Melanoma

TOPLINE:

Medicare Advantage plans had lower adjusted total resource use than traditional Medicare for patients with cancer undergoing chemotherapy, with no difference in 18-month survival between the two groups.

METHODOLOGY:

• Private Medicare Advantage plans enroll more than half of the Medicare population, but it is unknown if or how the cost restrictions they impose affect chemotherapy, which accounts for a large portion of cancer care costs.
• Researchers conducted a cohort study using national Medicare data from January 2015 to December 2019 to look at Medicare Advantage enrollment and treatment patterns for patients with cancer receiving chemotherapy.
• The study included 96,501 Medicare Advantage enrollees and 206,274 traditional Medicare beneficiaries who initiated chemotherapy between January 2016 and December 2019 (mean age, ~73 years; ~56% women; Hispanic individuals, 15% and 8%; Black individuals, 15% and 8%; and White individuals, 75% and 86%, respectively).
• Resource use and care quality were measured during a 6-month period following chemotherapy initiation, and survival days were measured 18 months after beginning chemotherapy.
• Resource use measures included hospital inpatient services, outpatient care, prescription drugs, hospice services, and chemotherapy services. Quality measures included chemotherapy-related emergency visits and hospital admissions, as well as avoidable emergency visits and preventable hospitalizations.

TAKEAWAY:

• Medicare Advantage plans had lower resource use than traditional Medicare per enrollee with cancer undergoing chemotherapy ($8718 lower; 95% CI, $8343-$9094).
• The lower resource use was largely caused by fewer chemotherapy visits and less expensive chemotherapy per visit in Medicare Advantage plans ($5032 lower; 95% CI, $4772-$5293).
• Medicare Advantage enrollees had 2.5 percentage points fewer chemotherapy-related emergency department visits and 0.7 percentage points fewer chemotherapy-related hospitalizations than traditional Medicare beneficiaries.
• There was no clinically meaningful difference in survival between Medicare Advantage and traditional Medicare beneficiaries during the 18 months following chemotherapy initiation.

IN PRACTICE:

“Our new finding is that MA [Medicare Advantage] plans had lower resource use than TM [traditional Medicare] among enrollees with cancer undergoing chemotherapy — a serious condition managed by specialists and requiring expensive treatments. This suggests that MA’s cost advantages over TM are not limited to conditions for which low-cost primary care management can avoid costly services,” the authors wrote.

SOURCE:

The study was led by Yamini Kalidindi, PhD, McDermott+ Consulting, Washington, DC. It was published online on September 20, 2024, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2024.34707), with a commentary.

LIMITATIONS:

The study’s findings may be affected by unobserved patient characteristics despite the use of inverse-probability weighting. The exclusion of Medicare Advantage enrollees in contracts with incomplete encounter data limits the generalizability of the results. The study does not apply to beneficiaries without Part D drug coverage. Quality measures were limited to those available from claims and encounter data, lacking information on patients’ cancer stage. The 18-month measure of survival might not adequately capture survival differences associated with early-stage cancers. The study did not measure whether patient care followed recommended guidelines.

DISCLOSURES:

Various authors reported grants from the National Institute on Aging, the National Institutes of Health, The Commonwealth Fund, Arnold Ventures, the National Cancer Institute, the Department of Defense, and the National Institute of Health Care Management. Additional disclosures are noted in the original article.

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

TOPLINE:

Medicare Advantage plans had lower adjusted total resource use than traditional Medicare for patients with cancer undergoing chemotherapy, with no difference in 18-month survival between the two groups.

METHODOLOGY:

• Private Medicare Advantage plans enroll more than half of the Medicare population, but it is unknown if or how the cost restrictions they impose affect chemotherapy, which accounts for a large portion of cancer care costs.
• Researchers conducted a cohort study using national Medicare data from January 2015 to December 2019 to look at Medicare Advantage enrollment and treatment patterns for patients with cancer receiving chemotherapy.
• The study included 96,501 Medicare Advantage enrollees and 206,274 traditional Medicare beneficiaries who initiated chemotherapy between January 2016 and December 2019 (mean age, ~73 years; ~56% women; Hispanic individuals, 15% and 8%; Black individuals, 15% and 8%; and White individuals, 75% and 86%, respectively).
• Resource use and care quality were measured during a 6-month period following chemotherapy initiation, and survival days were measured 18 months after beginning chemotherapy.
• Resource use measures included hospital inpatient services, outpatient care, prescription drugs, hospice services, and chemotherapy services. Quality measures included chemotherapy-related emergency visits and hospital admissions, as well as avoidable emergency visits and preventable hospitalizations.

TAKEAWAY:

• Medicare Advantage plans had lower resource use than traditional Medicare per enrollee with cancer undergoing chemotherapy ($8718 lower; 95% CI, $8343-$9094).
• The lower resource use was largely caused by fewer chemotherapy visits and less expensive chemotherapy per visit in Medicare Advantage plans ($5032 lower; 95% CI, $4772-$5293).
• Medicare Advantage enrollees had 2.5 percentage points fewer chemotherapy-related emergency department visits and 0.7 percentage points fewer chemotherapy-related hospitalizations than traditional Medicare beneficiaries.
• There was no clinically meaningful difference in survival between Medicare Advantage and traditional Medicare beneficiaries during the 18 months following chemotherapy initiation.

IN PRACTICE:

“Our new finding is that MA [Medicare Advantage] plans had lower resource use than TM [traditional Medicare] among enrollees with cancer undergoing chemotherapy — a serious condition managed by specialists and requiring expensive treatments. This suggests that MA’s cost advantages over TM are not limited to conditions for which low-cost primary care management can avoid costly services,” the authors wrote.

