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Inside the Patient-Oncologist Bond: Why It’s Often So Strong
Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.
“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”
That was 21 years ago. Today, her current cancer status is “no evidence of disease.”
Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.
In that time,
“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.
Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.
The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.
Gerber isn’t alone in calling out the depth of the oncologist-patient bond.
Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.
“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.
Connecting Through Stress
Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.
Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.
The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.
“I consider my patient’s battles to be my battles,” Khan wrote.
The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.
According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.
The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.
With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”
What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.
“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.
In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.
“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”
A ‘Special Relationship’
Ralph V. Boccia, MD, is often asked what he does.
The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.
“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”
Boccia thinks about one long-term patient who captures this bond.
Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.
Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.
Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.
“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”
Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.
Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.
Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.
More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.
“He has kept me alive,” said Pinson.
The Dying Patient
Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.
After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.
Several months later, Vyas was called for an inpatient consult. It was the same woman.
Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.
The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.
“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”
From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.
For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.
“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.
Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.
Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.
“Doc, I don’t want to die and my kids find me dead. What can we do about it?”
Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.
When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”
But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”
Khan had no relevant disclosures. Boccia and Vyas had no disclosures.
A version of this article appeared on Medscape.com.
Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.
“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”
That was 21 years ago. Today, her current cancer status is “no evidence of disease.”
Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.
In that time,
“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.
Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.
The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.
Gerber isn’t alone in calling out the depth of the oncologist-patient bond.
Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.
“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.
Connecting Through Stress
Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.
Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.
The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.
“I consider my patient’s battles to be my battles,” Khan wrote.
The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.
According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.
The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.
With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”
What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.
“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.
In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.
“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”
A ‘Special Relationship’
Ralph V. Boccia, MD, is often asked what he does.
The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.
“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”
Boccia thinks about one long-term patient who captures this bond.
Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.
Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.
Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.
“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”
Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.
Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.
Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.
More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.
“He has kept me alive,” said Pinson.
The Dying Patient
Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.
After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.
Several months later, Vyas was called for an inpatient consult. It was the same woman.
Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.
The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.
“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”
From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.
For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.
“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.
Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.
Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.
“Doc, I don’t want to die and my kids find me dead. What can we do about it?”
Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.
When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”
But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”
Khan had no relevant disclosures. Boccia and Vyas had no disclosures.
A version of this article appeared on Medscape.com.
Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.
“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”
That was 21 years ago. Today, her current cancer status is “no evidence of disease.”
Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.
In that time,
“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.
Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.
The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.
Gerber isn’t alone in calling out the depth of the oncologist-patient bond.
Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.
“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.
Connecting Through Stress
Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.
Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.
The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.
“I consider my patient’s battles to be my battles,” Khan wrote.
The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.
According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.
The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.
With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”
What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.
“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.
In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.
“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”
A ‘Special Relationship’
Ralph V. Boccia, MD, is often asked what he does.
The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.
“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”
Boccia thinks about one long-term patient who captures this bond.
Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.
Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.
Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.
“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”
Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.
Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.
Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.
More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.
“He has kept me alive,” said Pinson.
The Dying Patient
Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.
After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.
Several months later, Vyas was called for an inpatient consult. It was the same woman.
Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.
The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.
“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”
From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.
For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.
“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.
Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.
Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.
“Doc, I don’t want to die and my kids find me dead. What can we do about it?”
Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.
When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”
But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”
Khan had no relevant disclosures. Boccia and Vyas had no disclosures.
A version of this article appeared on Medscape.com.
Michigan Oncologist Charged in Scheme to Illegally Sell Cancer Drugs
In late October, a federal grand jury charged a Detroit-area medical oncologist Naveed Aslam, MD, in an indictment for his part in a scheme to illegally sell cancer drugs.
According to the indictment, Aslam acquired and sold more than $17 million in cancer drugs and personally netted more than $2.5 million during the scheme.
The charges against Aslam, filed on October 23 in the US District Court for the Eastern District of Michigan, include 10 counts of illegally selling or trading prescription drugs and one count of conspiring to do so.
“Dr. Aslam’s alleged participation in this scheme not only allowed him to profit unlawfully from the sale of cancer drugs but it also posed a serious threat by potentially placing these medications into the wrong hands,” Cheyvoryea Gibson, special agent in charge of the FBI in Michigan, said in a press release announcing the indictment.
The investigation is being conducted jointly by the FBI, the US Food and Drug Administration (FDA), the US Department of Health and Human Services Office of Inspector General, and Homeland Security Investigations.
The indictment alleges that Aslam was recruited by an unnamed operator of a Michigan corporation that engaged in business as a retail pharmacy and in the wholesale distribution of expensive prescription drugs, largely oncology drugs.
According to the indictment, Aslam and the operator came to an agreement where Aslam would purchase these expensive drugs from an authorized distributor under the false pretense that he was going to prescribe them to patients.
Instead, Aslam allegedly “sold and transferred the prescription drugs” to or through the Michigan business, with involvement from the unnamed operator and a second unnamed individual.
The unnamed individuals “identified customers interested in buying prescription cancer drugs” and “communicated with Dr. Aslam about what cancer drugs were requested,” according to the press release. “Dr. Aslam used his access to certain cancer drugs through his medical practice, Somerset Hematology and Oncology, P.C., to order and purchase the cancer drugs from his supplier.”
The indictment lays out that Aslam allegedly profited from this scheme in several ways, which included charging the Michigan business more than he paid the distributor for the drugs, sharing the profits when the business resold the drugs at a markup, and receiving rebates and discounts from the distributor “based on the amount of qualifying drugs he purchased and resold.”
According to the indictment, the scheme ran from early 2019 to mid-2023 and included four antibody drug conjugates — trastuzumab deruxtecan (Enhertu), enfortumab vedotin (Padcev), tisotumab vedotin (Tivdak), and sacituzumab govitecan (Trodelvy) — and the monoclonal antibody mogamulizumab (Poteligeo) for cutaneous T-cell lymphoma.
By working with Aslam, the operatives “obtained prescription drugs from an authorized distributor that they would not otherwise have been permitted to purchase, and which they were able to sell at a profit,” according to the indictment.
Both the prosecuting assistant US attorney, Andrew Lievense, and Aslam’s defense lawyer, Daniel Dena, declined to comment for this news organization.
The prosecutor is seeking to recoup the more than $2.5 million Aslam allegedly pocketed, according to the indictment. The press release also noted that an “indictment is only a charge and is not evidence of guilt.”
A version of this article first appeared on Medscape.com.
In late October, a federal grand jury charged a Detroit-area medical oncologist Naveed Aslam, MD, in an indictment for his part in a scheme to illegally sell cancer drugs.
According to the indictment, Aslam acquired and sold more than $17 million in cancer drugs and personally netted more than $2.5 million during the scheme.
The charges against Aslam, filed on October 23 in the US District Court for the Eastern District of Michigan, include 10 counts of illegally selling or trading prescription drugs and one count of conspiring to do so.
“Dr. Aslam’s alleged participation in this scheme not only allowed him to profit unlawfully from the sale of cancer drugs but it also posed a serious threat by potentially placing these medications into the wrong hands,” Cheyvoryea Gibson, special agent in charge of the FBI in Michigan, said in a press release announcing the indictment.
