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Many Patients With Cancer Visit EDs Before Diagnosis
Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.
Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.
“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”
The findings were published online on November 4 in CMAJ).
Neurologic Cancers Prominent
In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.
Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.
Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.
Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).
The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.
“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.
The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.
The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
‘Unpacking the Data’
The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.
“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.
“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”
All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.
“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.
This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.
Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.
“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”
The findings were published online on November 4 in CMAJ).
Neurologic Cancers Prominent
In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.
Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.
Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.
Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).
The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.
“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.
The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.
The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
‘Unpacking the Data’
The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.
“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.
“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”
All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.
“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.
This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.
Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.
“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”
The findings were published online on November 4 in CMAJ).
Neurologic Cancers Prominent
In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.
Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.
Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.
Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).
The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.
“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.
The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.
The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
‘Unpacking the Data’
The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.
“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.
“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”
All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.
“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.
This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM CMAJ
Plasma Omega-6 and Omega-3 Fatty Acids Inversely Associated With Cancer
TOPLINE:
Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.
METHODOLOGY:
- Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
- They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
- Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
- Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
- The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.
TAKEAWAY:
- Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
- Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
- Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
- A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.
IN PRACTICE:
“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.
SOURCE:
The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.
LIMITATIONS:
The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants.
DISCLOSURES:
This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.
METHODOLOGY:
- Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
- They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
- Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
- Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
- The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.
TAKEAWAY:
- Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
- Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
- Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
- A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.
IN PRACTICE:
“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.
SOURCE:
The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.
LIMITATIONS:
The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants.
DISCLOSURES:
This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.
METHODOLOGY:
- Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
- They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
- Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
- Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
- The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.
TAKEAWAY:
- Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
- Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
- Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
- A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.
IN PRACTICE:
“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.
SOURCE:
The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.
LIMITATIONS:
The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants.
DISCLOSURES:
This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Climate Change Linked to Lung Cancer in Never-Smokers
The incidence of lung cancer in never-smokers (LCINS) is increasing, and experts think climate change may be driving the uptick.
LCINS differs histologically and epidemiologically from smoking-related cancers, occurring almost always as adenocarcinomas and mostly affecting women and individuals of Asian ancestry, according to a study published in Nature Reviews Clinical Oncology in January 2024. Cases of LCINS are estimated to be the fifth most common cause of cancer-related deaths worldwide.
These potential culprits are varied and sometimes interrelated — and they underscore the need for continued emphasis on environmental hazards, the panelists agreed.
Focusing on climate change — and taking action at the individual level — is a good place to start, said Leticia M. Nogueira, PhD, scientific director of health services research in the Surveillance and Health Equity Science Department of the American Cancer Society.
Long-Term Exposure to Wildfires Linked to Increased Cancer Risk
Climate change is associated with climate-driven disasters such as more intense hurricanes and more frequent wildfires that can expose populations to environmental carcinogens, Nogueira explained.
Such weather events disrupt the care of patients with cancer and lead to poorer outcomes, according to her own research. They also contribute to the rising incidence of LCINS, she said.
In a population-based study published in The Lancet Planetary Health, long-term exposure to wildfires was associated with an increased risk for lung cancer and brain tumors. Individuals exposed to a wildfire within 50 km of their residential locations in the prior decade has a 4.9% relatively higher incidence of lung cancer and a 10% relatively higher incidence of brain tumors.
“These findings are relevant on a global scale given the anticipated effects of climate change on wildfire frequency and severity,” the authors concluded, noting the study limitations and the need for further research.
How Clinicians Can Help
Nogueira urged attendees to take action to help improve healthcare outcomes.
“Let’s not forget that the healthcare system is one of the most emission-intensive industries in the world. Emissions from the US healthcare system exceed emission from the entire UK, and we can be doing much better.
“There is something for each one of us here today to do: We can champion environmentally responsible efforts at our institutions, we can engage with disaster preparedness and response ... and we can document ongoing suffering to increase awareness and incentivize action,” she said.
In a commentary published in CA: A Cancer Journal for Clinicians, Nogueira and her colleagues further addressed the links between climate change and cancer and listed various sources of greenhouse gas emissions and proposed interventions, including those associated with the healthcare industry.
“If you look at this list and say ‘No way — there is no chance my institution will do any of that,’ let me ask you something: Are you allowed to smoke on campus? How do you think that happened? How do you think that started?” she said, invoking Archimedes’ famous quote, “Give me a lever long enough, and I shall move the world.”
“You most certainly have the power to make a difference,” Nogueira said. “So recognize where your points of influence are – move your lever, move the world.”
A version of this article appeared on Medscape.com.
The incidence of lung cancer in never-smokers (LCINS) is increasing, and experts think climate change may be driving the uptick.
LCINS differs histologically and epidemiologically from smoking-related cancers, occurring almost always as adenocarcinomas and mostly affecting women and individuals of Asian ancestry, according to a study published in Nature Reviews Clinical Oncology in January 2024. Cases of LCINS are estimated to be the fifth most common cause of cancer-related deaths worldwide.
These potential culprits are varied and sometimes interrelated — and they underscore the need for continued emphasis on environmental hazards, the panelists agreed.
Focusing on climate change — and taking action at the individual level — is a good place to start, said Leticia M. Nogueira, PhD, scientific director of health services research in the Surveillance and Health Equity Science Department of the American Cancer Society.
Long-Term Exposure to Wildfires Linked to Increased Cancer Risk
Climate change is associated with climate-driven disasters such as more intense hurricanes and more frequent wildfires that can expose populations to environmental carcinogens, Nogueira explained.
Such weather events disrupt the care of patients with cancer and lead to poorer outcomes, according to her own research. They also contribute to the rising incidence of LCINS, she said.
In a population-based study published in The Lancet Planetary Health, long-term exposure to wildfires was associated with an increased risk for lung cancer and brain tumors. Individuals exposed to a wildfire within 50 km of their residential locations in the prior decade has a 4.9% relatively higher incidence of lung cancer and a 10% relatively higher incidence of brain tumors.
“These findings are relevant on a global scale given the anticipated effects of climate change on wildfire frequency and severity,” the authors concluded, noting the study limitations and the need for further research.
How Clinicians Can Help
Nogueira urged attendees to take action to help improve healthcare outcomes.
“Let’s not forget that the healthcare system is one of the most emission-intensive industries in the world. Emissions from the US healthcare system exceed emission from the entire UK, and we can be doing much better.
“There is something for each one of us here today to do: We can champion environmentally responsible efforts at our institutions, we can engage with disaster preparedness and response ... and we can document ongoing suffering to increase awareness and incentivize action,” she said.
In a commentary published in CA: A Cancer Journal for Clinicians, Nogueira and her colleagues further addressed the links between climate change and cancer and listed various sources of greenhouse gas emissions and proposed interventions, including those associated with the healthcare industry.
“If you look at this list and say ‘No way — there is no chance my institution will do any of that,’ let me ask you something: Are you allowed to smoke on campus? How do you think that happened? How do you think that started?” she said, invoking Archimedes’ famous quote, “Give me a lever long enough, and I shall move the world.”
“You most certainly have the power to make a difference,” Nogueira said. “So recognize where your points of influence are – move your lever, move the world.”
A version of this article appeared on Medscape.com.
The incidence of lung cancer in never-smokers (LCINS) is increasing, and experts think climate change may be driving the uptick.
LCINS differs histologically and epidemiologically from smoking-related cancers, occurring almost always as adenocarcinomas and mostly affecting women and individuals of Asian ancestry, according to a study published in Nature Reviews Clinical Oncology in January 2024. Cases of LCINS are estimated to be the fifth most common cause of cancer-related deaths worldwide.
These potential culprits are varied and sometimes interrelated — and they underscore the need for continued emphasis on environmental hazards, the panelists agreed.
Focusing on climate change — and taking action at the individual level — is a good place to start, said Leticia M. Nogueira, PhD, scientific director of health services research in the Surveillance and Health Equity Science Department of the American Cancer Society.
