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Outpatient CAR T: Safe, Effective, Accessible
In one recent study, an industry-funded phase 2 trial, researchers found similar outcomes from outpatient and inpatient CAR T-cell therapy for relapsed/refractory large B-cell lymphoma with lisocabtagene maraleucel (Breyanzi).
Another recent study reported that outpatient treatment of B cell non-Hodgkin lymphoma with tisagenlecleucel (Kymriah) had similar efficacy to inpatient treatment. Meanwhile, a 2023 review of CAR T-cell therapy in various settings found similar outcomes in outpatient and inpatient treatment.
“The future of CAR T-cell therapy lies in balancing safety with accessibility,” said Rayne Rouce, MD, a pediatric oncologist at Texas Children’s Cancer Center in Houston, Texas, in an interview. “Expanding CAR T-cell therapy beyond large medical centers is a critical next step.”
Great Outcomes, Low Access
Since 2017, the FDA has approved six CAR T-cell therapies, which target cancer by harnessing the power of a patient’s own T cells. As an Oregon Health & Sciences University/Knight Cancer Center website explains, T cells are removed from the patient’s body, “genetically modified to make the chimeric antigen receptor, or CAR, [which] protein binds to specific proteins on the surface of cancer cells.”
Modified cells are grown and then infused back into the body, where they “multiply and may be able to destroy all the cancer cells.”
As Rouce puts it, “CAR T-cells have revolutionized the treatment of relapsed or refractory blood cancers.” One or more of the therapies have been approved to treat types of lymphoblastic leukemia, B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma.
A 2023 review of clinical trial data reported complete response rates of 40%-54% in aggressive B-cell lymphoma, 67% in mantle cell lymphoma, and 69%-74% in indolent B cell lymphoma.
“Commercialization of CAR T-cell therapy brought hope that access would expand beyond the major academic medical centers with the highly specialized infrastructure and advanced laboratories required to manufacture and ultimately treat patients,” Rouce said. “However, it quickly became clear that patients who are underinsured or uninsured — or who live outside the network of the well-resourced institutions that house these therapies — are still unable to access these potentially life-saving therapies.”
A 2024 report estimated the cost of CAR T-cell therapy as $700,000-$1 million and said only a small percentage of those who could benefit from the treatment actually get it. For example, an estimated 10,000 patients with diffuse large B-cell lymphoma alone could benefit from CAR T therapy annually, but a survey of 200 US healthcare centers in 2021 found that 1900 procedures were performed overall for all indications.
Distance to Treatment Is a Major Obstacle
Even if patients have insurance plans willing to cover CAR T-cell therapy, they may not be able get care. While more than 150 US centers are certified to administer the therapy, “distance to major medical centers with CAR T capabilities is a major obstacle,” Yuliya Linhares, MD, chief of lymphoma at Miami Cancer Institute in Miami, Florida, said in an interview.
“I have had patients who chose to not proceed with CAR T therapy due to inability to travel the distance to the medical center for pre-CAR T appointments and assessments and a lack of caretakers who are available to stay nearby,” Linhares said.
Indeed, the challenges facing patients in rural and underserved urban areas can be overwhelming, Hoda Badr, PhD, professor of medicine at Baylor College of Medicine in Houston, Texas, said in an interview.
“They must take time off work, arrange accommodations near treatment sites, and manage travel costs, all of which strain limited financial resources. The inability to afford these additional expenses can lead to delays in receiving care or patients forgoing the treatment altogether,” Badr said. She added that “the psychological and social burden of being away from family and community support systems during treatment can intensify the stress of an already difficult situation.”
A statistic tells the story of the urban/community divide. CAR T-cell therapy administration at academic centers after leukapheresis — the separation and collection of white blood cells — is reported to be at around 90%, while it’s only 47% in community-based practices that have to refer patients elsewhere, Linhares noted.
Researchers Explore CAR T-Cell Therapy in the Community
Linhares is lead author of the phase 2 trial that explored administration of lisocabtagene maraleucel in 82 patients with relapsed/refractory large B-cell lymphoma. The findings were published Sept. 30 in Blood Advances.
The OUTREACH trial, funded by Juno/Bristol-Myers Squibb, treated patients in the third line and beyond at community medical centers (outpatient-monitored, 70%; inpatient-monitored, 30%). The trial didn’t require facilities to be certified by the Foundation for the Accreditation of Cellular Therapy (FACT); all had to be non-tertiary cancer centers that weren’t associated with a university. In order to administer therapy on the outpatient basis, the centers had to have phase 1 or hematopoietic stem cell transplant capabilities.
As Linhares explained, 72% of participating centers hadn’t provided CAR T-cell therapy before, and 44% did not have FACT accreditation. “About 32% of patients received CAR T at CAR T naive sites, while 70% of patients received CAR T as outpatients. Investigators had to decide whether patients qualified for the outpatient observation or had to be admitted for the inpatient observation,” she noted.
Community Outcomes Were Comparable to Major Trial
As for the results, grade 3 or higher adverse events occurred at a similar frequency among outpatients and inpatients at 74% and 76%, Linhares said. There were no grade 5 adverse events, and 25% of patients treated as outpatients were never hospitalized.
Response rates were similar to those in the major TRANSCEND trial with the objective response rates rate of 80% and complete response rates of 54%.
“Overall,” Linhares said, “our study demonstrated that with the availability of standard operating procedures, specially trained staff and a multidisciplinary team trained in CAR T toxicity management, inpatient and outpatient CAR T administration is feasible at specialized community medical centers.”
In 2023, another study examined patients with B-cell non-Hodgkin lymphoma who were treated on an outpatient basis with tisagenlecleucel. Researchers reported that outpatient therapy was “feasible and associated with similar efficacy outcomes as inpatient treatment.”
And a 2023 systematic literature review identified 11 studies that reported outpatient vs inpatient outcomes in CAR T-cell therapy and found “comparable response rates (80-82% in outpatient and 72-80% in inpatient).” Costs were cheaper in the outpatient setting.
Research findings like these are good news, Baylor College of Medicine’s Badr said. “Outpatient administration could help to scale the availability of this therapy to a broader range of healthcare settings, including those serving underserved populations. Findings indicate promising safety profiles, which is encouraging for expanding access.”
Not Every Patient Can Tolerate Outpatient Care
Linhares noted that the patients who received outpatient care in the lisocabtagene maraleucel study were in better shape than those in the inpatient group. Those selected for inpatient care had “higher disease risk characteristics, including high grade B cell lymphoma histology, higher disease burden, and having received bridging therapy. This points to the fact that the investigators properly selected patients who were at a higher risk of complications for inpatient observation. Additionally, some patients stayed as inpatient due to social factors, which increases length of stay independently of disease characteristics.”