The investigation is being conducted jointly by the FBI, the US Food and Drug Administration (FDA), the US Department of Health and Human Services Office of Inspector General, and Homeland Security Investigations.
The indictment alleges that Aslam was recruited by an unnamed operator of a Michigan corporation that engaged in business as a retail pharmacy and in the wholesale distribution of expensive prescription drugs, largely oncology drugs.
According to the indictment, Aslam and the operator came to an agreement where Aslam would purchase these expensive drugs from an authorized distributor under the false pretense that he was going to prescribe them to patients.
Instead, Aslam allegedly “sold and transferred the prescription drugs” to or through the Michigan business, with involvement from the unnamed operator and a second unnamed individual.
The unnamed individuals “identified customers interested in buying prescription cancer drugs” and “communicated with Dr. Aslam about what cancer drugs were requested,” according to the press release. “Dr. Aslam used his access to certain cancer drugs through his medical practice, Somerset Hematology and Oncology, P.C., to order and purchase the cancer drugs from his supplier.”
The indictment lays out that Aslam allegedly profited from this scheme in several ways, which included charging the Michigan business more than he paid the distributor for the drugs, sharing the profits when the business resold the drugs at a markup, and receiving rebates and discounts from the distributor “based on the amount of qualifying drugs he purchased and resold.”
According to the indictment, the scheme ran from early 2019 to mid-2023 and included four antibody drug conjugates — trastuzumab deruxtecan (Enhertu), enfortumab vedotin (Padcev), tisotumab vedotin (Tivdak), and sacituzumab govitecan (Trodelvy) — and the monoclonal antibody mogamulizumab (Poteligeo) for cutaneous T-cell lymphoma.
By working with Aslam, the operatives “obtained prescription drugs from an authorized distributor that they would not otherwise have been permitted to purchase, and which they were able to sell at a profit,” according to the indictment.
Both the prosecuting assistant US attorney, Andrew Lievense, and Aslam’s defense lawyer, Daniel Dena, declined to comment for this news organization.
The prosecutor is seeking to recoup the more than $2.5 million Aslam allegedly pocketed, according to the indictment. The press release also noted that an “indictment is only a charge and is not evidence of guilt.”
A version of this article first appeared on Medscape.com.
In late October, a federal grand jury charged a Detroit-area medical oncologist Naveed Aslam, MD, in an indictment for his part in a scheme to illegally sell cancer drugs.
According to the indictment, Aslam acquired and sold more than $17 million in cancer drugs and personally netted more than $2.5 million during the scheme.
The charges against Aslam, filed on October 23 in the US District Court for the Eastern District of Michigan, include 10 counts of illegally selling or trading prescription drugs and one count of conspiring to do so.
“Dr. Aslam’s alleged participation in this scheme not only allowed him to profit unlawfully from the sale of cancer drugs but it also posed a serious threat by potentially placing these medications into the wrong hands,” Cheyvoryea Gibson, special agent in charge of the FBI in Michigan, said in a press release announcing the indictment.
The investigation is being conducted jointly by the FBI, the US Food and Drug Administration (FDA), the US Department of Health and Human Services Office of Inspector General, and Homeland Security Investigations.
The indictment alleges that Aslam was recruited by an unnamed operator of a Michigan corporation that engaged in business as a retail pharmacy and in the wholesale distribution of expensive prescription drugs, largely oncology drugs.
According to the indictment, Aslam and the operator came to an agreement where Aslam would purchase these expensive drugs from an authorized distributor under the false pretense that he was going to prescribe them to patients.
Instead, Aslam allegedly “sold and transferred the prescription drugs” to or through the Michigan business, with involvement from the unnamed operator and a second unnamed individual.
The unnamed individuals “identified customers interested in buying prescription cancer drugs” and “communicated with Dr. Aslam about what cancer drugs were requested,” according to the press release. “Dr. Aslam used his access to certain cancer drugs through his medical practice, Somerset Hematology and Oncology, P.C., to order and purchase the cancer drugs from his supplier.”
The indictment lays out that Aslam allegedly profited from this scheme in several ways, which included charging the Michigan business more than he paid the distributor for the drugs, sharing the profits when the business resold the drugs at a markup, and receiving rebates and discounts from the distributor “based on the amount of qualifying drugs he purchased and resold.”
According to the indictment, the scheme ran from early 2019 to mid-2023 and included four antibody drug conjugates — trastuzumab deruxtecan (Enhertu), enfortumab vedotin (Padcev), tisotumab vedotin (Tivdak), and sacituzumab govitecan (Trodelvy) — and the monoclonal antibody mogamulizumab (Poteligeo) for cutaneous T-cell lymphoma.
By working with Aslam, the operatives “obtained prescription drugs from an authorized distributor that they would not otherwise have been permitted to purchase, and which they were able to sell at a profit,” according to the indictment.
Both the prosecuting assistant US attorney, Andrew Lievense, and Aslam’s defense lawyer, Daniel Dena, declined to comment for this news organization.
The prosecutor is seeking to recoup the more than $2.5 million Aslam allegedly pocketed, according to the indictment. The press release also noted that an “indictment is only a charge and is not evidence of guilt.”
A version of this article first appeared on Medscape.com.
Lymphoma Debate: CAR T Not a Clear Winner
Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.
“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
Targeted Therapies Still Relevant to Advanced FL
Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.
“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible.
Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution.
The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited.
“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”
In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio.
BsAbs Vie With CAR T Cells in Advanced FL
Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both.
There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals.
“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.
“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery.
The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients.
In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment.
“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said.
No Data to Compare BsAbs and CAR T-Cells Directly
Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.
“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.
“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.
For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.
“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.
Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.
Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve.
“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.
Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
A version of this article appeared on Medscape.com.
Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.
“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
Targeted Therapies Still Relevant to Advanced FL
Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.
“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible.
Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution.
The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited.
“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”
In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio.
BsAbs Vie With CAR T Cells in Advanced FL
Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both.
There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals.
“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.
“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery.
The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients.
In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment.
“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said.
No Data to Compare BsAbs and CAR T-Cells Directly
Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.
“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.
“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.
For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.
“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.
Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.
Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve.
“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.
Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
A version of this article appeared on Medscape.com.
Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.
“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
Targeted Therapies Still Relevant to Advanced FL
Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.
“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible.
Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution.
The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited.
“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”
In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio.
BsAbs Vie With CAR T Cells in Advanced FL
Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both.
There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals.
“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.
“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery.
The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients.
In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment.
“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said.
No Data to Compare BsAbs and CAR T-Cells Directly
Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.
“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.
“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.
For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.
“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.
Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.
Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve.
“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.
Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
A version of this article appeared on Medscape.com.
Expert Updates Therapy for Waldenström Macroglobulinemia
Most importantly, determining the mutational status of patients with WM has become a first or early step in guiding first- and second-line therapies, according to Edward A. Stadtmauer, MD, professor of medicine, University of Pennsylvania, Philadelphia.