Long-Term Exposure to Wildfires Linked to Increased Cancer Risk
Climate change is associated with climate-driven disasters such as more intense hurricanes and more frequent wildfires that can expose populations to environmental carcinogens, Nogueira explained.
Such weather events disrupt the care of patients with cancer and lead to poorer outcomes, according to her own research. They also contribute to the rising incidence of LCINS, she said.
In a population-based study published in The Lancet Planetary Health, long-term exposure to wildfires was associated with an increased risk for lung cancer and brain tumors. Individuals exposed to a wildfire within 50 km of their residential locations in the prior decade has a 4.9% relatively higher incidence of lung cancer and a 10% relatively higher incidence of brain tumors.
“These findings are relevant on a global scale given the anticipated effects of climate change on wildfire frequency and severity,” the authors concluded, noting the study limitations and the need for further research.
How Clinicians Can Help
Nogueira urged attendees to take action to help improve healthcare outcomes.
“Let’s not forget that the healthcare system is one of the most emission-intensive industries in the world. Emissions from the US healthcare system exceed emission from the entire UK, and we can be doing much better.
“There is something for each one of us here today to do: We can champion environmentally responsible efforts at our institutions, we can engage with disaster preparedness and response ... and we can document ongoing suffering to increase awareness and incentivize action,” she said.
In a commentary published in CA: A Cancer Journal for Clinicians, Nogueira and her colleagues further addressed the links between climate change and cancer and listed various sources of greenhouse gas emissions and proposed interventions, including those associated with the healthcare industry.
“If you look at this list and say ‘No way — there is no chance my institution will do any of that,’ let me ask you something: Are you allowed to smoke on campus? How do you think that happened? How do you think that started?” she said, invoking Archimedes’ famous quote, “Give me a lever long enough, and I shall move the world.”
“You most certainly have the power to make a difference,” Nogueira said. “So recognize where your points of influence are – move your lever, move the world.”
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.
Should First-Line Dual Checkpoint Blockade Be Used for NSCLC With Specific Mutations?
according to the authors of a new paper.
These findings, drawn from a post hoc analysis of phase 3 data, are backed up by cell line and mouse data revealing clear mechanisms of efficacy, making the collective evidence compelling enough to reshape clinical practice, reported lead author Ferdinandos Skoulidis, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston.
“Although STK11 and KEAP1 mutations are associated with limited benefit from PD-1 or PD-L1 [PD-(L)1] inhibition, the association between these mutations and benefit from combinations of PD-(L)1 inhibitors with chemotherapy is not yet as well established,” the investigators wrote in Nature.
Skoulidis and colleagues conducted the subgroup analysis of POSEIDON trial data and characterized underlying biologic mechanisms using mouse models to address this knowledge gap.
What Were the Original Findings of POSEIDON?
The POSEIDON trial involved 1013 patients with metastatic NSCLC. Treatment arms included standard chemotherapy alone, chemotherapy plus programmed death ligand 1 (PD-L1) inhibitor durvalumab, and chemotherapy plus durvalumab and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor tremelimumab.
Adding durvalumab to chemotherapy significantly improved median progression-free survival (PFS) but not median overall survival (OS), while dual checkpoint blockade boosted both PFS and OS.
These findings provided support for the dual approach in the first-line setting, but not preferentially so. Experts called for more long-term data, questioned the survival benefit in terms of the increased toxicity, and noted the lack of biomarkers for patient selection.
What Did Post Hoc Analysis Highlight About POSEIDON?
The present analysis aimed to validate two actionable biomarkers.
“We and others have previously observed that alterations in STK11 and KEAP1 can promote an immunosuppressive tumor microenvironment and together might be responsible for half or more of the primary resistance to PD-(L)1 inhibition among patients with nsNSCLC when given as monotherapy,” Skoulidis and colleagues wrote.
From the original 1013 patients, 612 had non-squamous NSCLC and were evaluable for mutations. Among them, 87 had STK11 mutations and 37 had KEAP1 mutations.
As anticipated, patients in the STK11/KEAP1 subgroup saw little to no benefit from adding durvalumab to chemotherapy, but adding tremelimumab on top yielded notable improvement.
This was first observed in the objective response rate, which was 42.9% with dual checkpoint blockade plus chemotherapy vs 30.2% with single checkpoint blockade plus chemotherapy and 28% for chemotherapy alone. Durations of response improved in kind.
Survival outcomes also trended toward improvement in the dual checkpoint arm, which had a median OS of 15.8 months vs 7.3 months for durvalumab plus chemotherapy (hazard ratio [HR], 0.64; 95% CI, 0.40-1.04) and 10.5 months for chemotherapy alone (HR, 0.50; 95% CI, 0.29-0.87). PFS showed similar trends.
How Do Findings Relate to Previous NSCLC Subgroup Research?
Skoulidis and colleagues noted that their findings align with those of the CheckMate 9LA trial, which showed that patients with STK11 and/or KEAP1 mutations had better outcomes with dual checkpoint blockade plus chemotherapy than with chemotherapy alone.
“These data support the hypothesis that CTLA-4 inhibition can mitigate the resistance to chemotherapy plus PD-(L)1 inhibition observed in patients who have STK11 and/or KEAP1 mutations and suggest that this group of patients derives greater benefit from CTLA-4 inhibition than do patients who lack either alteration,” Skoulidis and colleagues wrote.
Grace Dy, MD, professor of oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center, Buffalo, New York, noted that in the present analysis, PD-L1 expression status did not predict outcomes; however, patients with STK11 and/or KEAP1 mutations typically have low or negative PD-L1 expression, which has been linked with better responses to CTLA-4 inhibition in multiple trials.
“In the CheckMate 227 and CheckMate 9LA studies, we have seen that patients with PD-L1–negative tumors appear to derive greater and more durable long-term overall survival benefit from dual immune checkpoint blockade compared to patients receiving anti-PD1-based therapy alone,” Dy said in a written comment. “While we take the necessary caveats on cross-trial comparisons, the same survival trend favoring CTLA-4-based immune checkpoint blockade is seen compared to the tail of the survival curves observed in PD-L1–negative patients enrolled in the KEYNOTE studies (KEYNOTE-189, KEYNOTE-407).”
Detecting improvements in survival within PD-L1 patients “may not be readily apparent until later when looking at the tail of the survival curves,” she added.
What Mechanisms of Action Explain Relative Benefits of Dual Checkpoint Blockade?
To elucidate underlying mechanisms of action, Skoulidis and colleagues conducted a series of experiments involving cell lines and mouse models of Stk11- and Keap1-deficient NSCLC.
“For us, it was critical to provide mechanistic support for the observed clinical benefit in POSEIDON, especially since this is based on a retrospective subgroup analysis,” Skoulidis said in an interview.
Their efforts revealed a strong link between the mutations and resistance to PD-(L)1 inhibition.
Inactivation of Stk11 and Keap1 promoted an immunosuppressive tumor microenvironment, marked by increased infiltration of suppressive myeloid cells and a reduction in CD8+ effector T cells. This immune imbalance contributed to evasion of immune destruction and limited the efficacy of programmed cell death protein 1 (PD-1) blockade.
Dual checkpoint blockade reprogrammed the immune microenvironment, leading to increased activation of CD4+ T helper (Th) cells, specifically the Th1 subtype, while inducing tumoricidal changes in myeloid cells. Consequently, antitumor responses improved, resulting in tumor regression and prolonged survival, compared with PD-1 monotherapy.
“Addition of CTLA-4 [inhibition] turns the two cardinal components of the suppressive microenvironment of these tumors on its head, and that’s why we believe we are observing this clinical benefit,” Skoulidis said. “This is not a mere association…but also based on very solid mechanistic data across a multitude of different models.”
Are Data Sufficient to Shift to First-Line Dual Checkpoint Blockade?