SOURCE:

The study was led by Yamini Kalidindi, PhD, McDermott+ Consulting, Washington, DC. It was published online on September 20, 2024, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2024.34707), with a commentary.

LIMITATIONS:

The study’s findings may be affected by unobserved patient characteristics despite the use of inverse-probability weighting. The exclusion of Medicare Advantage enrollees in contracts with incomplete encounter data limits the generalizability of the results. The study does not apply to beneficiaries without Part D drug coverage. Quality measures were limited to those available from claims and encounter data, lacking information on patients’ cancer stage. The 18-month measure of survival might not adequately capture survival differences associated with early-stage cancers. The study did not measure whether patient care followed recommended guidelines.

DISCLOSURES:

Various authors reported grants from the National Institute on Aging, the National Institutes of Health, The Commonwealth Fund, Arnold Ventures, the National Cancer Institute, the Department of Defense, and the National Institute of Health Care Management. Additional disclosures are noted in the original article.

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

TOPLINE:

Medicare Advantage plans had lower adjusted total resource use than traditional Medicare for patients with cancer undergoing chemotherapy, with no difference in 18-month survival between the two groups.

METHODOLOGY:

• Private Medicare Advantage plans enroll more than half of the Medicare population, but it is unknown if or how the cost restrictions they impose affect chemotherapy, which accounts for a large portion of cancer care costs.
• Researchers conducted a cohort study using national Medicare data from January 2015 to December 2019 to look at Medicare Advantage enrollment and treatment patterns for patients with cancer receiving chemotherapy.
• The study included 96,501 Medicare Advantage enrollees and 206,274 traditional Medicare beneficiaries who initiated chemotherapy between January 2016 and December 2019 (mean age, ~73 years; ~56% women; Hispanic individuals, 15% and 8%; Black individuals, 15% and 8%; and White individuals, 75% and 86%, respectively).
• Resource use and care quality were measured during a 6-month period following chemotherapy initiation, and survival days were measured 18 months after beginning chemotherapy.
• Resource use measures included hospital inpatient services, outpatient care, prescription drugs, hospice services, and chemotherapy services. Quality measures included chemotherapy-related emergency visits and hospital admissions, as well as avoidable emergency visits and preventable hospitalizations.

TAKEAWAY:

• Medicare Advantage plans had lower resource use than traditional Medicare per enrollee with cancer undergoing chemotherapy ($8718 lower; 95% CI, $8343-$9094).
• The lower resource use was largely caused by fewer chemotherapy visits and less expensive chemotherapy per visit in Medicare Advantage plans ($5032 lower; 95% CI, $4772-$5293).
• Medicare Advantage enrollees had 2.5 percentage points fewer chemotherapy-related emergency department visits and 0.7 percentage points fewer chemotherapy-related hospitalizations than traditional Medicare beneficiaries.
• There was no clinically meaningful difference in survival between Medicare Advantage and traditional Medicare beneficiaries during the 18 months following chemotherapy initiation.

IN PRACTICE:

“Our new finding is that MA [Medicare Advantage] plans had lower resource use than TM [traditional Medicare] among enrollees with cancer undergoing chemotherapy — a serious condition managed by specialists and requiring expensive treatments. This suggests that MA’s cost advantages over TM are not limited to conditions for which low-cost primary care management can avoid costly services,” the authors wrote.

SOURCE:

The study was led by Yamini Kalidindi, PhD, McDermott+ Consulting, Washington, DC. It was published online on September 20, 2024, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2024.34707), with a commentary.

LIMITATIONS:

The study’s findings may be affected by unobserved patient characteristics despite the use of inverse-probability weighting. The exclusion of Medicare Advantage enrollees in contracts with incomplete encounter data limits the generalizability of the results. The study does not apply to beneficiaries without Part D drug coverage. Quality measures were limited to those available from claims and encounter data, lacking information on patients’ cancer stage. The 18-month measure of survival might not adequately capture survival differences associated with early-stage cancers. The study did not measure whether patient care followed recommended guidelines.

DISCLOSURES:

Various authors reported grants from the National Institute on Aging, the National Institutes of Health, The Commonwealth Fund, Arnold Ventures, the National Cancer Institute, the Department of Defense, and the National Institute of Health Care Management. Additional disclosures are noted in the original article.

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

Despite the “remarkable progress” in cancer research and care, cancer remains “an ongoing public health challenge,” which requires significant attention and funding, according to the Cancer Progress Report 2024 from the American Association for Cancer Research (AACR).

The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted. 

One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.

These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
 

Inside the Report: Big Progress

Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives. 

According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.

The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.

“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.” 

The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.

“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
 

The Gaps

Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.

“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.

The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.

Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.

Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.

The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.

Financial toxicity remains prevalent as well.

The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.

For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.

On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
 

The Path Forward

Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.

“I am excited about what the future holds for cancer research, and especially for patient care,” she said. 

However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.

Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.

The AACR report specifically calls on Congress to:

• Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
• Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
• Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
• Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.

By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”

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

Despite the “remarkable progress” in cancer research and care, cancer remains “an ongoing public health challenge,” which requires significant attention and funding, according to the Cancer Progress Report 2024 from the American Association for Cancer Research (AACR).

The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted. 

One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.

These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
 

Inside the Report: Big Progress

Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives. 

According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.

The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.

“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.” 

The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.

“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
 

The Gaps

Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.

“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.

The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.

Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.

Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.

The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.

Financial toxicity remains prevalent as well.

The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.

For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.

On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
 

The Path Forward

Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.