Presenting at the 2024 Lymphoma, Leukemia & Myeloma Congress in New York City, Stadtmauer discussed how MYD88 and CXCR4 gene mutations influence his therapeutic choices.
While delivering the Bruce Waterfall Memorial Lecture, funded by the International WM Foundation, he explained that the vast majority of patients with WM have a MYD88 mutation that is highly sensitive to Bruton tyrosine kinase (BTK) inhibitors.
Due to greater specificity on the BTK target, which has implications for safety and efficacy, the first-generation BTK inhibitor ibrutinib has been largely supplanted by next generation drugs such as zanubrutinib.
Deep Responses in WM Remain Elusive
The support for next-generation BTK inhibitors over ibrutinib; bendamustine plus rituximab (BR); or cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is, in his opinion, “a superior toxicity profile, high response rates, and prolonged response.” However, he conceded that the weaknesses of this approach include a low chance of a deep remission and the need for continuous therapy.
On account of these limitations, he typically favors the alkylating agent bendamustine plus the anti-CD20 rituximab over BTK inhibitors in the absence of MYD88 mutations. This once standard approach has become less commonly used in the era of BTK inhibitors, but it is also highly effective, is generally administered in a time-limited regimen, and may be more likely to push patients into a deep remission.
A similar rationale might be considered for CyBorD, but Stadtmauer believes that BR provides a higher rate of PFS with a lower risk for neuropathy, although he admitted this opinion is based on cross-study comparisons, not comparative trials.
While efforts to develop therapies capable of producing a deep response “should not be abandoned,” particularly with the T-cell engager therapies on the horizon, he is not convinced that the benefit-to-risk ratio of aggressive therapies is yet warranted in a disease the often progresses slowly.
“I must admit I am still under the philosophy that Waldenström’s is a chronic disease even if we are seeing a growing list of options for relapsed or poorly responding disease, so I am still not pushing patients too aggressively to knock them into a complete remission,” he said.
MYD88 mutations are not unique to WM, an uncommon, slow-growing form of non-Hodgkin lymphoma. They are found in a small proportion of patients with other hematologic disorders, such as marginal zone lymphomas, but Stadtmauer estimated they occur in 90% of patients with WM. They are common enough that they can help with diagnosis.
CXCR4 Mutations Predict Worse Outcomes
The CXCR4 mutation occurs in an estimated 40% of patients with WM. When present, they are associated with worse outcomes, including a faster time to progression and a reduced overall survival, according to Stadtmauer.
The prognostic impact of less common mutations, such as TP53 and TERT or deletions in LYN, are less well characterized, but Stadtmauer said that most mutations associated with WM result in constitutive or continuous activation in BTK, which, in turn drives WM cell proliferation and survival.
The importance of BTK in WM progression is the reason targeted inhibitors have assumed such a key role in first-line treatment, but Stadtmauer cautioned that these drugs, like other therapies, should not be initiated in asymptomatic patients. This has been stated in past and current guidelines.
More accurately, therapy should be held until just prior to symptomatic manifestations of disease, Stadtmauer specified.
For an optimal response, “you want to start therapy about 3 or 4 months before the symptoms begin,” said Stadtmauer characterizing efforts to do so as “the art of medicine.” Starting therapy just prior to symptoms is advantageous, but it involves following patients closely. Any single biomarker might not be enough.
“In an asymptomatic patient, the level of monoclonal IgM is not an indication to start therapy,” he said, citing studies showing no effect on subsequent disease control from treating this biomarker alone.
However, he listed the development of moderate peripheral neuropathy (PN) as an exception. Essentially, anything greater than mild PN is “still bad” in Stadtmauer’s opinion, so treatment is warranted.
The growing number of second-line options relieves some of the concern when patients progress. Stadtmauer said he is now using BR more often in the second-line drug now that he is using BTK inhibitor more in the first line.
The Bcl-2 inhibitor venetoclax is highly effective and is another first- or second-line option even if this agent, like BTK inhibitors, also appears to require continuous dosing, said Stadtmauer, citing a study that showed patients relapsed relatively rapidly when the drug was stopped.
He now thinks of regimens with proteasome inhibitors as third line.
In selected patients who do not tolerate the non-covalent second-generation BTK inhibitors in the first or second line, he said, “I move quickly to the covalent BTKi pirtobrutinib,” based on data suggesting responses that are at least as good but with a better tolerability profile.
T-Cell Engager Data Are Limited
Without spending much time on the T-cell engagers, such as CAR T-cells or bispecific antibodies, Stadtmauer said that the advances he sees on the horizon “are tremendous,” and the “future is bright.” Such approaches could yield deep responses that could extend control or even provide cure, but these are speculations until more patients have been treated and followed long term.
Morton Coleman, MD, director of the Center for Lymphoma and Myeloma at Weill Cornell Medicine and the chairperson of the LLM Congress, called the talk a valuable and practical summary from a knowledgeable source. BTK inhibitors have represented a major evolution in WM management, but Coleman appreciated the underlying concept that treatment still has to be individualized.
“I think one of the most important take home messages is that the characterization of the mutational profile in patients with Waldenström should be considered a standard of care,” Coleman said. Helpful now, the mutational profile is likely to have a more valuable role as treatment is increasingly individualized.
Stadtmauer reported financial relationships with AbbVie, Bristol Myers Squibb, Celgene, Janssen, and Sorrento. Coleman disclosed ties with AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead, Loxo Oncology, Janssen, and Pharmacyclics.
A version of this article appeared on Medscape.com.
Most importantly, determining the mutational status of patients with WM has become a first or early step in guiding first- and second-line therapies, according to Edward A. Stadtmauer, MD, professor of medicine, University of Pennsylvania, Philadelphia.
Presenting at the 2024 Lymphoma, Leukemia & Myeloma Congress in New York City, Stadtmauer discussed how MYD88 and CXCR4 gene mutations influence his therapeutic choices.
While delivering the Bruce Waterfall Memorial Lecture, funded by the International WM Foundation, he explained that the vast majority of patients with WM have a MYD88 mutation that is highly sensitive to Bruton tyrosine kinase (BTK) inhibitors.
Due to greater specificity on the BTK target, which has implications for safety and efficacy, the first-generation BTK inhibitor ibrutinib has been largely supplanted by next generation drugs such as zanubrutinib.
Deep Responses in WM Remain Elusive
The support for next-generation BTK inhibitors over ibrutinib; bendamustine plus rituximab (BR); or cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is, in his opinion, “a superior toxicity profile, high response rates, and prolonged response.” However, he conceded that the weaknesses of this approach include a low chance of a deep remission and the need for continuous therapy.
On account of these limitations, he typically favors the alkylating agent bendamustine plus the anti-CD20 rituximab over BTK inhibitors in the absence of MYD88 mutations. This once standard approach has become less commonly used in the era of BTK inhibitors, but it is also highly effective, is generally administered in a time-limited regimen, and may be more likely to push patients into a deep remission.