“Our work strengthens the available evidence that this regimen — and chemoimmunotherapy more broadly, with dual immune checkpoint blockade — constitutes a preferred approach for these patients,” Skoulidis said. “I personally, and I think physicians within MD Anderson, as well as a lot of physicians that I talk to, are already using — based on these data — the POSEIDON regimen, as well as, more broadly, chemoimmunotherapy with dual immune checkpoint for patients with these alterations.”
This view, however, remains contested by some oncologists.
Lei Deng, MD, assistant professor in the Division of Hematology and Oncology at the University of Washington, Fred Hutchinson Cancer Center, Seattle, called the new data “intriguing” and “hypothesis-generating,” but stopped short of supporting preferential first-line use.
“This study is a post hoc analysis, so you don’t have a lot of patients,” Deng said. “It is still not strong enough or definitive enough to make it standard of care to use dual checkpoint blockade for [patients with STK11 and/or KEAP1 mutations].”
The cell line and mouse data help explain biologic mechanisms of efficacy, he said, but these findings do not obviate toxicity concerns.
“You are adding one more agent, and this agent is more toxic than single checkpoint blockade,” Deng said. “So, if you weigh the risk, it is known, [but] the benefit is suggestive. I am not sure if the risk-benefit ratio would argue for routine implementation of this regimen yet.”
On the other hand, he noted, the combination is the US Food and Drug Administration–approved in this setting, so “it is not wrong to use it.”
Jyoti Malhotra, MD, director of thoracic medical oncology at City of Hope Orange County in Irvine, California, had a similar take.
“The clinical data presented so far is exploratory and limited by the small sample size,” Malhotra said in a written comment. “Data from an ongoing phase 3 trial (TRITON) is awaited before dual checkpoint blockade becomes the standard of care in this setting.”
Hossein Borghaei, DO, chief of the Division of Thoracic Medical Oncology at Fox Chase Cancer Center, Philadelphia, was also unequivocal when asked if dual checkpoint blockade with chemotherapy should be considered the preferred first-line treatment option in patients with STK11 and/or KEAP1 mutations.
“No,” he said in a written comment. “The data and the hypothesis are very strong, but it is all based on retrospective clinical data, cell line data, and mouse models. We need a randomized study to test the hypothesis.”
Incidentally, Borghaei is on the steering committee for the TRITON trial. He shared this potential conflict of interest before praising Skoulidis and colleagues for their efforts, noting that the present findings underscore the broader importance of widespread tumor profiling and access to resultant data.
“This is a beautiful story that has developed over the last few years based on the research by the group from MD Anderson who has reported the current Nature article,” he said. “This highlights the possible utility of collecting sequencing data on [all] patients’ tumors. These sorts of understandings and new ideas could arise only if there is access to this information.”
The study was supported by AstraZeneca, the National Cancer Institute, the Gunnigar Fund, and others. The investigators disclosed additional relationships with Novartis, Merck, Amgen, and others. Deng disclosed relationships with Merck, BridgeBio, MJH Life Sciences, and others. Dy disclosed relationships with Eli Lilly and Company, Janssen Pharmaceuticals, Meru, and others. Malhotra has previously served as a consultant for AstraZeneca. Borghaei has served as a consultant for AstraZeneca and is on the steering committee for the TRITON trial.
A version of this article appeared on Medscape.com.
according to the authors of a new paper.
These findings, drawn from a post hoc analysis of phase 3 data, are backed up by cell line and mouse data revealing clear mechanisms of efficacy, making the collective evidence compelling enough to reshape clinical practice, reported lead author Ferdinandos Skoulidis, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston.
“Although STK11 and KEAP1 mutations are associated with limited benefit from PD-1 or PD-L1 [PD-(L)1] inhibition, the association between these mutations and benefit from combinations of PD-(L)1 inhibitors with chemotherapy is not yet as well established,” the investigators wrote in Nature.
Skoulidis and colleagues conducted the subgroup analysis of POSEIDON trial data and characterized underlying biologic mechanisms using mouse models to address this knowledge gap.
What Were the Original Findings of POSEIDON?
The POSEIDON trial involved 1013 patients with metastatic NSCLC. Treatment arms included standard chemotherapy alone, chemotherapy plus programmed death ligand 1 (PD-L1) inhibitor durvalumab, and chemotherapy plus durvalumab and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor tremelimumab.
Adding durvalumab to chemotherapy significantly improved median progression-free survival (PFS) but not median overall survival (OS), while dual checkpoint blockade boosted both PFS and OS.
These findings provided support for the dual approach in the first-line setting, but not preferentially so. Experts called for more long-term data, questioned the survival benefit in terms of the increased toxicity, and noted the lack of biomarkers for patient selection.
What Did Post Hoc Analysis Highlight About POSEIDON?
The present analysis aimed to validate two actionable biomarkers.
“We and others have previously observed that alterations in STK11 and KEAP1 can promote an immunosuppressive tumor microenvironment and together might be responsible for half or more of the primary resistance to PD-(L)1 inhibition among patients with nsNSCLC when given as monotherapy,” Skoulidis and colleagues wrote.
From the original 1013 patients, 612 had non-squamous NSCLC and were evaluable for mutations. Among them, 87 had STK11 mutations and 37 had KEAP1 mutations.
As anticipated, patients in the STK11/KEAP1 subgroup saw little to no benefit from adding durvalumab to chemotherapy, but adding tremelimumab on top yielded notable improvement.
This was first observed in the objective response rate, which was 42.9% with dual checkpoint blockade plus chemotherapy vs 30.2% with single checkpoint blockade plus chemotherapy and 28% for chemotherapy alone. Durations of response improved in kind.
Survival outcomes also trended toward improvement in the dual checkpoint arm, which had a median OS of 15.8 months vs 7.3 months for durvalumab plus chemotherapy (hazard ratio [HR], 0.64; 95% CI, 0.40-1.04) and 10.5 months for chemotherapy alone (HR, 0.50; 95% CI, 0.29-0.87). PFS showed similar trends.
How Do Findings Relate to Previous NSCLC Subgroup Research?
Skoulidis and colleagues noted that their findings align with those of the CheckMate 9LA trial, which showed that patients with STK11 and/or KEAP1 mutations had better outcomes with dual checkpoint blockade plus chemotherapy than with chemotherapy alone.
“These data support the hypothesis that CTLA-4 inhibition can mitigate the resistance to chemotherapy plus PD-(L)1 inhibition observed in patients who have STK11 and/or KEAP1 mutations and suggest that this group of patients derives greater benefit from CTLA-4 inhibition than do patients who lack either alteration,” Skoulidis and colleagues wrote.
Grace Dy, MD, professor of oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center, Buffalo, New York, noted that in the present analysis, PD-L1 expression status did not predict outcomes; however, patients with STK11 and/or KEAP1 mutations typically have low or negative PD-L1 expression, which has been linked with better responses to CTLA-4 inhibition in multiple trials.
“In the CheckMate 227 and CheckMate 9LA studies, we have seen that patients with PD-L1–negative tumors appear to derive greater and more durable long-term overall survival benefit from dual immune checkpoint blockade compared to patients receiving anti-PD1-based therapy alone,” Dy said in a written comment. “While we take the necessary caveats on cross-trial comparisons, the same survival trend favoring CTLA-4-based immune checkpoint blockade is seen compared to the tail of the survival curves observed in PD-L1–negative patients enrolled in the KEYNOTE studies (KEYNOTE-189, KEYNOTE-407).”
Detecting improvements in survival within PD-L1 patients “may not be readily apparent until later when looking at the tail of the survival curves,” she added.
What Mechanisms of Action Explain Relative Benefits of Dual Checkpoint Blockade?
To elucidate underlying mechanisms of action, Skoulidis and colleagues conducted a series of experiments involving cell lines and mouse models of Stk11- and Keap1-deficient NSCLC.