“I am excited about what the future holds for cancer research, and especially for patient care,” she said. 

However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.

Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.

The AACR report specifically calls on Congress to:

• Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
• Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
• Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
• Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.

By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”

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

Despite the “remarkable progress” in cancer research and care, cancer remains “an ongoing public health challenge,” which requires significant attention and funding, according to the Cancer Progress Report 2024 from the American Association for Cancer Research (AACR).

The AACR’s 216-page report — an annual endeavor now in its 14th year — focused on the “tremendous” strides made in cancer care, prevention, and early detection and highlighted areas where more research and attention are warranted. 

One key area is funding. For the first time since 2016, federal funding for the National Institutes of Health (NIH) and National Cancer Institute (NCI) decreased in the past year. The cuts followed nearly a decade of funding increases that saw the NIH budget expand by nearly $15 billion, and that allowed for a “rapid pace and broad scope” of advances in cancer, AACR’s chief executive officer Margaret Foti, MD, PhD, said during a press briefing.

These recent cuts “threaten to curtail the medical progress seen in recent years and stymie future advancements,” said Dr. Foti, who called on Congress to commit to funding cancer research at significant and consistent levels to “maintain the momentum of progress against cancer.”
 

Inside the Report: Big Progress

Overall, advances in prevention, early detection, and treatment have helped catch more cancers earlier and save lives. 

According to the AACR report, the age-adjusted overall cancer death rate in the United States fell by 33% between 1991 and 2021, meaning about 4.1 million cancer deaths were averted. The overall cancer death rate for children and adolescents has declined by 24% in the past 2 decades. The 5-year relative survival rate for children diagnosed with cancer in the US has improved from 58% for those diagnosed in the mid-1970s to 85% for those diagnosed between 2013 and 2019.

The past fiscal year has seen many new approvals for cancer drugs, diagnostics, and screening tests. From July 1, 2023, to June 30, 2024, the Food and Drug Administration (FDA) approved 15 new anticancer therapeutics, as well as 15 new indications for previously approved agents, one new imaging agent, several artificial intelligence (AI) tools to improve early cancer detection and diagnosis, and two minimally invasive tests for assessing inherited cancer risk or early cancer detection, according to the report.

“Cancer diagnostics are becoming more sophisticated,” AACR president Patricia M. LoRusso, DO, PhD, said during the briefing. “New technologies, such as spatial transcriptomics, are helping us study tumors at a cellular level, and helping to unveil things that we did not initially even begin to understand or think of. AI-based approaches are beginning to transform cancer detection, diagnosis, clinical decision-making, and treatment response monitoring.” 

The report also highlights the significant progress in many childhood and adolescent/young adult cancers, Dr. LoRusso noted. These include FDA approvals for two new molecularly targeted therapeutics: tovorafenib for children with certain types of brain tumor and repotrectinib for children with a wide array of cancer types that have a specific genetic alteration known as NTRK gene fusion. It also includes an expanded approval for eflornithine to reduce the risk for relapse in children with high-risk neuroblastoma.

“Decades — decades — of basic research discoveries, have led to these clinical breakthroughs,” she stressed. “These gains against cancer are because of the rapid progress in our ability to decode the cancer genome, which has opened new and innovative avenues for drug development.”
 

The Gaps

Even with progress in cancer prevention, early detection, and treatment, cancer remains a significant issue.

“In 2024, it is estimated that more than 2 million new cases of cancer will be diagnosed in the United States. More than 611,000 people will die from the disease,” according to the report.

The 2024 report shows that incidence rates for some cancers are increasing in the United States, including vaccine-preventable cancers such as human papillomavirus (HPV)–associated oral cancers and, in young adults, cervical cancers. A recent analysis also found that overall cervical cancer incidence among women aged 30-34 years increased by 2.5% a year between 2012 and 2019.

Furthermore, despite clear evidence demonstrating that the HPV vaccine reduces cervical cancer incidence, uptake has remained poor, with only 38.6% of US children and adolescents aged 9-17 years receiving at least one dose of the vaccine in 2022.

Early-onset cancers are also increasing. Rates of breast, colorectal, and other cancers are on the rise in adults younger than 50 years, the report noted.

The report also pointed to data that 40% of all cancer cases in the United States can be attributed to preventable factors, such as smoking, excess body weight, and alcohol. However, our understanding of these risk factors has improved. Excessive levels of alcohol consumption have, for instance, been shown to increase the risk for six different types of cancer: certain types of head and neck cancer, esophageal squamous cell carcinoma, and breast, colorectal, liver, and stomach cancers.

Financial toxicity remains prevalent as well.

The report explains that financial hardship following a cancer diagnosis is widespread, and the effects can last for years. In fact, more than 40% of patients can spend their entire life savings within the first 2 years of cancer treatment. Among adult survivors of childhood cancers, 20.7% had trouble paying their medical bills, 29.9% said they had been sent to debt collection for unpaid bills, 14.1% had forgone medical care, and 26.8% could not afford nutritious meals.

For young cancer survivors, the lifetime costs associated with a diagnosis of cancer are substantial, reaching an average of $259,324 per person.

On a global level, it is estimated that from 2020 to 2050, the cumulative economic burden of cancer will be $25.2 trillion.
 

The Path Forward

Despite these challenges, Dr. LoRusso said, “it is unquestionable that we are in a time of unparalleled opportunities in cancer research.

“I am excited about what the future holds for cancer research, and especially for patient care,” she said. 

However, funding commitments are needed to avoid impeding this momentum and losing a “talented and creative young workforce” that has brought new ideas and new technologies to the table.