Specifically, reasons for inpatient monitoring were disease characteristics (48%) including tumor burden and risk of adverse events; psychosocial factors (32%) including lack of caregiver support or transportation; COVID-19 precautions (8%); pre-infusion adverse events (8%) of fever and vasovagal reaction; and principal investigator decision (4%) due to limited hospital experience with CAR T-cell therapy.
Texas Children’s Cancer Center’s Rouce said “certain patients, particularly those with higher risk for complications or those who require intensive monitoring, may not be suited for outpatient CAR T-cell therapy. This may be due to other comorbidities or baseline factors known to predispose to CAR T-related toxicities. However, evidence-based risk mitigation algorithms may still allow closely monitored outpatient treatment, with recognition that hospital admission for incipient side effects may be necessary.”
What’s Next for Access to Therapy?
Rouce noted that her institution, like many others, is offering CAR T-cell therapy on an outpatient basis. “Additionally, continued scientific innovation, such as immediately available, off-the-shelf cell therapies and inducible safety switches, will ultimately improve access,” she said.
Linhares noted a recent advance and highlighted research that’s now in progress. “CAR Ts now have an indication as a second-line therapy in relapsed/refractory large B-cell lymphoma, and there are ongoing clinical trials that will potentially move CAR Ts into the first line,” she said. “Some trials are exploring allogeneic, readily available off-the-shelf CAR T for the treatment of minimal residual disease positive large B-cell lymphoma after completion of first-line therapy.”
These potential advances “are increasing the need for CAR T-capable medical centers,” Linhares noted. “More and more medical centers with expert hematology teams are becoming CAR T-certified, with more patients having access to CAR T.”
Still, she said, “I don’t think access is nearly as good as it should be. Many patients in rural areas are still unable to get this life-saving treatment. “However, “it is very possible that other novel targeted therapies, such as bispecific antibodies, will be used in place of CAR T in areas with poor CAR T access. Bispecific antibody efficacy in various B cell lymphoma histologies are being currently explored.”
Rouce discloses relationships with Novartis and Pfizer. Linhares reports ties with Kyowa Kirin, AbbVie, ADC, BeiGene, Genentech, Gilead, GlaxoSmithKline, Seagen, and TG. Badr has no disclosures.
A version of this article appeared on Medscape.com.
In one recent study, an industry-funded phase 2 trial, researchers found similar outcomes from outpatient and inpatient CAR T-cell therapy for relapsed/refractory large B-cell lymphoma with lisocabtagene maraleucel (Breyanzi).
Another recent study reported that outpatient treatment of B cell non-Hodgkin lymphoma with tisagenlecleucel (Kymriah) had similar efficacy to inpatient treatment. Meanwhile, a 2023 review of CAR T-cell therapy in various settings found similar outcomes in outpatient and inpatient treatment.
“The future of CAR T-cell therapy lies in balancing safety with accessibility,” said Rayne Rouce, MD, a pediatric oncologist at Texas Children’s Cancer Center in Houston, Texas, in an interview. “Expanding CAR T-cell therapy beyond large medical centers is a critical next step.”
Great Outcomes, Low Access
Since 2017, the FDA has approved six CAR T-cell therapies, which target cancer by harnessing the power of a patient’s own T cells. As an Oregon Health & Sciences University/Knight Cancer Center website explains, T cells are removed from the patient’s body, “genetically modified to make the chimeric antigen receptor, or CAR, [which] protein binds to specific proteins on the surface of cancer cells.”
Modified cells are grown and then infused back into the body, where they “multiply and may be able to destroy all the cancer cells.”
As Rouce puts it, “CAR T-cells have revolutionized the treatment of relapsed or refractory blood cancers.” One or more of the therapies have been approved to treat types of lymphoblastic leukemia, B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma.
A 2023 review of clinical trial data reported complete response rates of 40%-54% in aggressive B-cell lymphoma, 67% in mantle cell lymphoma, and 69%-74% in indolent B cell lymphoma.
“Commercialization of CAR T-cell therapy brought hope that access would expand beyond the major academic medical centers with the highly specialized infrastructure and advanced laboratories required to manufacture and ultimately treat patients,” Rouce said. “However, it quickly became clear that patients who are underinsured or uninsured — or who live outside the network of the well-resourced institutions that house these therapies — are still unable to access these potentially life-saving therapies.”
A 2024 report estimated the cost of CAR T-cell therapy as $700,000-$1 million and said only a small percentage of those who could benefit from the treatment actually get it. For example, an estimated 10,000 patients with diffuse large B-cell lymphoma alone could benefit from CAR T therapy annually, but a survey of 200 US healthcare centers in 2021 found that 1900 procedures were performed overall for all indications.
Distance to Treatment Is a Major Obstacle
Even if patients have insurance plans willing to cover CAR T-cell therapy, they may not be able get care. While more than 150 US centers are certified to administer the therapy, “distance to major medical centers with CAR T capabilities is a major obstacle,” Yuliya Linhares, MD, chief of lymphoma at Miami Cancer Institute in Miami, Florida, said in an interview.
“I have had patients who chose to not proceed with CAR T therapy due to inability to travel the distance to the medical center for pre-CAR T appointments and assessments and a lack of caretakers who are available to stay nearby,” Linhares said.
Indeed, the challenges facing patients in rural and underserved urban areas can be overwhelming, Hoda Badr, PhD, professor of medicine at Baylor College of Medicine in Houston, Texas, said in an interview.
“They must take time off work, arrange accommodations near treatment sites, and manage travel costs, all of which strain limited financial resources. The inability to afford these additional expenses can lead to delays in receiving care or patients forgoing the treatment altogether,” Badr said. She added that “the psychological and social burden of being away from family and community support systems during treatment can intensify the stress of an already difficult situation.”
A statistic tells the story of the urban/community divide. CAR T-cell therapy administration at academic centers after leukapheresis — the separation and collection of white blood cells — is reported to be at around 90%, while it’s only 47% in community-based practices that have to refer patients elsewhere, Linhares noted.
Researchers Explore CAR T-Cell Therapy in the Community
Linhares is lead author of the phase 2 trial that explored administration of lisocabtagene maraleucel in 82 patients with relapsed/refractory large B-cell lymphoma. The findings were published Sept. 30 in Blood Advances.
The OUTREACH trial, funded by Juno/Bristol-Myers Squibb, treated patients in the third line and beyond at community medical centers (outpatient-monitored, 70%; inpatient-monitored, 30%). The trial didn’t require facilities to be certified by the Foundation for the Accreditation of Cellular Therapy (FACT); all had to be non-tertiary cancer centers that weren’t associated with a university. In order to administer therapy on the outpatient basis, the centers had to have phase 1 or hematopoietic stem cell transplant capabilities.