A similar rationale might be considered for CyBorD, but Stadtmauer believes that BR provides a higher rate of PFS with a lower risk for neuropathy, although he admitted this opinion is based on cross-study comparisons, not comparative trials.
While efforts to develop therapies capable of producing a deep response “should not be abandoned,” particularly with the T-cell engager therapies on the horizon, he is not convinced that the benefit-to-risk ratio of aggressive therapies is yet warranted in a disease the often progresses slowly.
“I must admit I am still under the philosophy that Waldenström’s is a chronic disease even if we are seeing a growing list of options for relapsed or poorly responding disease, so I am still not pushing patients too aggressively to knock them into a complete remission,” he said.
MYD88 mutations are not unique to WM, an uncommon, slow-growing form of non-Hodgkin lymphoma. They are found in a small proportion of patients with other hematologic disorders, such as marginal zone lymphomas, but Stadtmauer estimated they occur in 90% of patients with WM. They are common enough that they can help with diagnosis.
CXCR4 Mutations Predict Worse Outcomes
The CXCR4 mutation occurs in an estimated 40% of patients with WM. When present, they are associated with worse outcomes, including a faster time to progression and a reduced overall survival, according to Stadtmauer.
The prognostic impact of less common mutations, such as TP53 and TERT or deletions in LYN, are less well characterized, but Stadtmauer said that most mutations associated with WM result in constitutive or continuous activation in BTK, which, in turn drives WM cell proliferation and survival.
The importance of BTK in WM progression is the reason targeted inhibitors have assumed such a key role in first-line treatment, but Stadtmauer cautioned that these drugs, like other therapies, should not be initiated in asymptomatic patients. This has been stated in past and current guidelines.
More accurately, therapy should be held until just prior to symptomatic manifestations of disease, Stadtmauer specified.
For an optimal response, “you want to start therapy about 3 or 4 months before the symptoms begin,” said Stadtmauer characterizing efforts to do so as “the art of medicine.” Starting therapy just prior to symptoms is advantageous, but it involves following patients closely. Any single biomarker might not be enough.
“In an asymptomatic patient, the level of monoclonal IgM is not an indication to start therapy,” he said, citing studies showing no effect on subsequent disease control from treating this biomarker alone.
However, he listed the development of moderate peripheral neuropathy (PN) as an exception. Essentially, anything greater than mild PN is “still bad” in Stadtmauer’s opinion, so treatment is warranted.
The growing number of second-line options relieves some of the concern when patients progress. Stadtmauer said he is now using BR more often in the second-line drug now that he is using BTK inhibitor more in the first line.
The Bcl-2 inhibitor venetoclax is highly effective and is another first- or second-line option even if this agent, like BTK inhibitors, also appears to require continuous dosing, said Stadtmauer, citing a study that showed patients relapsed relatively rapidly when the drug was stopped.
He now thinks of regimens with proteasome inhibitors as third line.
In selected patients who do not tolerate the non-covalent second-generation BTK inhibitors in the first or second line, he said, “I move quickly to the covalent BTKi pirtobrutinib,” based on data suggesting responses that are at least as good but with a better tolerability profile.
T-Cell Engager Data Are Limited
Without spending much time on the T-cell engagers, such as CAR T-cells or bispecific antibodies, Stadtmauer said that the advances he sees on the horizon “are tremendous,” and the “future is bright.” Such approaches could yield deep responses that could extend control or even provide cure, but these are speculations until more patients have been treated and followed long term.
Morton Coleman, MD, director of the Center for Lymphoma and Myeloma at Weill Cornell Medicine and the chairperson of the LLM Congress, called the talk a valuable and practical summary from a knowledgeable source. BTK inhibitors have represented a major evolution in WM management, but Coleman appreciated the underlying concept that treatment still has to be individualized.
“I think one of the most important take home messages is that the characterization of the mutational profile in patients with Waldenström should be considered a standard of care,” Coleman said. Helpful now, the mutational profile is likely to have a more valuable role as treatment is increasingly individualized.
Stadtmauer reported financial relationships with AbbVie, Bristol Myers Squibb, Celgene, Janssen, and Sorrento. Coleman disclosed ties with AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead, Loxo Oncology, Janssen, and Pharmacyclics.
A version of this article appeared on Medscape.com.
Most importantly, determining the mutational status of patients with WM has become a first or early step in guiding first- and second-line therapies, according to Edward A. Stadtmauer, MD, professor of medicine, University of Pennsylvania, Philadelphia.
Presenting at the 2024 Lymphoma, Leukemia & Myeloma Congress in New York City, Stadtmauer discussed how MYD88 and CXCR4 gene mutations influence his therapeutic choices.
While delivering the Bruce Waterfall Memorial Lecture, funded by the International WM Foundation, he explained that the vast majority of patients with WM have a MYD88 mutation that is highly sensitive to Bruton tyrosine kinase (BTK) inhibitors.
Due to greater specificity on the BTK target, which has implications for safety and efficacy, the first-generation BTK inhibitor ibrutinib has been largely supplanted by next generation drugs such as zanubrutinib.
Deep Responses in WM Remain Elusive
The support for next-generation BTK inhibitors over ibrutinib; bendamustine plus rituximab (BR); or cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is, in his opinion, “a superior toxicity profile, high response rates, and prolonged response.” However, he conceded that the weaknesses of this approach include a low chance of a deep remission and the need for continuous therapy.
On account of these limitations, he typically favors the alkylating agent bendamustine plus the anti-CD20 rituximab over BTK inhibitors in the absence of MYD88 mutations. This once standard approach has become less commonly used in the era of BTK inhibitors, but it is also highly effective, is generally administered in a time-limited regimen, and may be more likely to push patients into a deep remission.
A similar rationale might be considered for CyBorD, but Stadtmauer believes that BR provides a higher rate of PFS with a lower risk for neuropathy, although he admitted this opinion is based on cross-study comparisons, not comparative trials.
While efforts to develop therapies capable of producing a deep response “should not be abandoned,” particularly with the T-cell engager therapies on the horizon, he is not convinced that the benefit-to-risk ratio of aggressive therapies is yet warranted in a disease the often progresses slowly.
“I must admit I am still under the philosophy that Waldenström’s is a chronic disease even if we are seeing a growing list of options for relapsed or poorly responding disease, so I am still not pushing patients too aggressively to knock them into a complete remission,” he said.
MYD88 mutations are not unique to WM, an uncommon, slow-growing form of non-Hodgkin lymphoma. They are found in a small proportion of patients with other hematologic disorders, such as marginal zone lymphomas, but Stadtmauer estimated they occur in 90% of patients with WM. They are common enough that they can help with diagnosis.
CXCR4 Mutations Predict Worse Outcomes
The CXCR4 mutation occurs in an estimated 40% of patients with WM. When present, they are associated with worse outcomes, including a faster time to progression and a reduced overall survival, according to Stadtmauer.
The prognostic impact of less common mutations, such as TP53 and TERT or deletions in LYN, are less well characterized, but Stadtmauer said that most mutations associated with WM result in constitutive or continuous activation in BTK, which, in turn drives WM cell proliferation and survival.