Continued robust funding will help “to markedly improve cancer care, increase cancer survivorship, spur economic growth, and maintain the United States’ position as the global leader in science and medical research,” she added.

The AACR report specifically calls on Congress to:

• Appropriate at least $51.3 billion in fiscal year 2025 for the base budget of the NIH and at least $7.934 billion for the NCI.
• Provide $3.6 billion in dedicated funding for Cancer Moonshot activities through fiscal year 2026 in addition to other funding, consistent with the President’s fiscal year 2025 budget.
• Appropriate at least $472.4 million in fiscal year 2025 for the CDC’s Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
• Allocate $55 million in funding for the Oncology Center of Excellence at FDA in fiscal year 2025 to provide regulators with the staff and tools necessary to conduct expedited review of cancer-related medical products.

By working together with Congress and other stakeholders, “we will be able to accelerate the pace of progress and make major strides toward the lifesaving goal of preventing and curing all cancers at the earliest possible time,” Dr. Foti said. “I believe if we do that ... one day we will win this war on cancer.”

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

BARCELONA, SPAIN — Patients with high-risk stage III resectable melanoma treated with neoadjuvant combination immunotherapy achieved higher event- and recurrence-free survival than patients who received monotherapy with immunotherapy or a targeted agent or targeted therapy plus immunotherapy, according to a large-scale pooled analysis from the International Neoadjuvant Melanoma Consortium.

Importantly, the analysis — presented at the annual meeting of the European Society for Medical Oncology — showed that achieving a major pathological response to neoadjuvant therapy is a key indicator of survival outcomes.

After 3 years of follow-up, the results showed that neoadjuvant therapy is not delaying melanoma recurrence, “it’s actually preventing it,” coinvestigator Hussein A. Tawbi, MD, PhD, Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, said in an interview. That’s “a big deal.”

Since 2010, the introduction of novel adjuvant and neoadjuvant therapies for high-risk stage III resectable melanoma has led to incremental gains for patients, said Georgina V. Long, MD, PhD, BSc, chair of Melanoma Medical Oncology and Translational Research at the University of Sydney in Australia, who presented the results.

The first pooled analysis of neoadjuvant therapy in 189 patients, published in 2021, indicated that those who achieved a major pathological response — defined as either a pathological complete response (with no remaining vital tumor) or a near-complete pathological response (with vital tumor ≤ 10%) — had the best recurrence-free survival rates.

In the current study, the researchers expanded their cohort to include 818 patients from 18 centers. Patients received at least one dose of neoadjuvant therapy — either combination immunotherapy, combination of targeted and immunotherapy agents, or monotherapy with either an immune checkpoint inhibitor or a targeted agent.

The median age was 59 years, and 38% of patients were women. The median follow-up so far is 38.8 months.

Overall, the 3-year event-free survival was 74% in patients who received any immunotherapy, 72% in those who received immunotherapy plus a targeted BRAF/MEK therapy, and just 37% in those who received targeted therapy alone. Similarly, 3-year recurrence-free survival rates were highest in patients who received immunotherapy at 77% vs 73% in those who received immunotherapy plus a targeted BRAF/MEK therapy and just 37% in those who received targeted therapy alone.

Looking specifically at progressive death 1 (PD-1)–based immunotherapy regimens, combination therapy led to a 3-year event-free survival rate between 77% and 95%, depending on the specific combinations, vs 64% with PD-1 monotherapy and 37% with combination targeted therapy.

Overall, patients who had a major pathological response were more likely to be recurrence free at 3 years. The 3-year recurrence-free survival was 88% in patients with a complete response, 68% in those with a partial pathological response, and 40% in those without a response.

Patients who received immunotherapy were more likely to have major pathological response. The 3-year recurrence-free survival was about 94% in patients who received combination or monotherapy with immune checkpoint inhibition, and about 87% in those who received immunotherapy plus targeted therapy. The recurrence-free survival rate was much lower in patients given only BRAF/MEK inhibitors.

The current overall survival data, which are still immature, suggested a few differences when stratifying the patients by treatment. Almost all patients with a major pathological response were alive at 3 years, compared with 86% of those with a partial pathological response and 70% of those without a pathological response.

Overall, the results showed that immunotherapy — as either combination or monotherapy — is “quite a bit” better than targeted therapy with BRAF/MEK agents, which offers no substantial benefit, said Dr. Twabi.

“When you see the same pattern happening in study after study, in a very clear, robust way, it actually becomes very powerful,” he explained.

Rebecca A. Dent, MD, MSc, chair of the ESMO Scientific Committee who was not involved in the study, told a press conference that the introduction of immunotherapy and combination immunotherapy has dramatically changed outcomes in melanoma.

Commenting on the current study results, Dr. Dent said that “combination immunotherapy is clearly showing exceptional stability in terms of long-term benefits.”

The question now is what are the toxicities and costs that come with combination immunotherapy, said Dr. Dent, from National Cancer Centre Singapore and Duke-NUS Medical School, Singapore.

No funding source was declared. Dr. Long declared relationships with a variety of companies, including AstraZeneca UK Limited, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, and Regeneron. Dr. Twabi declared relationships with Bristol-Myers Squibb, Novartis, Merck, Genentech, GlaxoSmithKline, Eisai, and others. Dr. Dent declared relationships with AstraZeneca, Roche, Eisai, Gilead Sciences, Eli Lilly, Merck, and Pfizer.

A version of this article appeared on Medscape.com.

BARCELONA, SPAIN — Patients with high-risk stage III resectable melanoma treated with neoadjuvant combination immunotherapy achieved higher event- and recurrence-free survival than patients who received monotherapy with immunotherapy or a targeted agent or targeted therapy plus immunotherapy, according to a large-scale pooled analysis from the International Neoadjuvant Melanoma Consortium.