As Linhares explained, 72% of participating centers hadn’t provided CAR T-cell therapy before, and 44% did not have FACT accreditation. “About 32% of patients received CAR T at CAR T naive sites, while 70% of patients received CAR T as outpatients. Investigators had to decide whether patients qualified for the outpatient observation or had to be admitted for the inpatient observation,” she noted.
Community Outcomes Were Comparable to Major Trial
As for the results, grade 3 or higher adverse events occurred at a similar frequency among outpatients and inpatients at 74% and 76%, Linhares said. There were no grade 5 adverse events, and 25% of patients treated as outpatients were never hospitalized.
Response rates were similar to those in the major TRANSCEND trial with the objective response rates rate of 80% and complete response rates of 54%.
“Overall,” Linhares said, “our study demonstrated that with the availability of standard operating procedures, specially trained staff and a multidisciplinary team trained in CAR T toxicity management, inpatient and outpatient CAR T administration is feasible at specialized community medical centers.”
In 2023, another study examined patients with B-cell non-Hodgkin lymphoma who were treated on an outpatient basis with tisagenlecleucel. Researchers reported that outpatient therapy was “feasible and associated with similar efficacy outcomes as inpatient treatment.”
And a 2023 systematic literature review identified 11 studies that reported outpatient vs inpatient outcomes in CAR T-cell therapy and found “comparable response rates (80-82% in outpatient and 72-80% in inpatient).” Costs were cheaper in the outpatient setting.
Research findings like these are good news, Baylor College of Medicine’s Badr said. “Outpatient administration could help to scale the availability of this therapy to a broader range of healthcare settings, including those serving underserved populations. Findings indicate promising safety profiles, which is encouraging for expanding access.”
Not Every Patient Can Tolerate Outpatient Care
Linhares noted that the patients who received outpatient care in the lisocabtagene maraleucel study were in better shape than those in the inpatient group. Those selected for inpatient care had “higher disease risk characteristics, including high grade B cell lymphoma histology, higher disease burden, and having received bridging therapy. This points to the fact that the investigators properly selected patients who were at a higher risk of complications for inpatient observation. Additionally, some patients stayed as inpatient due to social factors, which increases length of stay independently of disease characteristics.”
Specifically, reasons for inpatient monitoring were disease characteristics (48%) including tumor burden and risk of adverse events; psychosocial factors (32%) including lack of caregiver support or transportation; COVID-19 precautions (8%); pre-infusion adverse events (8%) of fever and vasovagal reaction; and principal investigator decision (4%) due to limited hospital experience with CAR T-cell therapy.
Texas Children’s Cancer Center’s Rouce said “certain patients, particularly those with higher risk for complications or those who require intensive monitoring, may not be suited for outpatient CAR T-cell therapy. This may be due to other comorbidities or baseline factors known to predispose to CAR T-related toxicities. However, evidence-based risk mitigation algorithms may still allow closely monitored outpatient treatment, with recognition that hospital admission for incipient side effects may be necessary.”
What’s Next for Access to Therapy?
Rouce noted that her institution, like many others, is offering CAR T-cell therapy on an outpatient basis. “Additionally, continued scientific innovation, such as immediately available, off-the-shelf cell therapies and inducible safety switches, will ultimately improve access,” she said.
Linhares noted a recent advance and highlighted research that’s now in progress. “CAR Ts now have an indication as a second-line therapy in relapsed/refractory large B-cell lymphoma, and there are ongoing clinical trials that will potentially move CAR Ts into the first line,” she said. “Some trials are exploring allogeneic, readily available off-the-shelf CAR T for the treatment of minimal residual disease positive large B-cell lymphoma after completion of first-line therapy.”
These potential advances “are increasing the need for CAR T-capable medical centers,” Linhares noted. “More and more medical centers with expert hematology teams are becoming CAR T-certified, with more patients having access to CAR T.”
Still, she said, “I don’t think access is nearly as good as it should be. Many patients in rural areas are still unable to get this life-saving treatment. “However, “it is very possible that other novel targeted therapies, such as bispecific antibodies, will be used in place of CAR T in areas with poor CAR T access. Bispecific antibody efficacy in various B cell lymphoma histologies are being currently explored.”
Rouce discloses relationships with Novartis and Pfizer. Linhares reports ties with Kyowa Kirin, AbbVie, ADC, BeiGene, Genentech, Gilead, GlaxoSmithKline, Seagen, and TG. Badr has no disclosures.
A version of this article appeared on Medscape.com.
In one recent study, an industry-funded phase 2 trial, researchers found similar outcomes from outpatient and inpatient CAR T-cell therapy for relapsed/refractory large B-cell lymphoma with lisocabtagene maraleucel (Breyanzi).
Another recent study reported that outpatient treatment of B cell non-Hodgkin lymphoma with tisagenlecleucel (Kymriah) had similar efficacy to inpatient treatment. Meanwhile, a 2023 review of CAR T-cell therapy in various settings found similar outcomes in outpatient and inpatient treatment.
“The future of CAR T-cell therapy lies in balancing safety with accessibility,” said Rayne Rouce, MD, a pediatric oncologist at Texas Children’s Cancer Center in Houston, Texas, in an interview. “Expanding CAR T-cell therapy beyond large medical centers is a critical next step.”
Great Outcomes, Low Access
Since 2017, the FDA has approved six CAR T-cell therapies, which target cancer by harnessing the power of a patient’s own T cells. As an Oregon Health & Sciences University/Knight Cancer Center website explains, T cells are removed from the patient’s body, “genetically modified to make the chimeric antigen receptor, or CAR, [which] protein binds to specific proteins on the surface of cancer cells.”
Modified cells are grown and then infused back into the body, where they “multiply and may be able to destroy all the cancer cells.”
As Rouce puts it, “CAR T-cells have revolutionized the treatment of relapsed or refractory blood cancers.” One or more of the therapies have been approved to treat types of lymphoblastic leukemia, B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma.
A 2023 review of clinical trial data reported complete response rates of 40%-54% in aggressive B-cell lymphoma, 67% in mantle cell lymphoma, and 69%-74% in indolent B cell lymphoma.
“Commercialization of CAR T-cell therapy brought hope that access would expand beyond the major academic medical centers with the highly specialized infrastructure and advanced laboratories required to manufacture and ultimately treat patients,” Rouce said. “However, it quickly became clear that patients who are underinsured or uninsured — or who live outside the network of the well-resourced institutions that house these therapies — are still unable to access these potentially life-saving therapies.”