“For us, it was critical to provide mechanistic support for the observed clinical benefit in POSEIDON, especially since this is based on a retrospective subgroup analysis,” Skoulidis said in an interview.
Their efforts revealed a strong link between the mutations and resistance to PD-(L)1 inhibition.
Inactivation of Stk11 and Keap1 promoted an immunosuppressive tumor microenvironment, marked by increased infiltration of suppressive myeloid cells and a reduction in CD8+ effector T cells. This immune imbalance contributed to evasion of immune destruction and limited the efficacy of programmed cell death protein 1 (PD-1) blockade.
Dual checkpoint blockade reprogrammed the immune microenvironment, leading to increased activation of CD4+ T helper (Th) cells, specifically the Th1 subtype, while inducing tumoricidal changes in myeloid cells. Consequently, antitumor responses improved, resulting in tumor regression and prolonged survival, compared with PD-1 monotherapy.
“Addition of CTLA-4 [inhibition] turns the two cardinal components of the suppressive microenvironment of these tumors on its head, and that’s why we believe we are observing this clinical benefit,” Skoulidis said. “This is not a mere association…but also based on very solid mechanistic data across a multitude of different models.”
Are Data Sufficient to Shift to First-Line Dual Checkpoint Blockade?
“Our work strengthens the available evidence that this regimen — and chemoimmunotherapy more broadly, with dual immune checkpoint blockade — constitutes a preferred approach for these patients,” Skoulidis said. “I personally, and I think physicians within MD Anderson, as well as a lot of physicians that I talk to, are already using — based on these data — the POSEIDON regimen, as well as, more broadly, chemoimmunotherapy with dual immune checkpoint for patients with these alterations.”
This view, however, remains contested by some oncologists.
Lei Deng, MD, assistant professor in the Division of Hematology and Oncology at the University of Washington, Fred Hutchinson Cancer Center, Seattle, called the new data “intriguing” and “hypothesis-generating,” but stopped short of supporting preferential first-line use.
“This study is a post hoc analysis, so you don’t have a lot of patients,” Deng said. “It is still not strong enough or definitive enough to make it standard of care to use dual checkpoint blockade for [patients with STK11 and/or KEAP1 mutations].”
The cell line and mouse data help explain biologic mechanisms of efficacy, he said, but these findings do not obviate toxicity concerns.
“You are adding one more agent, and this agent is more toxic than single checkpoint blockade,” Deng said. “So, if you weigh the risk, it is known, [but] the benefit is suggestive. I am not sure if the risk-benefit ratio would argue for routine implementation of this regimen yet.”
On the other hand, he noted, the combination is the US Food and Drug Administration–approved in this setting, so “it is not wrong to use it.”
Jyoti Malhotra, MD, director of thoracic medical oncology at City of Hope Orange County in Irvine, California, had a similar take.
“The clinical data presented so far is exploratory and limited by the small sample size,” Malhotra said in a written comment. “Data from an ongoing phase 3 trial (TRITON) is awaited before dual checkpoint blockade becomes the standard of care in this setting.”
Hossein Borghaei, DO, chief of the Division of Thoracic Medical Oncology at Fox Chase Cancer Center, Philadelphia, was also unequivocal when asked if dual checkpoint blockade with chemotherapy should be considered the preferred first-line treatment option in patients with STK11 and/or KEAP1 mutations.
“No,” he said in a written comment. “The data and the hypothesis are very strong, but it is all based on retrospective clinical data, cell line data, and mouse models. We need a randomized study to test the hypothesis.”
Incidentally, Borghaei is on the steering committee for the TRITON trial. He shared this potential conflict of interest before praising Skoulidis and colleagues for their efforts, noting that the present findings underscore the broader importance of widespread tumor profiling and access to resultant data.
“This is a beautiful story that has developed over the last few years based on the research by the group from MD Anderson who has reported the current Nature article,” he said. “This highlights the possible utility of collecting sequencing data on [all] patients’ tumors. These sorts of understandings and new ideas could arise only if there is access to this information.”
The study was supported by AstraZeneca, the National Cancer Institute, the Gunnigar Fund, and others. The investigators disclosed additional relationships with Novartis, Merck, Amgen, and others. Deng disclosed relationships with Merck, BridgeBio, MJH Life Sciences, and others. Dy disclosed relationships with Eli Lilly and Company, Janssen Pharmaceuticals, Meru, and others. Malhotra has previously served as a consultant for AstraZeneca. Borghaei has served as a consultant for AstraZeneca and is on the steering committee for the TRITON trial.
A version of this article appeared on Medscape.com.
according to the authors of a new paper.
These findings, drawn from a post hoc analysis of phase 3 data, are backed up by cell line and mouse data revealing clear mechanisms of efficacy, making the collective evidence compelling enough to reshape clinical practice, reported lead author Ferdinandos Skoulidis, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston.
“Although STK11 and KEAP1 mutations are associated with limited benefit from PD-1 or PD-L1 [PD-(L)1] inhibition, the association between these mutations and benefit from combinations of PD-(L)1 inhibitors with chemotherapy is not yet as well established,” the investigators wrote in Nature.
Skoulidis and colleagues conducted the subgroup analysis of POSEIDON trial data and characterized underlying biologic mechanisms using mouse models to address this knowledge gap.
What Were the Original Findings of POSEIDON?
The POSEIDON trial involved 1013 patients with metastatic NSCLC. Treatment arms included standard chemotherapy alone, chemotherapy plus programmed death ligand 1 (PD-L1) inhibitor durvalumab, and chemotherapy plus durvalumab and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor tremelimumab.
Adding durvalumab to chemotherapy significantly improved median progression-free survival (PFS) but not median overall survival (OS), while dual checkpoint blockade boosted both PFS and OS.
These findings provided support for the dual approach in the first-line setting, but not preferentially so. Experts called for more long-term data, questioned the survival benefit in terms of the increased toxicity, and noted the lack of biomarkers for patient selection.
What Did Post Hoc Analysis Highlight About POSEIDON?
The present analysis aimed to validate two actionable biomarkers.
“We and others have previously observed that alterations in STK11 and KEAP1 can promote an immunosuppressive tumor microenvironment and together might be responsible for half or more of the primary resistance to PD-(L)1 inhibition among patients with nsNSCLC when given as monotherapy,” Skoulidis and colleagues wrote.
From the original 1013 patients, 612 had non-squamous NSCLC and were evaluable for mutations. Among them, 87 had STK11 mutations and 37 had KEAP1 mutations.
As anticipated, patients in the STK11/KEAP1 subgroup saw little to no benefit from adding durvalumab to chemotherapy, but adding tremelimumab on top yielded notable improvement.
This was first observed in the objective response rate, which was 42.9% with dual checkpoint blockade plus chemotherapy vs 30.2% with single checkpoint blockade plus chemotherapy and 28% for chemotherapy alone. Durations of response improved in kind.
Survival outcomes also trended toward improvement in the dual checkpoint arm, which had a median OS of 15.8 months vs 7.3 months for durvalumab plus chemotherapy (hazard ratio [HR], 0.64; 95% CI, 0.40-1.04) and 10.5 months for chemotherapy alone (HR, 0.50; 95% CI, 0.29-0.87). PFS showed similar trends.
How Do Findings Relate to Previous NSCLC Subgroup Research?
Skoulidis and colleagues noted that their findings align with those of the CheckMate 9LA trial, which showed that patients with STK11 and/or KEAP1 mutations had better outcomes with dual checkpoint blockade plus chemotherapy than with chemotherapy alone.
“These data support the hypothesis that CTLA-4 inhibition can mitigate the resistance to chemotherapy plus PD-(L)1 inhibition observed in patients who have STK11 and/or KEAP1 mutations and suggest that this group of patients derives greater benefit from CTLA-4 inhibition than do patients who lack either alteration,” Skoulidis and colleagues wrote.