The importance of BTK in WM progression is the reason targeted inhibitors have assumed such a key role in first-line treatment, but Stadtmauer cautioned that these drugs, like other therapies, should not be initiated in asymptomatic patients. This has been stated in past and current guidelines.
More accurately, therapy should be held until just prior to symptomatic manifestations of disease, Stadtmauer specified.
For an optimal response, “you want to start therapy about 3 or 4 months before the symptoms begin,” said Stadtmauer characterizing efforts to do so as “the art of medicine.” Starting therapy just prior to symptoms is advantageous, but it involves following patients closely. Any single biomarker might not be enough.
“In an asymptomatic patient, the level of monoclonal IgM is not an indication to start therapy,” he said, citing studies showing no effect on subsequent disease control from treating this biomarker alone.
However, he listed the development of moderate peripheral neuropathy (PN) as an exception. Essentially, anything greater than mild PN is “still bad” in Stadtmauer’s opinion, so treatment is warranted.
The growing number of second-line options relieves some of the concern when patients progress. Stadtmauer said he is now using BR more often in the second-line drug now that he is using BTK inhibitor more in the first line.
The Bcl-2 inhibitor venetoclax is highly effective and is another first- or second-line option even if this agent, like BTK inhibitors, also appears to require continuous dosing, said Stadtmauer, citing a study that showed patients relapsed relatively rapidly when the drug was stopped.
He now thinks of regimens with proteasome inhibitors as third line.
In selected patients who do not tolerate the non-covalent second-generation BTK inhibitors in the first or second line, he said, “I move quickly to the covalent BTKi pirtobrutinib,” based on data suggesting responses that are at least as good but with a better tolerability profile.
T-Cell Engager Data Are Limited
Without spending much time on the T-cell engagers, such as CAR T-cells or bispecific antibodies, Stadtmauer said that the advances he sees on the horizon “are tremendous,” and the “future is bright.” Such approaches could yield deep responses that could extend control or even provide cure, but these are speculations until more patients have been treated and followed long term.
Morton Coleman, MD, director of the Center for Lymphoma and Myeloma at Weill Cornell Medicine and the chairperson of the LLM Congress, called the talk a valuable and practical summary from a knowledgeable source. BTK inhibitors have represented a major evolution in WM management, but Coleman appreciated the underlying concept that treatment still has to be individualized.
“I think one of the most important take home messages is that the characterization of the mutational profile in patients with Waldenström should be considered a standard of care,” Coleman said. Helpful now, the mutational profile is likely to have a more valuable role as treatment is increasingly individualized.
Stadtmauer reported financial relationships with AbbVie, Bristol Myers Squibb, Celgene, Janssen, and Sorrento. Coleman disclosed ties with AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead, Loxo Oncology, Janssen, and Pharmacyclics.
A version of this article appeared on Medscape.com.
For Radiation ‘Downwinders,’ Cancer Compensation Is On Hold
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.
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.
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.
Popular Weight Loss Drugs Now for Patients With Cancer?
Demand for new weight loss drugs has surged over the past few years.
Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.
Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression.
While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.
The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects.
The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut.
Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.
“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City.
Why GLP-1s in Cancer?
GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar.
These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer.
Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.
In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.
Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.
Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma.
But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.
Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population.
Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m2 (range, 23-50 kg/m2).
From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy.
In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer.
Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population.
“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.
It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.
Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.
However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound.
As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk).
These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.
Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said
Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions.
Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.
Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer.
“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”
The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer.
But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said.
Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.
A version of this article first appeared on Medscape.com.
Demand for new weight loss drugs has surged over the past few years.
Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.
Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression.
While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.
The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects.
The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut.
Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.
“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City.
Why GLP-1s in Cancer?
GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar.
These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer.
Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.
In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.
Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.
Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma.
But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.
Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population.
Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m2 (range, 23-50 kg/m2).
From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy.
In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer.
Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population.
“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.
It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.
Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.
However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound.
As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk).
These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.
Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said
Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions.
Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.
Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer.
“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”
The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer.
But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said.
Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.
A version of this article first appeared on Medscape.com.
Demand for new weight loss drugs has surged over the past few years.
Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.
Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression.
While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.
The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects.
The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut.
Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.
“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City.
Why GLP-1s in Cancer?
GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar.
These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer.
Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.
In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.
Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.
Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma.
But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.
Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population.
Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m2 (range, 23-50 kg/m2).
From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy.
In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer.
Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population.
“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.
It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.
Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.
However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound.
As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk).
These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.
Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said
Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions.
Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.
Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer.
“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”
The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer.
But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said.
Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.
A version of this article first appeared on Medscape.com.
Does Medicare Advantage Offer Higher-Value Chemotherapy?
TOPLINE:
METHODOLOGY:
- Private Medicare Advantage plans enroll more than half of the Medicare population, but it is unknown if or how the cost restrictions they impose affect chemotherapy, which accounts for a large portion of cancer care costs.
- Researchers conducted a cohort study using national Medicare data from January 2015 to December 2019 to look at Medicare Advantage enrollment and treatment patterns for patients with cancer receiving chemotherapy.
- The study included 96,501 Medicare Advantage enrollees and 206,274 traditional Medicare beneficiaries who initiated chemotherapy between January 2016 and December 2019 (mean age, ~73 years; ~56% women; Hispanic individuals, 15% and 8%; Black individuals, 15% and 8%; and White individuals, 75% and 86%, respectively).
- Resource use and care quality were measured during a 6-month period following chemotherapy initiation, and survival days were measured 18 months after beginning chemotherapy.
- Resource use measures included hospital inpatient services, outpatient care, prescription drugs, hospice services, and chemotherapy services. Quality measures included chemotherapy-related emergency visits and hospital admissions, as well as avoidable emergency visits and preventable hospitalizations.
TAKEAWAY:
- Medicare Advantage plans had lower resource use than traditional Medicare per enrollee with cancer undergoing chemotherapy ($8718 lower; 95% CI, $8343-$9094).
- The lower resource use was largely caused by fewer chemotherapy visits and less expensive chemotherapy per visit in Medicare Advantage plans ($5032 lower; 95% CI, $4772-$5293).
- Medicare Advantage enrollees had 2.5 percentage points fewer chemotherapy-related emergency department visits and 0.7 percentage points fewer chemotherapy-related hospitalizations than traditional Medicare beneficiaries.
- There was no clinically meaningful difference in survival between Medicare Advantage and traditional Medicare beneficiaries during the 18 months following chemotherapy initiation.
IN PRACTICE:
“Our new finding is that MA [Medicare Advantage] plans had lower resource use than TM [traditional Medicare] among enrollees with cancer undergoing chemotherapy — a serious condition managed by specialists and requiring expensive treatments. This suggests that MA’s cost advantages over TM are not limited to conditions for which low-cost primary care management can avoid costly services,” the authors wrote.
SOURCE:
The study was led by Yamini Kalidindi, PhD, McDermott+ Consulting, Washington, DC. It was published online on September 20, 2024, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2024.34707), with a commentary.