Importantly, the analysis — presented at the annual meeting of the European Society for Medical Oncology — showed that achieving a major pathological response to neoadjuvant therapy is a key indicator of survival outcomes.

After 3 years of follow-up, the results showed that neoadjuvant therapy is not delaying melanoma recurrence, “it’s actually preventing it,” coinvestigator Hussein A. Tawbi, MD, PhD, Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, said in an interview. That’s “a big deal.”

Since 2010, the introduction of novel adjuvant and neoadjuvant therapies for high-risk stage III resectable melanoma has led to incremental gains for patients, said Georgina V. Long, MD, PhD, BSc, chair of Melanoma Medical Oncology and Translational Research at the University of Sydney in Australia, who presented the results.

The first pooled analysis of neoadjuvant therapy in 189 patients, published in 2021, indicated that those who achieved a major pathological response — defined as either a pathological complete response (with no remaining vital tumor) or a near-complete pathological response (with vital tumor ≤ 10%) — had the best recurrence-free survival rates.

In the current study, the researchers expanded their cohort to include 818 patients from 18 centers. Patients received at least one dose of neoadjuvant therapy — either combination immunotherapy, combination of targeted and immunotherapy agents, or monotherapy with either an immune checkpoint inhibitor or a targeted agent.

The median age was 59 years, and 38% of patients were women. The median follow-up so far is 38.8 months.

Overall, the 3-year event-free survival was 74% in patients who received any immunotherapy, 72% in those who received immunotherapy plus a targeted BRAF/MEK therapy, and just 37% in those who received targeted therapy alone. Similarly, 3-year recurrence-free survival rates were highest in patients who received immunotherapy at 77% vs 73% in those who received immunotherapy plus a targeted BRAF/MEK therapy and just 37% in those who received targeted therapy alone.

Looking specifically at progressive death 1 (PD-1)–based immunotherapy regimens, combination therapy led to a 3-year event-free survival rate between 77% and 95%, depending on the specific combinations, vs 64% with PD-1 monotherapy and 37% with combination targeted therapy.

Overall, patients who had a major pathological response were more likely to be recurrence free at 3 years. The 3-year recurrence-free survival was 88% in patients with a complete response, 68% in those with a partial pathological response, and 40% in those without a response.

Patients who received immunotherapy were more likely to have major pathological response. The 3-year recurrence-free survival was about 94% in patients who received combination or monotherapy with immune checkpoint inhibition, and about 87% in those who received immunotherapy plus targeted therapy. The recurrence-free survival rate was much lower in patients given only BRAF/MEK inhibitors.

The current overall survival data, which are still immature, suggested a few differences when stratifying the patients by treatment. Almost all patients with a major pathological response were alive at 3 years, compared with 86% of those with a partial pathological response and 70% of those without a pathological response.

Overall, the results showed that immunotherapy — as either combination or monotherapy — is “quite a bit” better than targeted therapy with BRAF/MEK agents, which offers no substantial benefit, said Dr. Twabi.

“When you see the same pattern happening in study after study, in a very clear, robust way, it actually becomes very powerful,” he explained.

Rebecca A. Dent, MD, MSc, chair of the ESMO Scientific Committee who was not involved in the study, told a press conference that the introduction of immunotherapy and combination immunotherapy has dramatically changed outcomes in melanoma.

Commenting on the current study results, Dr. Dent said that “combination immunotherapy is clearly showing exceptional stability in terms of long-term benefits.”

The question now is what are the toxicities and costs that come with combination immunotherapy, said Dr. Dent, from National Cancer Centre Singapore and Duke-NUS Medical School, Singapore.

No funding source was declared. Dr. Long declared relationships with a variety of companies, including AstraZeneca UK Limited, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, and Regeneron. Dr. Twabi declared relationships with Bristol-Myers Squibb, Novartis, Merck, Genentech, GlaxoSmithKline, Eisai, and others. Dr. Dent declared relationships with AstraZeneca, Roche, Eisai, Gilead Sciences, Eli Lilly, Merck, and Pfizer.

A version of this article appeared on Medscape.com.

BARCELONA, SPAIN — Patients with high-risk stage III resectable melanoma treated with neoadjuvant combination immunotherapy achieved higher event- and recurrence-free survival than patients who received monotherapy with immunotherapy or a targeted agent or targeted therapy plus immunotherapy, according to a large-scale pooled analysis from the International Neoadjuvant Melanoma Consortium.

Importantly, the analysis — presented at the annual meeting of the European Society for Medical Oncology — showed that achieving a major pathological response to neoadjuvant therapy is a key indicator of survival outcomes.

After 3 years of follow-up, the results showed that neoadjuvant therapy is not delaying melanoma recurrence, “it’s actually preventing it,” coinvestigator Hussein A. Tawbi, MD, PhD, Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, said in an interview. That’s “a big deal.”

Since 2010, the introduction of novel adjuvant and neoadjuvant therapies for high-risk stage III resectable melanoma has led to incremental gains for patients, said Georgina V. Long, MD, PhD, BSc, chair of Melanoma Medical Oncology and Translational Research at the University of Sydney in Australia, who presented the results.

The first pooled analysis of neoadjuvant therapy in 189 patients, published in 2021, indicated that those who achieved a major pathological response — defined as either a pathological complete response (with no remaining vital tumor) or a near-complete pathological response (with vital tumor ≤ 10%) — had the best recurrence-free survival rates.