Grace Dy, MD, professor of oncology in the Department of Medicine at Roswell Park Comprehensive Cancer Center, Buffalo, New York, noted that in the present analysis, PD-L1 expression status did not predict outcomes; however, patients with STK11 and/or KEAP1 mutations typically have low or negative PD-L1 expression, which has been linked with better responses to CTLA-4 inhibition in multiple trials.
“In the CheckMate 227 and CheckMate 9LA studies, we have seen that patients with PD-L1–negative tumors appear to derive greater and more durable long-term overall survival benefit from dual immune checkpoint blockade compared to patients receiving anti-PD1-based therapy alone,” Dy said in a written comment. “While we take the necessary caveats on cross-trial comparisons, the same survival trend favoring CTLA-4-based immune checkpoint blockade is seen compared to the tail of the survival curves observed in PD-L1–negative patients enrolled in the KEYNOTE studies (KEYNOTE-189, KEYNOTE-407).”
Detecting improvements in survival within PD-L1 patients “may not be readily apparent until later when looking at the tail of the survival curves,” she added.
What Mechanisms of Action Explain Relative Benefits of Dual Checkpoint Blockade?
To elucidate underlying mechanisms of action, Skoulidis and colleagues conducted a series of experiments involving cell lines and mouse models of Stk11- and Keap1-deficient NSCLC.
“For us, it was critical to provide mechanistic support for the observed clinical benefit in POSEIDON, especially since this is based on a retrospective subgroup analysis,” Skoulidis said in an interview.
Their efforts revealed a strong link between the mutations and resistance to PD-(L)1 inhibition.
Inactivation of Stk11 and Keap1 promoted an immunosuppressive tumor microenvironment, marked by increased infiltration of suppressive myeloid cells and a reduction in CD8+ effector T cells. This immune imbalance contributed to evasion of immune destruction and limited the efficacy of programmed cell death protein 1 (PD-1) blockade.
Dual checkpoint blockade reprogrammed the immune microenvironment, leading to increased activation of CD4+ T helper (Th) cells, specifically the Th1 subtype, while inducing tumoricidal changes in myeloid cells. Consequently, antitumor responses improved, resulting in tumor regression and prolonged survival, compared with PD-1 monotherapy.
“Addition of CTLA-4 [inhibition] turns the two cardinal components of the suppressive microenvironment of these tumors on its head, and that’s why we believe we are observing this clinical benefit,” Skoulidis said. “This is not a mere association…but also based on very solid mechanistic data across a multitude of different models.”
Are Data Sufficient to Shift to First-Line Dual Checkpoint Blockade?
“Our work strengthens the available evidence that this regimen — and chemoimmunotherapy more broadly, with dual immune checkpoint blockade — constitutes a preferred approach for these patients,” Skoulidis said. “I personally, and I think physicians within MD Anderson, as well as a lot of physicians that I talk to, are already using — based on these data — the POSEIDON regimen, as well as, more broadly, chemoimmunotherapy with dual immune checkpoint for patients with these alterations.”
This view, however, remains contested by some oncologists.
Lei Deng, MD, assistant professor in the Division of Hematology and Oncology at the University of Washington, Fred Hutchinson Cancer Center, Seattle, called the new data “intriguing” and “hypothesis-generating,” but stopped short of supporting preferential first-line use.
“This study is a post hoc analysis, so you don’t have a lot of patients,” Deng said. “It is still not strong enough or definitive enough to make it standard of care to use dual checkpoint blockade for [patients with STK11 and/or KEAP1 mutations].”
The cell line and mouse data help explain biologic mechanisms of efficacy, he said, but these findings do not obviate toxicity concerns.
“You are adding one more agent, and this agent is more toxic than single checkpoint blockade,” Deng said. “So, if you weigh the risk, it is known, [but] the benefit is suggestive. I am not sure if the risk-benefit ratio would argue for routine implementation of this regimen yet.”
On the other hand, he noted, the combination is the US Food and Drug Administration–approved in this setting, so “it is not wrong to use it.”
Jyoti Malhotra, MD, director of thoracic medical oncology at City of Hope Orange County in Irvine, California, had a similar take.
“The clinical data presented so far is exploratory and limited by the small sample size,” Malhotra said in a written comment. “Data from an ongoing phase 3 trial (TRITON) is awaited before dual checkpoint blockade becomes the standard of care in this setting.”
Hossein Borghaei, DO, chief of the Division of Thoracic Medical Oncology at Fox Chase Cancer Center, Philadelphia, was also unequivocal when asked if dual checkpoint blockade with chemotherapy should be considered the preferred first-line treatment option in patients with STK11 and/or KEAP1 mutations.
“No,” he said in a written comment. “The data and the hypothesis are very strong, but it is all based on retrospective clinical data, cell line data, and mouse models. We need a randomized study to test the hypothesis.”
Incidentally, Borghaei is on the steering committee for the TRITON trial. He shared this potential conflict of interest before praising Skoulidis and colleagues for their efforts, noting that the present findings underscore the broader importance of widespread tumor profiling and access to resultant data.
“This is a beautiful story that has developed over the last few years based on the research by the group from MD Anderson who has reported the current Nature article,” he said. “This highlights the possible utility of collecting sequencing data on [all] patients’ tumors. These sorts of understandings and new ideas could arise only if there is access to this information.”
The study was supported by AstraZeneca, the National Cancer Institute, the Gunnigar Fund, and others. The investigators disclosed additional relationships with Novartis, Merck, Amgen, and others. Deng disclosed relationships with Merck, BridgeBio, MJH Life Sciences, and others. Dy disclosed relationships with Eli Lilly and Company, Janssen Pharmaceuticals, Meru, and others. Malhotra has previously served as a consultant for AstraZeneca. Borghaei has served as a consultant for AstraZeneca and is on the steering committee for the TRITON trial.
A version of this article appeared on Medscape.com.
Cannabis in Cancer: What Oncologists and Patients Should Know
first, and oncologists may be hesitant to broach the topic with their patients.
Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.
According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.
Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.
“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”
But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.
So, “let yourself off the hook,” Worster urged.
Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.
Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
Evidence on Cannabis During Cancer Care
A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.
In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.
Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.
The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.
The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.
The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.
Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.
There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.
The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
Talking to Patients About Cannabis
Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.
To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.
One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.
The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.
But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”
Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.
Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.
It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.
CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.
Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.
The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”
Worster disclosed that she is a medical consultant for EO Care.
A version of this article appeared on Medscape.com.
first, and oncologists may be hesitant to broach the topic with their patients.
Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.
According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.
Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.
“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”
But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.
So, “let yourself off the hook,” Worster urged.
Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.
Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
Evidence on Cannabis During Cancer Care
A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.
In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.
Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.
The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.
The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.
The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.
Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.
There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.
The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
Talking to Patients About Cannabis
Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.
To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.
One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.
The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.
But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”
Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.
Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.
It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.
CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.
Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.
The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”
Worster disclosed that she is a medical consultant for EO Care.
A version of this article appeared on Medscape.com.
first, and oncologists may be hesitant to broach the topic with their patients.
Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.
According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.
Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.
“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”
But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.
So, “let yourself off the hook,” Worster urged.
Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.
Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
Evidence on Cannabis During Cancer Care
A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.
In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.
Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.
The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.
The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.
The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.
Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.
There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.
The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
Talking to Patients About Cannabis
Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.
To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.
One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.
The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.
But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”
Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.
Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.
It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.
CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.
Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.
The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”
Worster disclosed that she is a medical consultant for EO Care.
A version of this article appeared on Medscape.com.
Gotistobart Trial for NSCLC on Partial Clinical Hold
Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.
“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”
Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
A version of this article appeared on Medscape.com.
Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.
“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”
Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
A version of this article appeared on Medscape.com.
Gotistobart is a next-generation anti-cytotoxic T-lymphocyte-associated protein 4 antibody candidate in late-stage clinical development for various cancer indications. PRESERVE-003 is an open-label randomized trial assessing the safety and efficacy of the agent vs docetaxel as monotherapy in patients with metastatic NSCLC that progressed despite prior treatment with a programmed cell death protein 1 or programmed death ligand 1 inhibitor.