LIMITATIONS:
The study’s findings may be affected by unobserved patient characteristics despite the use of inverse-probability weighting. The exclusion of Medicare Advantage enrollees in contracts with incomplete encounter data limits the generalizability of the results. The study does not apply to beneficiaries without Part D drug coverage. Quality measures were limited to those available from claims and encounter data, lacking information on patients’ cancer stage. The 18-month measure of survival might not adequately capture survival differences associated with early-stage cancers. The study did not measure whether patient care followed recommended guidelines.
DISCLOSURES:
Various authors reported grants from the National Institute on Aging, the National Institutes of Health, The Commonwealth Fund, Arnold Ventures, the National Cancer Institute, the Department of Defense, and the National Institute of Health Care Management. Additional disclosures are noted in the original article.
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:
METHODOLOGY:
- Private Medicare Advantage plans enroll more than half of the Medicare population, but it is unknown if or how the cost restrictions they impose affect chemotherapy, which accounts for a large portion of cancer care costs.
- Researchers conducted a cohort study using national Medicare data from January 2015 to December 2019 to look at Medicare Advantage enrollment and treatment patterns for patients with cancer receiving chemotherapy.
- The study included 96,501 Medicare Advantage enrollees and 206,274 traditional Medicare beneficiaries who initiated chemotherapy between January 2016 and December 2019 (mean age, ~73 years; ~56% women; Hispanic individuals, 15% and 8%; Black individuals, 15% and 8%; and White individuals, 75% and 86%, respectively).
- Resource use and care quality were measured during a 6-month period following chemotherapy initiation, and survival days were measured 18 months after beginning chemotherapy.
- Resource use measures included hospital inpatient services, outpatient care, prescription drugs, hospice services, and chemotherapy services. Quality measures included chemotherapy-related emergency visits and hospital admissions, as well as avoidable emergency visits and preventable hospitalizations.
TAKEAWAY:
- Medicare Advantage plans had lower resource use than traditional Medicare per enrollee with cancer undergoing chemotherapy ($8718 lower; 95% CI, $8343-$9094).
- The lower resource use was largely caused by fewer chemotherapy visits and less expensive chemotherapy per visit in Medicare Advantage plans ($5032 lower; 95% CI, $4772-$5293).
- Medicare Advantage enrollees had 2.5 percentage points fewer chemotherapy-related emergency department visits and 0.7 percentage points fewer chemotherapy-related hospitalizations than traditional Medicare beneficiaries.
- There was no clinically meaningful difference in survival between Medicare Advantage and traditional Medicare beneficiaries during the 18 months following chemotherapy initiation.
IN PRACTICE:
“Our new finding is that MA [Medicare Advantage] plans had lower resource use than TM [traditional Medicare] among enrollees with cancer undergoing chemotherapy — a serious condition managed by specialists and requiring expensive treatments. This suggests that MA’s cost advantages over TM are not limited to conditions for which low-cost primary care management can avoid costly services,” the authors wrote.
SOURCE:
The study was led by Yamini Kalidindi, PhD, McDermott+ Consulting, Washington, DC. It was published online on September 20, 2024, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2024.34707), with a commentary.
LIMITATIONS:
The study’s findings may be affected by unobserved patient characteristics despite the use of inverse-probability weighting. The exclusion of Medicare Advantage enrollees in contracts with incomplete encounter data limits the generalizability of the results. The study does not apply to beneficiaries without Part D drug coverage. Quality measures were limited to those available from claims and encounter data, lacking information on patients’ cancer stage. The 18-month measure of survival might not adequately capture survival differences associated with early-stage cancers. The study did not measure whether patient care followed recommended guidelines.
DISCLOSURES:
Various authors reported grants from the National Institute on Aging, the National Institutes of Health, The Commonwealth Fund, Arnold Ventures, the National Cancer Institute, the Department of Defense, and the National Institute of Health Care Management. Additional disclosures are noted in the original article.
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:
METHODOLOGY:
- Private Medicare Advantage plans enroll more than half of the Medicare population, but it is unknown if or how the cost restrictions they impose affect chemotherapy, which accounts for a large portion of cancer care costs.
- Researchers conducted a cohort study using national Medicare data from January 2015 to December 2019 to look at Medicare Advantage enrollment and treatment patterns for patients with cancer receiving chemotherapy.
- The study included 96,501 Medicare Advantage enrollees and 206,274 traditional Medicare beneficiaries who initiated chemotherapy between January 2016 and December 2019 (mean age, ~73 years; ~56% women; Hispanic individuals, 15% and 8%; Black individuals, 15% and 8%; and White individuals, 75% and 86%, respectively).
- Resource use and care quality were measured during a 6-month period following chemotherapy initiation, and survival days were measured 18 months after beginning chemotherapy.
- Resource use measures included hospital inpatient services, outpatient care, prescription drugs, hospice services, and chemotherapy services. Quality measures included chemotherapy-related emergency visits and hospital admissions, as well as avoidable emergency visits and preventable hospitalizations.
TAKEAWAY:
- Medicare Advantage plans had lower resource use than traditional Medicare per enrollee with cancer undergoing chemotherapy ($8718 lower; 95% CI, $8343-$9094).
- The lower resource use was largely caused by fewer chemotherapy visits and less expensive chemotherapy per visit in Medicare Advantage plans ($5032 lower; 95% CI, $4772-$5293).
- Medicare Advantage enrollees had 2.5 percentage points fewer chemotherapy-related emergency department visits and 0.7 percentage points fewer chemotherapy-related hospitalizations than traditional Medicare beneficiaries.
- There was no clinically meaningful difference in survival between Medicare Advantage and traditional Medicare beneficiaries during the 18 months following chemotherapy initiation.
IN PRACTICE:
“Our new finding is that MA [Medicare Advantage] plans had lower resource use than TM [traditional Medicare] among enrollees with cancer undergoing chemotherapy — a serious condition managed by specialists and requiring expensive treatments. This suggests that MA’s cost advantages over TM are not limited to conditions for which low-cost primary care management can avoid costly services,” the authors wrote.
SOURCE:
The study was led by Yamini Kalidindi, PhD, McDermott+ Consulting, Washington, DC. It was published online on September 20, 2024, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2024.34707), with a commentary.
LIMITATIONS:
The study’s findings may be affected by unobserved patient characteristics despite the use of inverse-probability weighting. The exclusion of Medicare Advantage enrollees in contracts with incomplete encounter data limits the generalizability of the results. The study does not apply to beneficiaries without Part D drug coverage. Quality measures were limited to those available from claims and encounter data, lacking information on patients’ cancer stage. The 18-month measure of survival might not adequately capture survival differences associated with early-stage cancers. The study did not measure whether patient care followed recommended guidelines.
DISCLOSURES:
Various authors reported grants from the National Institute on Aging, the National Institutes of Health, The Commonwealth Fund, Arnold Ventures, the National Cancer Institute, the Department of Defense, and the National Institute of Health Care Management. Additional disclosures are noted in the original article.
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.