In the current study, the researchers expanded their cohort to include 818 patients from 18 centers. Patients received at least one dose of neoadjuvant therapy — either combination immunotherapy, combination of targeted and immunotherapy agents, or monotherapy with either an immune checkpoint inhibitor or a targeted agent.

The median age was 59 years, and 38% of patients were women. The median follow-up so far is 38.8 months.

Overall, the 3-year event-free survival was 74% in patients who received any immunotherapy, 72% in those who received immunotherapy plus a targeted BRAF/MEK therapy, and just 37% in those who received targeted therapy alone. Similarly, 3-year recurrence-free survival rates were highest in patients who received immunotherapy at 77% vs 73% in those who received immunotherapy plus a targeted BRAF/MEK therapy and just 37% in those who received targeted therapy alone.

Looking specifically at progressive death 1 (PD-1)–based immunotherapy regimens, combination therapy led to a 3-year event-free survival rate between 77% and 95%, depending on the specific combinations, vs 64% with PD-1 monotherapy and 37% with combination targeted therapy.

Overall, patients who had a major pathological response were more likely to be recurrence free at 3 years. The 3-year recurrence-free survival was 88% in patients with a complete response, 68% in those with a partial pathological response, and 40% in those without a response.

Patients who received immunotherapy were more likely to have major pathological response. The 3-year recurrence-free survival was about 94% in patients who received combination or monotherapy with immune checkpoint inhibition, and about 87% in those who received immunotherapy plus targeted therapy. The recurrence-free survival rate was much lower in patients given only BRAF/MEK inhibitors.

The current overall survival data, which are still immature, suggested a few differences when stratifying the patients by treatment. Almost all patients with a major pathological response were alive at 3 years, compared with 86% of those with a partial pathological response and 70% of those without a pathological response.

Overall, the results showed that immunotherapy — as either combination or monotherapy — is “quite a bit” better than targeted therapy with BRAF/MEK agents, which offers no substantial benefit, said Dr. Twabi.

“When you see the same pattern happening in study after study, in a very clear, robust way, it actually becomes very powerful,” he explained.

Rebecca A. Dent, MD, MSc, chair of the ESMO Scientific Committee who was not involved in the study, told a press conference that the introduction of immunotherapy and combination immunotherapy has dramatically changed outcomes in melanoma.

Commenting on the current study results, Dr. Dent said that “combination immunotherapy is clearly showing exceptional stability in terms of long-term benefits.”

The question now is what are the toxicities and costs that come with combination immunotherapy, said Dr. Dent, from National Cancer Centre Singapore and Duke-NUS Medical School, Singapore.

No funding source was declared. Dr. Long declared relationships with a variety of companies, including AstraZeneca UK Limited, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, and Regeneron. Dr. Twabi declared relationships with Bristol-Myers Squibb, Novartis, Merck, Genentech, GlaxoSmithKline, Eisai, and others. Dr. Dent declared relationships with AstraZeneca, Roche, Eisai, Gilead Sciences, Eli Lilly, Merck, and Pfizer.

A version of this article appeared on Medscape.com.

Pesticides have transformed modern agriculture by boosting production yields and helping alleviate food insecurity amid rapid global population growth. However, from a public health perspective, exposure to pesticides has been linked to numerous harmful effects, including neurologic disorders like Parkinson’s disease, weakened immune function, and an increased risk for cancer.

Pesticide exposure has been associated with cancers such as colorectal cancer, lung cancer, leukemia (in children and adults), lymphoma, and pancreatic cancer. But these studies primarily have focused on specific groups of individuals with known exposure to certain pesticides or cancer types, thus offering a limited perspective.

A comprehensive assessment of how pesticide use affects cancer risk across a broader population has yet to be conducted.

A recent population-level study aimed to address this gap by evaluating cancer risks in the US population using a model that accounts for pesticide use and adjusts for various factors. The goal was to identify regional disparities in exposure and contribute to the development of public health policies that protect populations from potential harm.
 

Calculating Cancer Risk

Researchers developed a model using several data sources to estimate the additional cancer risk from agricultural pesticide use. Key data included:

• Pesticide use data from the US Geological Survey in 2019, which covered 69 agricultural pesticides across 3143 counties
• Cancer incidence rates per 100,000 people, which were collected between 2015 and 2019 by the National Institutes of Health and the Centers for Disease Control and Prevention; these data covered various cancers, including bladder, colorectal, leukemia, lung, non-Hodgkin lymphoma, and pancreatic cancers
• Covariates, including smoking prevalence, the Social Vulnerability Index, agricultural land use, and total US population in 2019

Pesticide use profile patterns were developed using latent class analysis, a statistical method used to identify homogeneous subgroups within a heterogeneous population. A generalized linear model then estimated how these pesticide use patterns and the covariates affected cancer incidence.

The model highlighted regions with the highest and lowest “additional” cancer risks linked to pesticide exposure, calculating the estimated increase in cancer cases per year that resulted from variations in agricultural pesticide use.
 

Midwest Most Affected

While this model doesn’t establish causality or assess individual risk, it reveals regional trends in the association between pesticide use patterns and cancer incidence from a population-based perspective.

The Midwest, known for its high corn production, emerged as the region most affected by pesticide use. Compared with regions with the lowest risk, the Midwest faced an additional 154,541 cancer cases annually across all types. For colorectal and pancreatic cancers, the yearly increases were 20,927 and 3835 cases, respectively. Similar trends were observed for leukemia and non-Hodgkin lymphoma.
 

Pesticides vs Smoking

The researchers also estimated the additional cancer risk related to smoking, using the same model. They found that pesticides contributed to a higher risk for cancer than smoking in several cases.