A 2024 report estimated the cost of CAR T-cell therapy as $700,000-$1 million and said only a small percentage of those who could benefit from the treatment actually get it. For example, an estimated 10,000 patients with diffuse large B-cell lymphoma alone could benefit from CAR T therapy annually, but a survey of 200 US healthcare centers in 2021 found that 1900 procedures were performed overall for all indications.
Distance to Treatment Is a Major Obstacle
Even if patients have insurance plans willing to cover CAR T-cell therapy, they may not be able get care. While more than 150 US centers are certified to administer the therapy, “distance to major medical centers with CAR T capabilities is a major obstacle,” Yuliya Linhares, MD, chief of lymphoma at Miami Cancer Institute in Miami, Florida, said in an interview.
“I have had patients who chose to not proceed with CAR T therapy due to inability to travel the distance to the medical center for pre-CAR T appointments and assessments and a lack of caretakers who are available to stay nearby,” Linhares said.
Indeed, the challenges facing patients in rural and underserved urban areas can be overwhelming, Hoda Badr, PhD, professor of medicine at Baylor College of Medicine in Houston, Texas, said in an interview.
“They must take time off work, arrange accommodations near treatment sites, and manage travel costs, all of which strain limited financial resources. The inability to afford these additional expenses can lead to delays in receiving care or patients forgoing the treatment altogether,” Badr said. She added that “the psychological and social burden of being away from family and community support systems during treatment can intensify the stress of an already difficult situation.”
A statistic tells the story of the urban/community divide. CAR T-cell therapy administration at academic centers after leukapheresis — the separation and collection of white blood cells — is reported to be at around 90%, while it’s only 47% in community-based practices that have to refer patients elsewhere, Linhares noted.
Researchers Explore CAR T-Cell Therapy in the Community
Linhares is lead author of the phase 2 trial that explored administration of lisocabtagene maraleucel in 82 patients with relapsed/refractory large B-cell lymphoma. The findings were published Sept. 30 in Blood Advances.
The OUTREACH trial, funded by Juno/Bristol-Myers Squibb, treated patients in the third line and beyond at community medical centers (outpatient-monitored, 70%; inpatient-monitored, 30%). The trial didn’t require facilities to be certified by the Foundation for the Accreditation of Cellular Therapy (FACT); all had to be non-tertiary cancer centers that weren’t associated with a university. In order to administer therapy on the outpatient basis, the centers had to have phase 1 or hematopoietic stem cell transplant capabilities.
As Linhares explained, 72% of participating centers hadn’t provided CAR T-cell therapy before, and 44% did not have FACT accreditation. “About 32% of patients received CAR T at CAR T naive sites, while 70% of patients received CAR T as outpatients. Investigators had to decide whether patients qualified for the outpatient observation or had to be admitted for the inpatient observation,” she noted.
Community Outcomes Were Comparable to Major Trial
As for the results, grade 3 or higher adverse events occurred at a similar frequency among outpatients and inpatients at 74% and 76%, Linhares said. There were no grade 5 adverse events, and 25% of patients treated as outpatients were never hospitalized.
Response rates were similar to those in the major TRANSCEND trial with the objective response rates rate of 80% and complete response rates of 54%.
“Overall,” Linhares said, “our study demonstrated that with the availability of standard operating procedures, specially trained staff and a multidisciplinary team trained in CAR T toxicity management, inpatient and outpatient CAR T administration is feasible at specialized community medical centers.”
In 2023, another study examined patients with B-cell non-Hodgkin lymphoma who were treated on an outpatient basis with tisagenlecleucel. Researchers reported that outpatient therapy was “feasible and associated with similar efficacy outcomes as inpatient treatment.”
And a 2023 systematic literature review identified 11 studies that reported outpatient vs inpatient outcomes in CAR T-cell therapy and found “comparable response rates (80-82% in outpatient and 72-80% in inpatient).” Costs were cheaper in the outpatient setting.
Research findings like these are good news, Baylor College of Medicine’s Badr said. “Outpatient administration could help to scale the availability of this therapy to a broader range of healthcare settings, including those serving underserved populations. Findings indicate promising safety profiles, which is encouraging for expanding access.”
Not Every Patient Can Tolerate Outpatient Care
Linhares noted that the patients who received outpatient care in the lisocabtagene maraleucel study were in better shape than those in the inpatient group. Those selected for inpatient care had “higher disease risk characteristics, including high grade B cell lymphoma histology, higher disease burden, and having received bridging therapy. This points to the fact that the investigators properly selected patients who were at a higher risk of complications for inpatient observation. Additionally, some patients stayed as inpatient due to social factors, which increases length of stay independently of disease characteristics.”
Specifically, reasons for inpatient monitoring were disease characteristics (48%) including tumor burden and risk of adverse events; psychosocial factors (32%) including lack of caregiver support or transportation; COVID-19 precautions (8%); pre-infusion adverse events (8%) of fever and vasovagal reaction; and principal investigator decision (4%) due to limited hospital experience with CAR T-cell therapy.
Texas Children’s Cancer Center’s Rouce said “certain patients, particularly those with higher risk for complications or those who require intensive monitoring, may not be suited for outpatient CAR T-cell therapy. This may be due to other comorbidities or baseline factors known to predispose to CAR T-related toxicities. However, evidence-based risk mitigation algorithms may still allow closely monitored outpatient treatment, with recognition that hospital admission for incipient side effects may be necessary.”
What’s Next for Access to Therapy?
Rouce noted that her institution, like many others, is offering CAR T-cell therapy on an outpatient basis. “Additionally, continued scientific innovation, such as immediately available, off-the-shelf cell therapies and inducible safety switches, will ultimately improve access,” she said.
Linhares noted a recent advance and highlighted research that’s now in progress. “CAR Ts now have an indication as a second-line therapy in relapsed/refractory large B-cell lymphoma, and there are ongoing clinical trials that will potentially move CAR Ts into the first line,” she said. “Some trials are exploring allogeneic, readily available off-the-shelf CAR T for the treatment of minimal residual disease positive large B-cell lymphoma after completion of first-line therapy.”
These potential advances “are increasing the need for CAR T-capable medical centers,” Linhares noted. “More and more medical centers with expert hematology teams are becoming CAR T-certified, with more patients having access to CAR T.”
Still, she said, “I don’t think access is nearly as good as it should be. Many patients in rural areas are still unable to get this life-saving treatment. “However, “it is very possible that other novel targeted therapies, such as bispecific antibodies, will be used in place of CAR T in areas with poor CAR T access. Bispecific antibody efficacy in various B cell lymphoma histologies are being currently explored.”