AACR Cancer Progress Report: Big Strides and Big Gaps
The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted.
One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.
These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
Inside the Report: Big Progress
Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives.
According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.
The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.
“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.”
The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.
“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
The Gaps
Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.
“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.
The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.
Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.
Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.
The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.
Financial toxicity remains prevalent as well.
The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.
For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.
On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
The Path Forward
Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.
“I am excited about what the future holds for cancer research, and especially for patient care,” she said.
However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.
Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.
The AACR report specifically calls on Congress to:
- Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
- Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
- Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
- Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.
By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”
A version of this article first appeared on Medscape.com.
The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted.
One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.
These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
Inside the Report: Big Progress
Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives.
According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.
The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.
“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.”
The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.
“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
The Gaps
Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.
“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.
The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.
Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.
Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.
The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.
Financial toxicity remains prevalent as well.
The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.
For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.
On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
The Path Forward
Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.
“I am excited about what the future holds for cancer research, and especially for patient care,” she said.
However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.
Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.
The AACR report specifically calls on Congress to:
- Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
- Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
- Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
- Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.
By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”
A version of this article first appeared on Medscape.com.
The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted.
One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.
These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
Inside the Report: Big Progress
Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives.
According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.
The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.
“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.”
The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.
“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
The Gaps
Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.
“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.
The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.
Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.
Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.
The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.
Financial toxicity remains prevalent as well.
The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.
For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.
On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
The Path Forward
Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.
“I am excited about what the future holds for cancer research, and especially for patient care,” she said.
However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.
Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.
The AACR report specifically calls on Congress to:
- Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
- Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
- Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
- Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.
By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”
A version of this article first appeared on Medscape.com.
Cancer Risk: Are Pesticides the New Smoking?
Pesticides have transformed modern agriculture by boosting production yields and helping alleviate food insecurity amid rapid global population growth. However, from a public health perspective, exposure to pesticides has been linked to numerous harmful effects, including neurologic disorders like Parkinson’s disease, weakened immune function, and an increased risk for cancer.
thus offering a limited perspective.
A comprehensive assessment of how pesticide use affects cancer risk across a broader population has yet to be conducted.
A recent population-level study aimed to address this gap by evaluating cancer risks in the US population using a model that accounts for pesticide use and adjusts for various factors. The goal was to identify regional disparities in exposure and contribute to the development of public health policies that protect populations from potential harm.
Calculating Cancer Risk
Researchers developed a model using several data sources to estimate the additional cancer risk from agricultural pesticide use. Key data included:
- Pesticide use data from the US Geological Survey in 2019, which covered 69 agricultural pesticides across 3143 counties
- Cancer incidence rates per 100,000 people, which were collected between 2015 and 2019 by the National Institutes of Health and the Centers for Disease Control and Prevention; these data covered various cancers, including bladder, colorectal, leukemia, lung, non-Hodgkin lymphoma, and pancreatic cancers
- Covariates, including smoking prevalence, the Social Vulnerability Index, agricultural land use, and total US population in 2019
Pesticide use profile patterns were developed using latent class analysis, a statistical method used to identify homogeneous subgroups within a heterogeneous population. A generalized linear model then estimated how these pesticide use patterns and the covariates affected cancer incidence.
The model highlighted regions with the highest and lowest “additional” cancer risks linked to pesticide exposure, calculating the estimated increase in cancer cases per year that resulted from variations in agricultural pesticide use.
Midwest Most Affected
While this model doesn’t establish causality or assess individual risk, it reveals regional trends in the association between pesticide use patterns and cancer incidence from a population-based perspective.
The Midwest, known for its high corn production, emerged as the region most affected by pesticide use. Compared with regions with the lowest risk, the Midwest faced an additional 154,541 cancer cases annually across all types. For colorectal and pancreatic cancers, the yearly increases were 20,927 and 3835 cases, respectively. Similar trends were observed for leukemia and non-Hodgkin lymphoma.
Pesticides vs Smoking
The researchers also estimated the additional cancer risk related to smoking, using the same model. They found that pesticides contributed to a higher risk for cancer than smoking in several cases.
The most significant difference was observed with non-Hodgkin lymphoma, where pesticides were linked to 154.1% more cases than smoking. For all cancers combined, as well as bladder cancer and leukemia, the increases were moderate: 18.7%, 19.3%, and 21.0%, respectively.
This result highlights the importance of considering pesticide exposure alongside smoking when studying cancer risks.
Expanding Scope of Research
Some limitations of this study should be noted. Certain counties lacked complete data, and there was heterogeneity in the size and population of the counties studied. The research also did not account for seasonal and migrant workers, who are likely to be heavily exposed. In addition, the data used in the study were not independently validated, and they could not be used to assess individual risk.
The effect of pesticides on human health is a vast and critical field of research, often focusing on a limited range of pesticides or specific cancers. This study stands out by taking a broader, more holistic approach, aiming to highlight regional inequalities and identify less-studied pesticides that could be future research priorities.
Given the significant public health impact, the authors encouraged the authorities to share these findings with the most vulnerable communities to raise awareness.
This story was translated from JIM 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.
Pesticides have transformed modern agriculture by boosting production yields and helping alleviate food insecurity amid rapid global population growth. However, from a public health perspective, exposure to pesticides has been linked to numerous harmful effects, including neurologic disorders like Parkinson’s disease, weakened immune function, and an increased risk for cancer.
thus offering a limited perspective.
A comprehensive assessment of how pesticide use affects cancer risk across a broader population has yet to be conducted.
A recent population-level study aimed to address this gap by evaluating cancer risks in the US population using a model that accounts for pesticide use and adjusts for various factors. The goal was to identify regional disparities in exposure and contribute to the development of public health policies that protect populations from potential harm.
Calculating Cancer Risk
Researchers developed a model using several data sources to estimate the additional cancer risk from agricultural pesticide use. Key data included:
- Pesticide use data from the US Geological Survey in 2019, which covered 69 agricultural pesticides across 3143 counties
- Cancer incidence rates per 100,000 people, which were collected between 2015 and 2019 by the National Institutes of Health and the Centers for Disease Control and Prevention; these data covered various cancers, including bladder, colorectal, leukemia, lung, non-Hodgkin lymphoma, and pancreatic cancers
- Covariates, including smoking prevalence, the Social Vulnerability Index, agricultural land use, and total US population in 2019
Pesticide use profile patterns were developed using latent class analysis, a statistical method used to identify homogeneous subgroups within a heterogeneous population. A generalized linear model then estimated how these pesticide use patterns and the covariates affected cancer incidence.
The model highlighted regions with the highest and lowest “additional” cancer risks linked to pesticide exposure, calculating the estimated increase in cancer cases per year that resulted from variations in agricultural pesticide use.
Midwest Most Affected
While this model doesn’t establish causality or assess individual risk, it reveals regional trends in the association between pesticide use patterns and cancer incidence from a population-based perspective.
The Midwest, known for its high corn production, emerged as the region most affected by pesticide use. Compared with regions with the lowest risk, the Midwest faced an additional 154,541 cancer cases annually across all types. For colorectal and pancreatic cancers, the yearly increases were 20,927 and 3835 cases, respectively. Similar trends were observed for leukemia and non-Hodgkin lymphoma.