“A recent assessment of the trial data by the independent data monitoring committee identified a possible variance in population results,” according to a regulatory document from the United States Securities and Exchange Commission relating to the clinical hold. “Consequently, OncoC4 and BioNTech decided to proactively pause enrollment of new patients and informed the FDA of the possible variance for further alignment.”
Patients already enrolled in the trial will continue to receive treatment. Ongoing trials of gotistobart for other indications are not affected by the hold, according to the notice.
A version of this article appeared on Medscape.com.
Risk Assessment Tool Can Help Predict Fractures in Cancer
TOPLINE:
METHODOLOGY:
- Cancer-specific guidelines recommend using FRAX to assess fracture risk, but its applicability in patients with cancer remains unclear.
- This retrospective cohort study included 9877 patients with cancer (mean age, 67.1 years) and 45,875 matched control individuals without cancer (mean age, 66.2 years). All participants had dual-energy x-ray absorptiometry (DXA) scans.
- Researchers collected data on bone mineral density and fractures. The 10-year probabilities of major osteoporotic fractures and hip fractures were calculated using FRAX, and the observed 10-year probabilities of these fractures were compared with FRAX-derived probabilities.
- Compared with individuals without cancer, patients with cancer had a shorter mean follow-up duration (8.5 vs 7.6 years), a slightly higher mean body mass index, and a higher percentage of parental hip fractures (7.0% vs 8.2%); additionally, patients with cancer were more likely to have secondary causes of osteoporosis (10% vs 38.4%) and less likely to receive osteoporosis medication (9.9% vs 4.2%).
TAKEAWAY:
- Compared with individuals without cancer, patients with cancer had a significantly higher incidence rate of major fractures (12.9 vs 14.5 per 1000 person-years) and hip fractures (3.5 vs 4.2 per 1000 person-years).
- FRAX with bone mineral density exhibited excellent calibration for predicting major osteoporotic fractures (slope, 1.03) and hip fractures (0.97) in patients with cancer, regardless of the site of cancer diagnosis. FRAX without bone mineral density, however, underestimated the risk for both major (0.87) and hip fractures (0.72).
- In patients with cancer, FRAX with bone mineral density findings were associated with incident major osteoporotic fractures (hazard ratio [HR] per SD, 1.84) and hip fractures (HR per SD, 3.61).
- When models were adjusted for FRAX with bone mineral density, patients with cancer had an increased risk for both major osteoporotic fractures (HR, 1.17) and hip fractures (HR, 1.30). No difference was found in the risk for fracture between patients with and individuals without cancer when the models were adjusted for FRAX without bone mineral density, even when considering osteoporosis medication use.
IN PRACTICE:
“This retrospective cohort study demonstrates that individuals with cancer are at higher risk of fracture than individuals without cancer and that FRAX, particularly with BMD [bone mineral density], may accurately predict fracture risk in this population. These results, along with the known mortality risk of osteoporotic fractures among cancer survivors, further emphasize the clinical importance of closing the current osteoporosis care gap among cancer survivors,” the authors wrote.
SOURCE:
This study, led by Carrie Ye, MD, MPH, University of Alberta, Edmonton, Alberta, Canada, was published online in JAMA Oncology.
LIMITATIONS:
This study cohort included a selected group of cancer survivors who were referred for DXA scans and may not represent the general cancer population. The cohort consisted predominantly of women, limiting the generalizability to men with cancer. Given the heterogeneity of the population, the findings may not be applicable to all cancer subgroups. Information on cancer stage or the presence of bone metastases at the time of fracture risk assessment was lacking, which could have affected the findings.
DISCLOSURES:
This study was funded by the CancerCare Manitoba Foundation. Three authors reported having ties with various sources, including two who received grants from various organizations.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Cancer-specific guidelines recommend using FRAX to assess fracture risk, but its applicability in patients with cancer remains unclear.
- This retrospective cohort study included 9877 patients with cancer (mean age, 67.1 years) and 45,875 matched control individuals without cancer (mean age, 66.2 years). All participants had dual-energy x-ray absorptiometry (DXA) scans.
- Researchers collected data on bone mineral density and fractures. The 10-year probabilities of major osteoporotic fractures and hip fractures were calculated using FRAX, and the observed 10-year probabilities of these fractures were compared with FRAX-derived probabilities.
- Compared with individuals without cancer, patients with cancer had a shorter mean follow-up duration (8.5 vs 7.6 years), a slightly higher mean body mass index, and a higher percentage of parental hip fractures (7.0% vs 8.2%); additionally, patients with cancer were more likely to have secondary causes of osteoporosis (10% vs 38.4%) and less likely to receive osteoporosis medication (9.9% vs 4.2%).
TAKEAWAY:
- Compared with individuals without cancer, patients with cancer had a significantly higher incidence rate of major fractures (12.9 vs 14.5 per 1000 person-years) and hip fractures (3.5 vs 4.2 per 1000 person-years).
- FRAX with bone mineral density exhibited excellent calibration for predicting major osteoporotic fractures (slope, 1.03) and hip fractures (0.97) in patients with cancer, regardless of the site of cancer diagnosis. FRAX without bone mineral density, however, underestimated the risk for both major (0.87) and hip fractures (0.72).
- In patients with cancer, FRAX with bone mineral density findings were associated with incident major osteoporotic fractures (hazard ratio [HR] per SD, 1.84) and hip fractures (HR per SD, 3.61).
- When models were adjusted for FRAX with bone mineral density, patients with cancer had an increased risk for both major osteoporotic fractures (HR, 1.17) and hip fractures (HR, 1.30). No difference was found in the risk for fracture between patients with and individuals without cancer when the models were adjusted for FRAX without bone mineral density, even when considering osteoporosis medication use.
IN PRACTICE:
“This retrospective cohort study demonstrates that individuals with cancer are at higher risk of fracture than individuals without cancer and that FRAX, particularly with BMD [bone mineral density], may accurately predict fracture risk in this population. These results, along with the known mortality risk of osteoporotic fractures among cancer survivors, further emphasize the clinical importance of closing the current osteoporosis care gap among cancer survivors,” the authors wrote.
SOURCE:
This study, led by Carrie Ye, MD, MPH, University of Alberta, Edmonton, Alberta, Canada, was published online in JAMA Oncology.
LIMITATIONS:
This study cohort included a selected group of cancer survivors who were referred for DXA scans and may not represent the general cancer population. The cohort consisted predominantly of women, limiting the generalizability to men with cancer. Given the heterogeneity of the population, the findings may not be applicable to all cancer subgroups. Information on cancer stage or the presence of bone metastases at the time of fracture risk assessment was lacking, which could have affected the findings.
DISCLOSURES:
This study was funded by the CancerCare Manitoba Foundation. Three authors reported having ties with various sources, including two who received grants from various organizations.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Cancer-specific guidelines recommend using FRAX to assess fracture risk, but its applicability in patients with cancer remains unclear.
- This retrospective cohort study included 9877 patients with cancer (mean age, 67.1 years) and 45,875 matched control individuals without cancer (mean age, 66.2 years). All participants had dual-energy x-ray absorptiometry (DXA) scans.
- Researchers collected data on bone mineral density and fractures. The 10-year probabilities of major osteoporotic fractures and hip fractures were calculated using FRAX, and the observed 10-year probabilities of these fractures were compared with FRAX-derived probabilities.
- Compared with individuals without cancer, patients with cancer had a shorter mean follow-up duration (8.5 vs 7.6 years), a slightly higher mean body mass index, and a higher percentage of parental hip fractures (7.0% vs 8.2%); additionally, patients with cancer were more likely to have secondary causes of osteoporosis (10% vs 38.4%) and less likely to receive osteoporosis medication (9.9% vs 4.2%).