The most significant difference was observed with non-Hodgkin lymphoma, where pesticides were linked to 154.1% more cases than smoking. For all cancers combined, as well as bladder cancer and leukemia, the increases were moderate: 18.7%, 19.3%, and 21.0%, respectively.

This result highlights the importance of considering pesticide exposure alongside smoking when studying cancer risks.
 

Expanding Scope of Research

Some limitations of this study should be noted. Certain counties lacked complete data, and there was heterogeneity in the size and population of the counties studied. The research also did not account for seasonal and migrant workers, who are likely to be heavily exposed. In addition, the data used in the study were not independently validated, and they could not be used to assess individual risk.

The effect of pesticides on human health is a vast and critical field of research, often focusing on a limited range of pesticides or specific cancers. This study stands out by taking a broader, more holistic approach, aiming to highlight regional inequalities and identify less-studied pesticides that could be future research priorities.

Given the significant public health impact, the authors encouraged the authorities to share these findings with the most vulnerable communities to raise awareness.
 

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

Pesticides have transformed modern agriculture by boosting production yields and helping alleviate food insecurity amid rapid global population growth. However, from a public health perspective, exposure to pesticides has been linked to numerous harmful effects, including neurologic disorders like Parkinson’s disease, weakened immune function, and an increased risk for cancer.

Pesticide exposure has been associated with cancers such as colorectal cancer, lung cancer, leukemia (in children and adults), lymphoma, and pancreatic cancer. But these studies primarily have focused on specific groups of individuals with known exposure to certain pesticides or cancer types, thus offering a limited perspective.

A comprehensive assessment of how pesticide use affects cancer risk across a broader population has yet to be conducted.

A recent population-level study aimed to address this gap by evaluating cancer risks in the US population using a model that accounts for pesticide use and adjusts for various factors. The goal was to identify regional disparities in exposure and contribute to the development of public health policies that protect populations from potential harm.
 

Calculating Cancer Risk

Researchers developed a model using several data sources to estimate the additional cancer risk from agricultural pesticide use. Key data included:

• Pesticide use data from the US Geological Survey in 2019, which covered 69 agricultural pesticides across 3143 counties
• Cancer incidence rates per 100,000 people, which were collected between 2015 and 2019 by the National Institutes of Health and the Centers for Disease Control and Prevention; these data covered various cancers, including bladder, colorectal, leukemia, lung, non-Hodgkin lymphoma, and pancreatic cancers
• Covariates, including smoking prevalence, the Social Vulnerability Index, agricultural land use, and total US population in 2019

Pesticide use profile patterns were developed using latent class analysis, a statistical method used to identify homogeneous subgroups within a heterogeneous population. A generalized linear model then estimated how these pesticide use patterns and the covariates affected cancer incidence.

The model highlighted regions with the highest and lowest “additional” cancer risks linked to pesticide exposure, calculating the estimated increase in cancer cases per year that resulted from variations in agricultural pesticide use.
 

Midwest Most Affected

While this model doesn’t establish causality or assess individual risk, it reveals regional trends in the association between pesticide use patterns and cancer incidence from a population-based perspective.

The Midwest, known for its high corn production, emerged as the region most affected by pesticide use. Compared with regions with the lowest risk, the Midwest faced an additional 154,541 cancer cases annually across all types. For colorectal and pancreatic cancers, the yearly increases were 20,927 and 3835 cases, respectively. Similar trends were observed for leukemia and non-Hodgkin lymphoma.
 

Pesticides vs Smoking

The researchers also estimated the additional cancer risk related to smoking, using the same model. They found that pesticides contributed to a higher risk for cancer than smoking in several cases.

The most significant difference was observed with non-Hodgkin lymphoma, where pesticides were linked to 154.1% more cases than smoking. For all cancers combined, as well as bladder cancer and leukemia, the increases were moderate: 18.7%, 19.3%, and 21.0%, respectively.

This result highlights the importance of considering pesticide exposure alongside smoking when studying cancer risks.
 

Expanding Scope of Research

Some limitations of this study should be noted. Certain counties lacked complete data, and there was heterogeneity in the size and population of the counties studied. The research also did not account for seasonal and migrant workers, who are likely to be heavily exposed. In addition, the data used in the study were not independently validated, and they could not be used to assess individual risk.

The effect of pesticides on human health is a vast and critical field of research, often focusing on a limited range of pesticides or specific cancers. This study stands out by taking a broader, more holistic approach, aiming to highlight regional inequalities and identify less-studied pesticides that could be future research priorities.

Given the significant public health impact, the authors encouraged the authorities to share these findings with the most vulnerable communities to raise awareness.
 

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

Pesticides have transformed modern agriculture by boosting production yields and helping alleviate food insecurity amid rapid global population growth. However, from a public health perspective, exposure to pesticides has been linked to numerous harmful effects, including neurologic disorders like Parkinson’s disease, weakened immune function, and an increased risk for cancer.

Pesticide exposure has been associated with cancers such as colorectal cancer, lung cancer, leukemia (in children and adults), lymphoma, and pancreatic cancer. But these studies primarily have focused on specific groups of individuals with known exposure to certain pesticides or cancer types, thus offering a limited perspective.

A comprehensive assessment of how pesticide use affects cancer risk across a broader population has yet to be conducted.

A recent population-level study aimed to address this gap by evaluating cancer risks in the US population using a model that accounts for pesticide use and adjusts for various factors. The goal was to identify regional disparities in exposure and contribute to the development of public health policies that protect populations from potential harm.
 