Rouce discloses relationships with Novartis and Pfizer. Linhares reports ties with Kyowa Kirin, AbbVie, ADC, BeiGene, Genentech, Gilead, GlaxoSmithKline, Seagen, and TG. Badr has no disclosures.
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.
Treatment Options in MCL: What Are the Best Practices?
In the frontline setting, findings suggest that regimens should differ significantly on the basis of whether patients are older or younger, whereas more data are needed to understand whether treatment can overcome poor prognoses in patients with TP53 mutations, lymphoma specialist Nina Wagner-Johnston, MD, of Johns Hopkins University School of Medicine, Baltimore, said in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) 2024 in Houston, Texas.
On the relapsed/refractory front, patients need better options after treatment with Bruton tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T-cell therapy, Krish Patel, MD, a lymphoma specialist with Swedish Cancer Institute in Seattle, said in an adjoining presentation. Fortunately, he said, some treatments are showing early promise.
Here’s a closer look at the presentations by Dr. Wagner-Johnston and Dr. Patel.
Frontline MCL: Age Helps Determine Best Approach
“For older and less fit patients, the standard approach has typically been bendamustine (Bendeka, Treanda) and rituximab (Rituxan), and the median progression-free survival is about 4 years, with overall survival not reached at a median 5 years of follow-up,” Dr. Wagner-Johnston said.
Low doses of the chemotherapy drug cytarabine have been added to the bendamustine-rituximab regimen, with encouraging results, she said. “Certainly there’s more toxicity associated even with lower doses, but those data look fairly promising.”
For younger and fit patients, “the standard of care approach has been to administer intensive chemoimmunotherapy that contains high-dose cytarabine, and then that’s typically followed with an autologous stem cell transplant,” she said. A 2016 study reported median progression-free survival of 8.5 years and median overall survival of 12.7 years.
Now, second-generation Bruton tyrosine kinase inhibitors “look very promising” in the frontline setting, Dr. Wagner-Johnston said.
The road has been rocky, however. The SHINE trial of more than 500 patients aged over 65 found that adding ibrutinib to bendamustine-rituximab improved progression-free survival. “However, progression-free survival did not [connect] to an overall survival benefit, and that’s likely due to the toxicity seen with ibrutinib,” she said.
“It’s not surprising to many of you that ibrutinib has been removed from the FDA label for mantle cell lymphoma,” she said. However, “second-generation [Bruton tyrosine kinase inhibitors] are known to be associated with less toxicity and potentially increased potency.”
What about Bruton tyrosine kinase inhibitors in younger and fitter patients? The TRIANGLE trial demonstrated their benefit, Dr. Wagner-Johnston said, linking ibrutinib to improvement in progression-free survival.
However, “it’s really too early to evaluate the statistical significance for overall survival.” And while the study looks at therapy without stem cell transplant, she believes it’s too early to know whether that’s a good option.
Dr. Wagner-Johnston tackled another topic: Can Bruton tyrosine kinase inhibitors overcome the poor prognosis seen with MCL with TP53 mutation? For now, the limitations of research makes it “hard to know,” she said, although early results of the BOVen trial are promising.
Relapsed/Refractory MCL: Better Options Are Still Needed
In his presentation, Dr. Patel spoke about therapy in patients with MCL and relapsed/refractory disease. “We know that outcomes for patients who progress on covalent [Bruton tyrosine kinase inhibitors] is really dismal,” he said. “This has been shown by multiple groups now across the globe.”
Noncovalent Bruton tyrosine kinase inhibitors are now an option, he noted. “We do understand that they work for some patients, and it can be quite useful, but even noncovalent [Bruton tyrosine kinase inhibitors] themselves are susceptible to resistance mutations. We’ve seen that in the [chronic lymphocytic leukemia] world.”
Dr. Patel asked the audience, “Why not just give everybody CAR T-cells, post-[Bruton tyrosine kinase inhibitors]? You get a CAR T-cell! You get a CAR T-cell! Everybody gets one.”
However, he noted, “Unfortunately, mantle cell lymphoma patients experience the worst high-grade toxicity when receiving CD19[-targeted] CAR T-cells.”
Are there better options? At the moment, “really, really early data” suggest benefits from molecular glues and degraders, novel inhibitors, antibody-drug conjugates, novel CAR T-cells, and bispecific antibodies, Dr. Patel said.
“All of these tools are in clinical trials, and hopefully some of them will help,” he said.
Disclosures were not provided. Dr. Wagner-Johnston recently disclosed advisory committee/board of directors’ relationships with ADC Therapeutics, Regeneron, Calibr, and Verastem. Dr. Patel recently disclosed ties with a long list of pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, Merck, and others.
A version of this article first appeared on Medscape.com.
In the frontline setting, findings suggest that regimens should differ significantly on the basis of whether patients are older or younger, whereas more data are needed to understand whether treatment can overcome poor prognoses in patients with TP53 mutations, lymphoma specialist Nina Wagner-Johnston, MD, of Johns Hopkins University School of Medicine, Baltimore, said in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) 2024 in Houston, Texas.
On the relapsed/refractory front, patients need better options after treatment with Bruton tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T-cell therapy, Krish Patel, MD, a lymphoma specialist with Swedish Cancer Institute in Seattle, said in an adjoining presentation. Fortunately, he said, some treatments are showing early promise.
Here’s a closer look at the presentations by Dr. Wagner-Johnston and Dr. Patel.
Frontline MCL: Age Helps Determine Best Approach
“For older and less fit patients, the standard approach has typically been bendamustine (Bendeka, Treanda) and rituximab (Rituxan), and the median progression-free survival is about 4 years, with overall survival not reached at a median 5 years of follow-up,” Dr. Wagner-Johnston said.
Low doses of the chemotherapy drug cytarabine have been added to the bendamustine-rituximab regimen, with encouraging results, she said. “Certainly there’s more toxicity associated even with lower doses, but those data look fairly promising.”
For younger and fit patients, “the standard of care approach has been to administer intensive chemoimmunotherapy that contains high-dose cytarabine, and then that’s typically followed with an autologous stem cell transplant,” she said. A 2016 study reported median progression-free survival of 8.5 years and median overall survival of 12.7 years.
Now, second-generation Bruton tyrosine kinase inhibitors “look very promising” in the frontline setting, Dr. Wagner-Johnston said.
The road has been rocky, however. The SHINE trial of more than 500 patients aged over 65 found that adding ibrutinib to bendamustine-rituximab improved progression-free survival. “However, progression-free survival did not [connect] to an overall survival benefit, and that’s likely due to the toxicity seen with ibrutinib,” she said.