TAKEAWAY:
- Compared with individuals without cancer, patients with cancer had a significantly higher incidence rate of major fractures (12.9 vs 14.5 per 1000 person-years) and hip fractures (3.5 vs 4.2 per 1000 person-years).
- FRAX with bone mineral density exhibited excellent calibration for predicting major osteoporotic fractures (slope, 1.03) and hip fractures (0.97) in patients with cancer, regardless of the site of cancer diagnosis. FRAX without bone mineral density, however, underestimated the risk for both major (0.87) and hip fractures (0.72).
- In patients with cancer, FRAX with bone mineral density findings were associated with incident major osteoporotic fractures (hazard ratio [HR] per SD, 1.84) and hip fractures (HR per SD, 3.61).
- When models were adjusted for FRAX with bone mineral density, patients with cancer had an increased risk for both major osteoporotic fractures (HR, 1.17) and hip fractures (HR, 1.30). No difference was found in the risk for fracture between patients with and individuals without cancer when the models were adjusted for FRAX without bone mineral density, even when considering osteoporosis medication use.
IN PRACTICE:
“This retrospective cohort study demonstrates that individuals with cancer are at higher risk of fracture than individuals without cancer and that FRAX, particularly with BMD [bone mineral density], may accurately predict fracture risk in this population. These results, along with the known mortality risk of osteoporotic fractures among cancer survivors, further emphasize the clinical importance of closing the current osteoporosis care gap among cancer survivors,” the authors wrote.
SOURCE:
This study, led by Carrie Ye, MD, MPH, University of Alberta, Edmonton, Alberta, Canada, was published online in JAMA Oncology.
LIMITATIONS:
This study cohort included a selected group of cancer survivors who were referred for DXA scans and may not represent the general cancer population. The cohort consisted predominantly of women, limiting the generalizability to men with cancer. Given the heterogeneity of the population, the findings may not be applicable to all cancer subgroups. Information on cancer stage or the presence of bone metastases at the time of fracture risk assessment was lacking, which could have affected the findings.
DISCLOSURES:
This study was funded by the CancerCare Manitoba Foundation. Three authors reported having ties with various sources, including two who received grants from various organizations.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
The New Cancer Stats Might Look Like a Death Sentence. They Aren’t.
Cancer is becoming more common in younger generations. Data show that people under 50 are experiencing higher rates of cancer than any generation before them. As a genetic counselor, I hoped these upward trends in early-onset malignancies would slow with a better understanding of risk factors and prevention strategies. Unfortunately, the opposite is happening. Recent findings from the American Cancer Society reveal that the incidence of at least 17 of 34 cancer types is rising among GenX and Millennials.
These statistics are alarming. I appreciate how easy it is for patients to get lost in the headlines about cancer, which may shape how they approach their healthcare. Each year, millions of Americans miss critical cancer screenings, with many citing fear of a positive test result as a leading reason. Others believe, despite the statistics, that cancer is not something they need to worry about until they are older. And then, of course, getting screened is not as easy as it should be.
In my work, I meet with people from both younger and older generations who have either faced cancer themselves or witnessed a loved one experience the disease. One of the most common sentiments I hear from these patients is the desire to catch cancer earlier. My answer is always this: The first and most important step everyone can take is understanding their risk.
For some, knowing they are at increased risk for cancer means starting screenings earlier — sometimes as early as age 25 — or getting screened with a more sensitive test.
This proactive approach is the right one. It also significantly reduces the burden of total and cancer-specific healthcare costs. While screening may carry some potential risks, clinicians can minimize these risks by adhering to evidence-based guidelines, such as those from the American Cancer Society, and ensuring there is appropriate discussion of treatment options when a diagnosis is made.
Normalizing Cancer Risk Assessment and Screening
A detailed cancer risk assessment and education about signs and symptoms should be part of every preventive care visit, regardless of someone’s age. Further, that cancer risk assessment should lead to clear recommendations and support for taking the next steps.
This is where care advocacy and patient navigation come in. Care advocacy can improve outcomes at every stage of the cancer journey, from increasing screening rates to improving quality of life for survivors. I’ve seen first-hand how care advocates help patients overcome hurdles like long wait times for appointments they need, making both screening and diagnostic care easier to access.
Now, with the finalization of a new rule from the Centers for Medicare & Medicaid Services, providers can bill for oncology navigation services that occur under their supervision. This formal recognition of care navigation affirms the value of these services not just clinically but financially as well. It will be through methods like care navigation, targeted outreach, and engaging educational resources — built into and covered by health plans — that patients will feel more in control over their health and have tools to help minimize the effects of cancer on the rest of their lives.
These services benefit healthcare providers as well. Care navigation supports clinical care teams, from primary care providers to oncologists, by ensuring patients are seen before their cancer progresses to a more advanced stage. And even if patients follow screening recommendations for the rest of their lives and never get a positive result, they’ve still gained something invaluable: peace of mind, knowing they’ve taken an active role in their health.
Fighting Fear With Routine
Treating cancer as a normal part of young people’s healthcare means helping them envision the disease as a condition that can be treated, much like a diagnosis of diabetes or high cholesterol. This mindset shift means quickly following up on a concerning symptom or screening result and reducing the time to start treatment if needed. And with treatment options and success rates for some cancers being better than ever, survivorship support must be built into every treatment plan from the start. Before treatment begins, healthcare providers should make time to talk about sometimes-overlooked key topics, such as reproductive options for people whose fertility may be affected by their cancer treatment, about plans for returning to work during or after treatment, and finding the right mental health support.
Where we can’t prevent cancer, both primary care providers and oncologists can work together to help patients receive the right diagnosis and treatment as quickly as possible. Knowing insurance coverage has a direct effect on how early cancer is caught, for example, younger people need support in understanding and accessing benefits and resources that may be available through their existing healthcare channels, like some employer-sponsored health plans. Even if getting treated for cancer is inevitable for some, taking immediate action to get screened when it’s appropriate is the best thing we can do to lessen the impact of these rising cancer incidences across the country. At the end of the day, being afraid of cancer doesn’t decrease the chances of getting sick or dying from it. Proactive screening and early detection do.
Brockman, Genetic Counselor, Color Health, Buffalo, New York, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Cancer is becoming more common in younger generations. Data show that people under 50 are experiencing higher rates of cancer than any generation before them. As a genetic counselor, I hoped these upward trends in early-onset malignancies would slow with a better understanding of risk factors and prevention strategies. Unfortunately, the opposite is happening. Recent findings from the American Cancer Society reveal that the incidence of at least 17 of 34 cancer types is rising among GenX and Millennials.
These statistics are alarming. I appreciate how easy it is for patients to get lost in the headlines about cancer, which may shape how they approach their healthcare. Each year, millions of Americans miss critical cancer screenings, with many citing fear of a positive test result as a leading reason. Others believe, despite the statistics, that cancer is not something they need to worry about until they are older. And then, of course, getting screened is not as easy as it should be.
In my work, I meet with people from both younger and older generations who have either faced cancer themselves or witnessed a loved one experience the disease. One of the most common sentiments I hear from these patients is the desire to catch cancer earlier. My answer is always this: The first and most important step everyone can take is understanding their risk.
For some, knowing they are at increased risk for cancer means starting screenings earlier — sometimes as early as age 25 — or getting screened with a more sensitive test.
This proactive approach is the right one. It also significantly reduces the burden of total and cancer-specific healthcare costs. While screening may carry some potential risks, clinicians can minimize these risks by adhering to evidence-based guidelines, such as those from the American Cancer Society, and ensuring there is appropriate discussion of treatment options when a diagnosis is made.
Normalizing Cancer Risk Assessment and Screening
A detailed cancer risk assessment and education about signs and symptoms should be part of every preventive care visit, regardless of someone’s age. Further, that cancer risk assessment should lead to clear recommendations and support for taking the next steps.
