by grants from the Royal Marsden NHS Foundation Trust. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

In patients with localized prostate cancer, stereotactic body radiotherapy (SBRT) was associated with better urinary continence and sexual function, but slightly worse bowel function, compared with radical prostatectomy, according to a phase 3, open-label, randomized trial evaluating quality-of-life outcomes.

METHODOLOGY:

• Compared with prostatectomy, radiotherapy may offer better urinary and sexual outcomes but a higher risk for bowel toxicity in patients with localized prostate cancer. However, a comparison has not been performed in a randomized trial using more modern treatment options, such as SBRT.
• Researchers conducted the multicenter PACE-A trial to compare and evaluate quality-of-life outcomes among 123 patients (median age, 65.5 years) with low- to intermediate-risk localized prostate cancer who were randomly assigned to undergo either SBRT (n = 63) or radical prostatectomy (n = 60).
• Of the 123 patients, 97 (79%) had a Gleason score of 3+4 and 116 (94%) had National Comprehensive Cancer Network intermediate risk. The median follow-up was 60.7 months.
• The co–primary endpoints were urinary continence, measured by the number of absorbent urinary pads required per day, and bowel function, assessed using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26).
• Secondary endpoints included erectile function (measured using the International Index of Erectile Function 5 questionnaire) , clinician-reported genitourinary and gastrointestinal toxicity, and International Prostate Symptom Score. Other patient-reported outcomes included EPIC-26 domain scores for urinary irritative/obstructive symptoms, and overall urinary, bowel, and sexual issues.

TAKEAWAY:

• At 2 years, only 6.5% (three of 46) of patients who ultimately received SBRT used one or more urinary pads daily compared with 50% (16 of 32) of patients who underwent prostatectomy (P < .001). Patients in the prostatectomy group reported worse EPIC-26 urinary incontinence domain scores (median, 77.3 vs 100; P = .003).
• Patients who underwent prostatectomy also had significantly worse sexual function scores (median, 18 vs 62.5 with SBRT; P < .001). Erectile dysfunction events of grade 2 or higher were significantly more common in patients who underwent prostatectomy (63% vs 18%).
• However, at 2 years, the bowel domain scores in the prostatectomy group were significantly higher than in the SBRT group (median, 100 vs 87.5), with a mean difference of 8.9.
• Overall, clinician-reported genitourinary and gastrointestinal toxicities were low in both treatment groups.

IN PRACTICE:

“PACE-A provides level 1 evidence of better outcomes of urinary continence and sexual function with worse bowel bother for SBRT, compared with prostatectomy,” the authors wrote, adding that the trial “provides contemporary toxicity estimates to optimize treatment decisions and maximize individual quality of life.”

SOURCE:

The study, led by Nicholas van As, of The Royal Marsden Hospital and The Institute of Cancer Research in London, was published online in European Urology.

LIMITATIONS:

The small sample size and differential dropout from allocated treatment could have introduced bias. Data completeness was another limitation.

DISCLOSURES:

The study was supported by grants from the Royal Marsden NHS Foundation Trust. Several authors reported having various ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.