“It’s not surprising to many of you that ibrutinib has been removed from the FDA label for mantle cell lymphoma,” she said. However, “second-generation [Bruton tyrosine kinase inhibitors] are known to be associated with less toxicity and potentially increased potency.”
What about Bruton tyrosine kinase inhibitors in younger and fitter patients? The TRIANGLE trial demonstrated their benefit, Dr. Wagner-Johnston said, linking ibrutinib to improvement in progression-free survival.
However, “it’s really too early to evaluate the statistical significance for overall survival.” And while the study looks at therapy without stem cell transplant, she believes it’s too early to know whether that’s a good option.
Dr. Wagner-Johnston tackled another topic: Can Bruton tyrosine kinase inhibitors overcome the poor prognosis seen with MCL with TP53 mutation? For now, the limitations of research makes it “hard to know,” she said, although early results of the BOVen trial are promising.
Relapsed/Refractory MCL: Better Options Are Still Needed
In his presentation, Dr. Patel spoke about therapy in patients with MCL and relapsed/refractory disease. “We know that outcomes for patients who progress on covalent [Bruton tyrosine kinase inhibitors] is really dismal,” he said. “This has been shown by multiple groups now across the globe.”
Noncovalent Bruton tyrosine kinase inhibitors are now an option, he noted. “We do understand that they work for some patients, and it can be quite useful, but even noncovalent [Bruton tyrosine kinase inhibitors] themselves are susceptible to resistance mutations. We’ve seen that in the [chronic lymphocytic leukemia] world.”
Dr. Patel asked the audience, “Why not just give everybody CAR T-cells, post-[Bruton tyrosine kinase inhibitors]? You get a CAR T-cell! You get a CAR T-cell! Everybody gets one.”
However, he noted, “Unfortunately, mantle cell lymphoma patients experience the worst high-grade toxicity when receiving CD19[-targeted] CAR T-cells.”
Are there better options? At the moment, “really, really early data” suggest benefits from molecular glues and degraders, novel inhibitors, antibody-drug conjugates, novel CAR T-cells, and bispecific antibodies, Dr. Patel said.
“All of these tools are in clinical trials, and hopefully some of them will help,” he said.
Disclosures were not provided. Dr. Wagner-Johnston recently disclosed advisory committee/board of directors’ relationships with ADC Therapeutics, Regeneron, Calibr, and Verastem. Dr. Patel recently disclosed ties with a long list of pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, Merck, and others.
A version of this article first appeared on Medscape.com.
In the frontline setting, findings suggest that regimens should differ significantly on the basis of whether patients are older or younger, whereas more data are needed to understand whether treatment can overcome poor prognoses in patients with TP53 mutations, lymphoma specialist Nina Wagner-Johnston, MD, of Johns Hopkins University School of Medicine, Baltimore, said in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) 2024 in Houston, Texas.
On the relapsed/refractory front, patients need better options after treatment with Bruton tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T-cell therapy, Krish Patel, MD, a lymphoma specialist with Swedish Cancer Institute in Seattle, said in an adjoining presentation. Fortunately, he said, some treatments are showing early promise.
Here’s a closer look at the presentations by Dr. Wagner-Johnston and Dr. Patel.
Frontline MCL: Age Helps Determine Best Approach
“For older and less fit patients, the standard approach has typically been bendamustine (Bendeka, Treanda) and rituximab (Rituxan), and the median progression-free survival is about 4 years, with overall survival not reached at a median 5 years of follow-up,” Dr. Wagner-Johnston said.
Low doses of the chemotherapy drug cytarabine have been added to the bendamustine-rituximab regimen, with encouraging results, she said. “Certainly there’s more toxicity associated even with lower doses, but those data look fairly promising.”
For younger and fit patients, “the standard of care approach has been to administer intensive chemoimmunotherapy that contains high-dose cytarabine, and then that’s typically followed with an autologous stem cell transplant,” she said. A 2016 study reported median progression-free survival of 8.5 years and median overall survival of 12.7 years.
Now, second-generation Bruton tyrosine kinase inhibitors “look very promising” in the frontline setting, Dr. Wagner-Johnston said.
The road has been rocky, however. The SHINE trial of more than 500 patients aged over 65 found that adding ibrutinib to bendamustine-rituximab improved progression-free survival. “However, progression-free survival did not [connect] to an overall survival benefit, and that’s likely due to the toxicity seen with ibrutinib,” she said.
“It’s not surprising to many of you that ibrutinib has been removed from the FDA label for mantle cell lymphoma,” she said. However, “second-generation [Bruton tyrosine kinase inhibitors] are known to be associated with less toxicity and potentially increased potency.”
What about Bruton tyrosine kinase inhibitors in younger and fitter patients? The TRIANGLE trial demonstrated their benefit, Dr. Wagner-Johnston said, linking ibrutinib to improvement in progression-free survival.
However, “it’s really too early to evaluate the statistical significance for overall survival.” And while the study looks at therapy without stem cell transplant, she believes it’s too early to know whether that’s a good option.
Dr. Wagner-Johnston tackled another topic: Can Bruton tyrosine kinase inhibitors overcome the poor prognosis seen with MCL with TP53 mutation? For now, the limitations of research makes it “hard to know,” she said, although early results of the BOVen trial are promising.
Relapsed/Refractory MCL: Better Options Are Still Needed
In his presentation, Dr. Patel spoke about therapy in patients with MCL and relapsed/refractory disease. “We know that outcomes for patients who progress on covalent [Bruton tyrosine kinase inhibitors] is really dismal,” he said. “This has been shown by multiple groups now across the globe.”
Noncovalent Bruton tyrosine kinase inhibitors are now an option, he noted. “We do understand that they work for some patients, and it can be quite useful, but even noncovalent [Bruton tyrosine kinase inhibitors] themselves are susceptible to resistance mutations. We’ve seen that in the [chronic lymphocytic leukemia] world.”
Dr. Patel asked the audience, “Why not just give everybody CAR T-cells, post-[Bruton tyrosine kinase inhibitors]? You get a CAR T-cell! You get a CAR T-cell! Everybody gets one.”
However, he noted, “Unfortunately, mantle cell lymphoma patients experience the worst high-grade toxicity when receiving CD19[-targeted] CAR T-cells.”
Are there better options? At the moment, “really, really early data” suggest benefits from molecular glues and degraders, novel inhibitors, antibody-drug conjugates, novel CAR T-cells, and bispecific antibodies, Dr. Patel said.
“All of these tools are in clinical trials, and hopefully some of them will help,” he said.