This is where care advocacy and patient navigation come in. Care advocacy can improve outcomes at every stage of the cancer journey, from increasing screening rates to improving quality of life for survivors. I’ve seen first-hand how care advocates help patients overcome hurdles like long wait times for appointments they need, making both screening and diagnostic care easier to access.
Now, with the finalization of a new rule from the Centers for Medicare & Medicaid Services, providers can bill for oncology navigation services that occur under their supervision. This formal recognition of care navigation affirms the value of these services not just clinically but financially as well. It will be through methods like care navigation, targeted outreach, and engaging educational resources — built into and covered by health plans — that patients will feel more in control over their health and have tools to help minimize the effects of cancer on the rest of their lives.
These services benefit healthcare providers as well. Care navigation supports clinical care teams, from primary care providers to oncologists, by ensuring patients are seen before their cancer progresses to a more advanced stage. And even if patients follow screening recommendations for the rest of their lives and never get a positive result, they’ve still gained something invaluable: peace of mind, knowing they’ve taken an active role in their health.
Fighting Fear With Routine
Treating cancer as a normal part of young people’s healthcare means helping them envision the disease as a condition that can be treated, much like a diagnosis of diabetes or high cholesterol. This mindset shift means quickly following up on a concerning symptom or screening result and reducing the time to start treatment if needed. And with treatment options and success rates for some cancers being better than ever, survivorship support must be built into every treatment plan from the start. Before treatment begins, healthcare providers should make time to talk about sometimes-overlooked key topics, such as reproductive options for people whose fertility may be affected by their cancer treatment, about plans for returning to work during or after treatment, and finding the right mental health support.
Where we can’t prevent cancer, both primary care providers and oncologists can work together to help patients receive the right diagnosis and treatment as quickly as possible. Knowing insurance coverage has a direct effect on how early cancer is caught, for example, younger people need support in understanding and accessing benefits and resources that may be available through their existing healthcare channels, like some employer-sponsored health plans. Even if getting treated for cancer is inevitable for some, taking immediate action to get screened when it’s appropriate is the best thing we can do to lessen the impact of these rising cancer incidences across the country. At the end of the day, being afraid of cancer doesn’t decrease the chances of getting sick or dying from it. Proactive screening and early detection do.
Brockman, Genetic Counselor, Color Health, Buffalo, New York, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Cancer is becoming more common in younger generations. Data show that people under 50 are experiencing higher rates of cancer than any generation before them. As a genetic counselor, I hoped these upward trends in early-onset malignancies would slow with a better understanding of risk factors and prevention strategies. Unfortunately, the opposite is happening. Recent findings from the American Cancer Society reveal that the incidence of at least 17 of 34 cancer types is rising among GenX and Millennials.
These statistics are alarming. I appreciate how easy it is for patients to get lost in the headlines about cancer, which may shape how they approach their healthcare. Each year, millions of Americans miss critical cancer screenings, with many citing fear of a positive test result as a leading reason. Others believe, despite the statistics, that cancer is not something they need to worry about until they are older. And then, of course, getting screened is not as easy as it should be.
In my work, I meet with people from both younger and older generations who have either faced cancer themselves or witnessed a loved one experience the disease. One of the most common sentiments I hear from these patients is the desire to catch cancer earlier. My answer is always this: The first and most important step everyone can take is understanding their risk.
For some, knowing they are at increased risk for cancer means starting screenings earlier — sometimes as early as age 25 — or getting screened with a more sensitive test.
This proactive approach is the right one. It also significantly reduces the burden of total and cancer-specific healthcare costs. While screening may carry some potential risks, clinicians can minimize these risks by adhering to evidence-based guidelines, such as those from the American Cancer Society, and ensuring there is appropriate discussion of treatment options when a diagnosis is made.
Normalizing Cancer Risk Assessment and Screening
A detailed cancer risk assessment and education about signs and symptoms should be part of every preventive care visit, regardless of someone’s age. Further, that cancer risk assessment should lead to clear recommendations and support for taking the next steps.
This is where care advocacy and patient navigation come in. Care advocacy can improve outcomes at every stage of the cancer journey, from increasing screening rates to improving quality of life for survivors. I’ve seen first-hand how care advocates help patients overcome hurdles like long wait times for appointments they need, making both screening and diagnostic care easier to access.
Now, with the finalization of a new rule from the Centers for Medicare & Medicaid Services, providers can bill for oncology navigation services that occur under their supervision. This formal recognition of care navigation affirms the value of these services not just clinically but financially as well. It will be through methods like care navigation, targeted outreach, and engaging educational resources — built into and covered by health plans — that patients will feel more in control over their health and have tools to help minimize the effects of cancer on the rest of their lives.
These services benefit healthcare providers as well. Care navigation supports clinical care teams, from primary care providers to oncologists, by ensuring patients are seen before their cancer progresses to a more advanced stage. And even if patients follow screening recommendations for the rest of their lives and never get a positive result, they’ve still gained something invaluable: peace of mind, knowing they’ve taken an active role in their health.
Fighting Fear With Routine
Treating cancer as a normal part of young people’s healthcare means helping them envision the disease as a condition that can be treated, much like a diagnosis of diabetes or high cholesterol. This mindset shift means quickly following up on a concerning symptom or screening result and reducing the time to start treatment if needed. And with treatment options and success rates for some cancers being better than ever, survivorship support must be built into every treatment plan from the start. Before treatment begins, healthcare providers should make time to talk about sometimes-overlooked key topics, such as reproductive options for people whose fertility may be affected by their cancer treatment, about plans for returning to work during or after treatment, and finding the right mental health support.
Where we can’t prevent cancer, both primary care providers and oncologists can work together to help patients receive the right diagnosis and treatment as quickly as possible. Knowing insurance coverage has a direct effect on how early cancer is caught, for example, younger people need support in understanding and accessing benefits and resources that may be available through their existing healthcare channels, like some employer-sponsored health plans. Even if getting treated for cancer is inevitable for some, taking immediate action to get screened when it’s appropriate is the best thing we can do to lessen the impact of these rising cancer incidences across the country. At the end of the day, being afraid of cancer doesn’t decrease the chances of getting sick or dying from it. Proactive screening and early detection do.
Brockman, Genetic Counselor, Color Health, Buffalo, New York, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Many Hurdles Exist to Treating Lung Cancer With CAR T Cells
These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.
“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.
He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.
Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.
Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.
He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”
A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
Identifying the Right Target
“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.
“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.
“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.
“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”
To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”
Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”
“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
A Question of Time
Another aspect of CAR T-cell therapy that is proving difficult is its delivery.
Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.
This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.
There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.
“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
Life-Threatening Toxicities
To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.
This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”
“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.
Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.
“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.
Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”
Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.
“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
‘At What Cost’ to Patients?
The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.
“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.
Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”
This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.
Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.
This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”
For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.
“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”
“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.
No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.
These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.
“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.
He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.
Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.
Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.
He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”
A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
Identifying the Right Target
“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.
“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.
“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.
“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”
To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”
Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”
“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
A Question of Time
Another aspect of CAR T-cell therapy that is proving difficult is its delivery.
Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.
This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.
There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.
“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
Life-Threatening Toxicities
To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.
This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”
“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.
Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.
“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.
Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”
Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.
“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
‘At What Cost’ to Patients?
The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.
“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.
Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”
This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.
Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.
This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”
For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.
“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”
“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.
No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.
These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.
“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.
He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.
Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.
Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.
He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”
A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
Identifying the Right Target
“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.
“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.
“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.
“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”
To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”
Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”
“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
A Question of Time
Another aspect of CAR T-cell therapy that is proving difficult is its delivery.
Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.
This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.
There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.
“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
Life-Threatening Toxicities
To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.
This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”
“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.
Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.
“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.
Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”
Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.
“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
‘At What Cost’ to Patients?
The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.
“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.
Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”
This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.
Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.
This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”
For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.
“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”
“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.
No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.
FROM WCLC 2024