Pesticides vs Smoking
The researchers also estimated the additional cancer risk related to smoking, using the same model. They found that pesticides contributed to a higher risk for cancer than smoking in several cases.
The most significant difference was observed with non-Hodgkin lymphoma, where pesticides were linked to 154.1% more cases than smoking. For all cancers combined, as well as bladder cancer and leukemia, the increases were moderate: 18.7%, 19.3%, and 21.0%, respectively.
This result highlights the importance of considering pesticide exposure alongside smoking when studying cancer risks.
Expanding Scope of Research
Some limitations of this study should be noted. Certain counties lacked complete data, and there was heterogeneity in the size and population of the counties studied. The research also did not account for seasonal and migrant workers, who are likely to be heavily exposed. In addition, the data used in the study were not independently validated, and they could not be used to assess individual risk.
The effect of pesticides on human health is a vast and critical field of research, often focusing on a limited range of pesticides or specific cancers. This study stands out by taking a broader, more holistic approach, aiming to highlight regional inequalities and identify less-studied pesticides that could be future research priorities.
Given the significant public health impact, the authors encouraged the authorities to share these findings with the most vulnerable communities to raise awareness.
This story was translated from JIM 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.
Pesticides have transformed modern agriculture by boosting production yields and helping alleviate food insecurity amid rapid global population growth. However, from a public health perspective, exposure to pesticides has been linked to numerous harmful effects, including neurologic disorders like Parkinson’s disease, weakened immune function, and an increased risk for cancer.
thus offering a limited perspective.
A comprehensive assessment of how pesticide use affects cancer risk across a broader population has yet to be conducted.
A recent population-level study aimed to address this gap by evaluating cancer risks in the US population using a model that accounts for pesticide use and adjusts for various factors. The goal was to identify regional disparities in exposure and contribute to the development of public health policies that protect populations from potential harm.
Calculating Cancer Risk
Researchers developed a model using several data sources to estimate the additional cancer risk from agricultural pesticide use. Key data included:
- Pesticide use data from the US Geological Survey in 2019, which covered 69 agricultural pesticides across 3143 counties
- Cancer incidence rates per 100,000 people, which were collected between 2015 and 2019 by the National Institutes of Health and the Centers for Disease Control and Prevention; these data covered various cancers, including bladder, colorectal, leukemia, lung, non-Hodgkin lymphoma, and pancreatic cancers
- Covariates, including smoking prevalence, the Social Vulnerability Index, agricultural land use, and total US population in 2019
Pesticide use profile patterns were developed using latent class analysis, a statistical method used to identify homogeneous subgroups within a heterogeneous population. A generalized linear model then estimated how these pesticide use patterns and the covariates affected cancer incidence.
The model highlighted regions with the highest and lowest “additional” cancer risks linked to pesticide exposure, calculating the estimated increase in cancer cases per year that resulted from variations in agricultural pesticide use.
Midwest Most Affected
While this model doesn’t establish causality or assess individual risk, it reveals regional trends in the association between pesticide use patterns and cancer incidence from a population-based perspective.
The Midwest, known for its high corn production, emerged as the region most affected by pesticide use. Compared with regions with the lowest risk, the Midwest faced an additional 154,541 cancer cases annually across all types. For colorectal and pancreatic cancers, the yearly increases were 20,927 and 3835 cases, respectively. Similar trends were observed for leukemia and non-Hodgkin lymphoma.
Pesticides vs Smoking
The researchers also estimated the additional cancer risk related to smoking, using the same model. They found that pesticides contributed to a higher risk for cancer than smoking in several cases.
The most significant difference was observed with non-Hodgkin lymphoma, where pesticides were linked to 154.1% more cases than smoking. For all cancers combined, as well as bladder cancer and leukemia, the increases were moderate: 18.7%, 19.3%, and 21.0%, respectively.
This result highlights the importance of considering pesticide exposure alongside smoking when studying cancer risks.
Expanding Scope of Research
Some limitations of this study should be noted. Certain counties lacked complete data, and there was heterogeneity in the size and population of the counties studied. The research also did not account for seasonal and migrant workers, who are likely to be heavily exposed. In addition, the data used in the study were not independently validated, and they could not be used to assess individual risk.
The effect of pesticides on human health is a vast and critical field of research, often focusing on a limited range of pesticides or specific cancers. This study stands out by taking a broader, more holistic approach, aiming to highlight regional inequalities and identify less-studied pesticides that could be future research priorities.
Given the significant public health impact, the authors encouraged the authorities to share these findings with the most vulnerable communities to raise awareness.
This story was translated from JIM 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.
Do Clonal Hematopoiesis and Mosaic Chromosomal Alterations Increase Solid Tumor Risk?
Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.
These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
How This Study Differs From Others of Breast Cancer Risk Factors
“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.
In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.
But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.
“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”
In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?
To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.
In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.
More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.
The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.
“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.
“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.
“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.
Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
How Do Findings Compare With Those of the UK Biobank Study?
CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.
In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.
“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.
As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.
Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).
The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.
The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.
She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
Why Do Results Differ Between These Types of Studies?
Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.
“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.
“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.
Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?
“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”
Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.
“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
Future research and therapeutic development
Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.
“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.
Available data support both possibilities.
On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.
When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”
The presence of a causal association could be promising from a therapeutic standpoint.
“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.
Yet earlier intervention may still hold promise, according to experts.
“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.
The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.
A version of this article first appeared on Medscape.com.
Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.
These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
How This Study Differs From Others of Breast Cancer Risk Factors
“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.
In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.
But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.
“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”
In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?
To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.
In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.
More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.
The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.
“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.
“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.
“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.
Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
How Do Findings Compare With Those of the UK Biobank Study?
CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.
In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.
“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.
As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.
Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).
The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.
The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.
She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
Why Do Results Differ Between These Types of Studies?
Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.
“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.
“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.
Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?
“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”
Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.
“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
Future research and therapeutic development
Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.
“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.
Available data support both possibilities.
On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.
When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”
The presence of a causal association could be promising from a therapeutic standpoint.
“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.
Yet earlier intervention may still hold promise, according to experts.
“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.
The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.
A version of this article first appeared on Medscape.com.
Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.
These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
How This Study Differs From Others of Breast Cancer Risk Factors
“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.
In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.
But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.
“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”
In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?
To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.
In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.
More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.
The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.
“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.
“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.
“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.
Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
How Do Findings Compare With Those of the UK Biobank Study?
CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.
In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.
“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.
As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.
Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).
The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.
The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.
She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
Why Do Results Differ Between These Types of Studies?
Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.
“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.
“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.
Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?
“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”
Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.
“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
Future research and therapeutic development
Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.
“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.
Available data support both possibilities.
On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.
When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”
The presence of a causal association could be promising from a therapeutic standpoint.
“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.
Yet earlier intervention may still hold promise, according to experts.
“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.
The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.
A version of this article first appeared on Medscape.com.
FROM CANCER