Disclosures were not provided. Dr. Wagner-Johnston recently disclosed advisory committee/board of directors’ relationships with ADC Therapeutics, Regeneron, Calibr, and Verastem. Dr. Patel recently disclosed ties with a long list of pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Janssen, Merck, and others.
A version of this article first appeared on Medscape.com.
FROM SOHO 2024
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
Cancer Cases, Deaths in Men Predicted to Surge by 2050
TOPLINE:
— with substantial disparities in cancer cases and deaths by age and region of the world, a recent analysis found.
METHODOLOGY:
- Overall, men have higher cancer incidence and mortality rates, which can be largely attributed to a higher prevalence of modifiable risk factors such as smoking, alcohol consumption, and occupational carcinogens, as well as the underuse of cancer prevention, screening, and treatment services.
- To assess the burden of cancer in men of different ages and from different regions of the world, researchers analyzed data from the 2022 Global Cancer Observatory (GLOBOCAN), which provides national-level estimates for cancer cases and deaths.
- Study outcomes included the incidence, mortality, and prevalence of cancer among men in 2022, along with projections for 2050. Estimates were stratified by several factors, including age; region; and Human Development Index (HDI), a composite score for health, education, and standard of living.
- Researchers also calculated mortality-to-incidence ratios (MIRs) for various cancer types, where higher values indicate worse survival.
TAKEAWAY:
- The researchers reported an estimated 10.3 million cancer cases and 5.4 million deaths globally in 2022, with almost two thirds of cases and deaths occurring in men aged 65 years or older.
- By 2050, cancer cases and deaths were projected to increase by 84.3% (to 19 million) and 93.2% (to 10.5 million), respectively. The increase from 2022 to 2050 was more than twofold higher for older men and countries with low and medium HDI.
- In 2022, the estimated global cancer MIR among men was nearly 55%, with variations by cancer types, age, and HDI. The MIR was lowest for thyroid cancer (7.6%) and highest for pancreatic cancer (90.9%); among World Health Organization regions, Africa had the highest MIR (72.6%), while the Americas had the lowest MIR (39.1%); countries with the lowest HDI had the highest MIR (73.5% vs 41.1% for very high HDI).
- Lung cancer was the leading cause for cases and deaths in 2022 and was projected to remain the leading cause in 2050.
IN PRACTICE:
“Disparities in cancer incidence and mortality among men were observed across age groups, countries/territories, and HDI in 2022, with these disparities projected to widen further by 2050,” according to the authors, who called for efforts to “reduce disparities in cancer burden and ensure equity in cancer prevention and care for men across the globe.”
SOURCE:
The study, led by Habtamu Mellie Bizuayehu, PhD, School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, Australia, was published online in Cancer.
LIMITATIONS:
The findings may be influenced by the quality of GLOBOCAN data. Interpretation should be cautious as MIR may not fully reflect cancer outcome inequalities. The study did not include other measures of cancer burden, such as years of life lost or years lived with disability, which were unavailable from the data source.
DISCLOSURES:
The authors did not disclose any funding information. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
— with substantial disparities in cancer cases and deaths by age and region of the world, a recent analysis found.
METHODOLOGY:
- Overall, men have higher cancer incidence and mortality rates, which can be largely attributed to a higher prevalence of modifiable risk factors such as smoking, alcohol consumption, and occupational carcinogens, as well as the underuse of cancer prevention, screening, and treatment services.
- To assess the burden of cancer in men of different ages and from different regions of the world, researchers analyzed data from the 2022 Global Cancer Observatory (GLOBOCAN), which provides national-level estimates for cancer cases and deaths.
- Study outcomes included the incidence, mortality, and prevalence of cancer among men in 2022, along with projections for 2050. Estimates were stratified by several factors, including age; region; and Human Development Index (HDI), a composite score for health, education, and standard of living.
- Researchers also calculated mortality-to-incidence ratios (MIRs) for various cancer types, where higher values indicate worse survival.
TAKEAWAY:
- The researchers reported an estimated 10.3 million cancer cases and 5.4 million deaths globally in 2022, with almost two thirds of cases and deaths occurring in men aged 65 years or older.
- By 2050, cancer cases and deaths were projected to increase by 84.3% (to 19 million) and 93.2% (to 10.5 million), respectively. The increase from 2022 to 2050 was more than twofold higher for older men and countries with low and medium HDI.
- In 2022, the estimated global cancer MIR among men was nearly 55%, with variations by cancer types, age, and HDI. The MIR was lowest for thyroid cancer (7.6%) and highest for pancreatic cancer (90.9%); among World Health Organization regions, Africa had the highest MIR (72.6%), while the Americas had the lowest MIR (39.1%); countries with the lowest HDI had the highest MIR (73.5% vs 41.1% for very high HDI).
- Lung cancer was the leading cause for cases and deaths in 2022 and was projected to remain the leading cause in 2050.
IN PRACTICE:
“Disparities in cancer incidence and mortality among men were observed across age groups, countries/territories, and HDI in 2022, with these disparities projected to widen further by 2050,” according to the authors, who called for efforts to “reduce disparities in cancer burden and ensure equity in cancer prevention and care for men across the globe.”
SOURCE:
The study, led by Habtamu Mellie Bizuayehu, PhD, School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, Australia, was published online in Cancer.
LIMITATIONS:
The findings may be influenced by the quality of GLOBOCAN data. Interpretation should be cautious as MIR may not fully reflect cancer outcome inequalities. The study did not include other measures of cancer burden, such as years of life lost or years lived with disability, which were unavailable from the data source.
DISCLOSURES:
The authors did not disclose any funding information. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
— with substantial disparities in cancer cases and deaths by age and region of the world, a recent analysis found.
METHODOLOGY:
- Overall, men have higher cancer incidence and mortality rates, which can be largely attributed to a higher prevalence of modifiable risk factors such as smoking, alcohol consumption, and occupational carcinogens, as well as the underuse of cancer prevention, screening, and treatment services.
- To assess the burden of cancer in men of different ages and from different regions of the world, researchers analyzed data from the 2022 Global Cancer Observatory (GLOBOCAN), which provides national-level estimates for cancer cases and deaths.
- Study outcomes included the incidence, mortality, and prevalence of cancer among men in 2022, along with projections for 2050. Estimates were stratified by several factors, including age; region; and Human Development Index (HDI), a composite score for health, education, and standard of living.
- Researchers also calculated mortality-to-incidence ratios (MIRs) for various cancer types, where higher values indicate worse survival.
TAKEAWAY:
- The researchers reported an estimated 10.3 million cancer cases and 5.4 million deaths globally in 2022, with almost two thirds of cases and deaths occurring in men aged 65 years or older.
- By 2050, cancer cases and deaths were projected to increase by 84.3% (to 19 million) and 93.2% (to 10.5 million), respectively. The increase from 2022 to 2050 was more than twofold higher for older men and countries with low and medium HDI.
- In 2022, the estimated global cancer MIR among men was nearly 55%, with variations by cancer types, age, and HDI. The MIR was lowest for thyroid cancer (7.6%) and highest for pancreatic cancer (90.9%); among World Health Organization regions, Africa had the highest MIR (72.6%), while the Americas had the lowest MIR (39.1%); countries with the lowest HDI had the highest MIR (73.5% vs 41.1% for very high HDI).
- Lung cancer was the leading cause for cases and deaths in 2022 and was projected to remain the leading cause in 2050.
IN PRACTICE:
“Disparities in cancer incidence and mortality among men were observed across age groups, countries/territories, and HDI in 2022, with these disparities projected to widen further by 2050,” according to the authors, who called for efforts to “reduce disparities in cancer burden and ensure equity in cancer prevention and care for men across the globe.”
SOURCE:
The study, led by Habtamu Mellie Bizuayehu, PhD, School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, Australia, was published online in Cancer.
LIMITATIONS:
The findings may be influenced by the quality of GLOBOCAN data. Interpretation should be cautious as MIR may not fully reflect cancer outcome inequalities. The study did not include other measures of cancer burden, such as years of life lost or years lived with disability, which were unavailable from the data source.
DISCLOSURES:
The authors did not disclose any funding information. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Cancer Treatment 101: A Primer for Non-Oncologists
The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.
I’m speaking in generalities, understanding that each cancer and each patient is unique.
Chemotherapy
Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.
Careful, compassionate communication between patient and physician is key. Goals and expectations must be clearly understood.
Organized chemotherapeutic efforts are further categorized as first line, second line, and third line.
First-line treatment. The initial round of recommended chemotherapy for a specific cancer. It is typically considered the most effective treatment for that type and stage of cancer on the basis of current research and clinical trials.
Second-line treatment. This is the treatment used if the first-line chemotherapy doesn’t work as desired. Reasons to switch to second-line chemo include:
- Lack of response (the tumor failed to shrink).
- Progression (the cancer may have grown or spread further).
- Adverse side effects were too severe to continue.
The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.
Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:
- New or different chemotherapy drugs compared with prior lines.
- Surgery to debulk the tumor.
- Radiation for symptom control.
- Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
- Immunotherapy: agents that help the body’s immune system fight cancer cells.
- Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.
The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.
It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.
Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
Interventions to Consider Earlier
In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:
- Molecular testing.
- Palliation.
- Clinical trials.
- Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.
I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.
Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:
- Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
- Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
- Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.
Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.
Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.
Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.
Specific situations where discussing palliative care might be appropriate are:
- Soon after a cancer diagnosis.
- If the patient experiences significant side effects from cancer treatment.
- When considering different treatment options, palliative care can complement those treatments.
- In advanced stages of cancer, to focus on comfort and quality of life.
Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.
In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.
Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.
These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.
Read more about these leading innovations:
SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment
Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working
PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment
Using Live Cells from Patients to Find the Right Cancer Drug
Other innovative therapies under investigation could even be agnostic to cancer type:
Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?
High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells
All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions
Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.
Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.
I’m speaking in generalities, understanding that each cancer and each patient is unique.
Chemotherapy
Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.
Careful, compassionate communication between patient and physician is key. Goals and expectations must be clearly understood.
Organized chemotherapeutic efforts are further categorized as first line, second line, and third line.
First-line treatment. The initial round of recommended chemotherapy for a specific cancer. It is typically considered the most effective treatment for that type and stage of cancer on the basis of current research and clinical trials.
Second-line treatment. This is the treatment used if the first-line chemotherapy doesn’t work as desired. Reasons to switch to second-line chemo include:
- Lack of response (the tumor failed to shrink).
- Progression (the cancer may have grown or spread further).
- Adverse side effects were too severe to continue.
The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.
Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:
- New or different chemotherapy drugs compared with prior lines.
- Surgery to debulk the tumor.
- Radiation for symptom control.
- Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
- Immunotherapy: agents that help the body’s immune system fight cancer cells.
- Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.
The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.
It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.
Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
Interventions to Consider Earlier
In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:
- Molecular testing.
- Palliation.
- Clinical trials.
- Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.
I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.
Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:
- Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
- Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
- Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.
Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.
Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.
Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.
Specific situations where discussing palliative care might be appropriate are:
- Soon after a cancer diagnosis.
- If the patient experiences significant side effects from cancer treatment.
- When considering different treatment options, palliative care can complement those treatments.
- In advanced stages of cancer, to focus on comfort and quality of life.
Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.
In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.
Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.
These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.
Read more about these leading innovations:
SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment
Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working
PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment
Using Live Cells from Patients to Find the Right Cancer Drug
Other innovative therapies under investigation could even be agnostic to cancer type:
Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?
High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells
All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions
Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.
Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.
I’m speaking in generalities, understanding that each cancer and each patient is unique.
Chemotherapy
Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.
Careful, compassionate communication between patient and physician is key. Goals and expectations must be clearly understood.
Organized chemotherapeutic efforts are further categorized as first line, second line, and third line.
First-line treatment. The initial round of recommended chemotherapy for a specific cancer. It is typically considered the most effective treatment for that type and stage of cancer on the basis of current research and clinical trials.
Second-line treatment. This is the treatment used if the first-line chemotherapy doesn’t work as desired. Reasons to switch to second-line chemo include:
- Lack of response (the tumor failed to shrink).
- Progression (the cancer may have grown or spread further).
- Adverse side effects were too severe to continue.
The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.
Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:
- New or different chemotherapy drugs compared with prior lines.
- Surgery to debulk the tumor.
- Radiation for symptom control.
- Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
- Immunotherapy: agents that help the body’s immune system fight cancer cells.
- Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.
The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.
It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.
Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
Interventions to Consider Earlier
In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:
- Molecular testing.
- Palliation.
- Clinical trials.
- Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.
I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.
Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:
- Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
- Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
- Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.
Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.
Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.
Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.
Specific situations where discussing palliative care might be appropriate are:
- Soon after a cancer diagnosis.
- If the patient experiences significant side effects from cancer treatment.
- When considering different treatment options, palliative care can complement those treatments.
- In advanced stages of cancer, to focus on comfort and quality of life.
Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.
In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.
Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.
These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.
Read more about these leading innovations:
SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment
Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working
PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment
Using Live Cells from Patients to Find the Right Cancer Drug
Other innovative therapies under investigation could even be agnostic to cancer type:
Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?
High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells
All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions
Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.
Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.