Calculating Cancer Risk

Researchers developed a model using several data sources to estimate the additional cancer risk from agricultural pesticide use. Key data included:

• Pesticide use data from the US Geological Survey in 2019, which covered 69 agricultural pesticides across 3143 counties
• Cancer incidence rates per 100,000 people, which were collected between 2015 and 2019 by the National Institutes of Health and the Centers for Disease Control and Prevention; these data covered various cancers, including bladder, colorectal, leukemia, lung, non-Hodgkin lymphoma, and pancreatic cancers
• Covariates, including smoking prevalence, the Social Vulnerability Index, agricultural land use, and total US population in 2019

Pesticide use profile patterns were developed using latent class analysis, a statistical method used to identify homogeneous subgroups within a heterogeneous population. A generalized linear model then estimated how these pesticide use patterns and the covariates affected cancer incidence.

The model highlighted regions with the highest and lowest “additional” cancer risks linked to pesticide exposure, calculating the estimated increase in cancer cases per year that resulted from variations in agricultural pesticide use.
 

Midwest Most Affected

While this model doesn’t establish causality or assess individual risk, it reveals regional trends in the association between pesticide use patterns and cancer incidence from a population-based perspective.

The Midwest, known for its high corn production, emerged as the region most affected by pesticide use. Compared with regions with the lowest risk, the Midwest faced an additional 154,541 cancer cases annually across all types. For colorectal and pancreatic cancers, the yearly increases were 20,927 and 3835 cases, respectively. Similar trends were observed for leukemia and non-Hodgkin lymphoma.
 

Pesticides vs Smoking

The researchers also estimated the additional cancer risk related to smoking, using the same model. They found that pesticides contributed to a higher risk for cancer than smoking in several cases.

The most significant difference was observed with non-Hodgkin lymphoma, where pesticides were linked to 154.1% more cases than smoking. For all cancers combined, as well as bladder cancer and leukemia, the increases were moderate: 18.7%, 19.3%, and 21.0%, respectively.

This result highlights the importance of considering pesticide exposure alongside smoking when studying cancer risks.
 

Expanding Scope of Research

Some limitations of this study should be noted. Certain counties lacked complete data, and there was heterogeneity in the size and population of the counties studied. The research also did not account for seasonal and migrant workers, who are likely to be heavily exposed. In addition, the data used in the study were not independently validated, and they could not be used to assess individual risk.

The effect of pesticides on human health is a vast and critical field of research, often focusing on a limited range of pesticides or specific cancers. This study stands out by taking a broader, more holistic approach, aiming to highlight regional inequalities and identify less-studied pesticides that could be future research priorities.

Given the significant public health impact, the authors encouraged the authorities to share these findings with the most vulnerable communities to raise awareness.
 

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

The Food and Drug Administration (FDA) has approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza, Genentech) as a subcutaneous injection in adults, covering all approved indications of the intravenous (IV) formulation.

Approved indications include non–small cell lung cancer (NSCLC), SCLC, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma. Specific indications are available with the full prescribing information at Drugs@FDA.

This is the first programmed death–ligand 1 inhibitor to gain approval for subcutaneous administration.

“This approval represents a significant option to improve the patient experience,” Ann Fish-Steagall, RN, Senior Vice President of Patient Services at the LUNGevity Foundation stated in a Genentech press release.

Subcutaneous atezolizumab and hyaluronidase-tqjs was evaluated in the open-label, randomized IMscin001 trial of 371 adult patients with locally advanced or metastatic NSCLC who were not previously exposed to cancer immunotherapy and who had disease progression following treatment with platinum-based chemotherapy. Patients were randomized 2:1 to receive subcutaneous or IV administration until disease progression or unacceptable toxicity.

Atezolizumab exposure, the primary outcome measure of the study, met the lower limit of geometric mean ratio above the prespecified threshold of 0.8 (cycle 1C trough, 1.05; area under the curve for days 0-21, 0.87).

No notable differences were observed in overall response rate, progression-free survival, or overall survival between the two formulations, according to the FDA approval notice.

The confirmed overall response rate was 9% in the subcutaneous arm and 8% intravenous arm.

Adverse events of any grade occurring in at least 10% of patients were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

The recommended dose for subcutaneous injection is one 15 mL injection, which contains 1875 mg of atezolizumab and 30,000 units of hyaluronidase.

Injections should be administered in the thigh over approximately 7 minutes every 3 weeks. By contrast, IV administration generally takes 30-60 minutes.

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

The Food and Drug Administration (FDA) has approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza, Genentech) as a subcutaneous injection in adults, covering all approved indications of the intravenous (IV) formulation.

Approved indications include non–small cell lung cancer (NSCLC), SCLC, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma. Specific indications are available with the full prescribing information at Drugs@FDA.

This is the first programmed death–ligand 1 inhibitor to gain approval for subcutaneous administration.

“This approval represents a significant option to improve the patient experience,” Ann Fish-Steagall, RN, Senior Vice President of Patient Services at the LUNGevity Foundation stated in a Genentech press release.

Subcutaneous atezolizumab and hyaluronidase-tqjs was evaluated in the open-label, randomized IMscin001 trial of 371 adult patients with locally advanced or metastatic NSCLC who were not previously exposed to cancer immunotherapy and who had disease progression following treatment with platinum-based chemotherapy. Patients were randomized 2:1 to receive subcutaneous or IV administration until disease progression or unacceptable toxicity.

Atezolizumab exposure, the primary outcome measure of the study, met the lower limit of geometric mean ratio above the prespecified threshold of 0.8 (cycle 1C trough, 1.05; area under the curve for days 0-21, 0.87).

No notable differences were observed in overall response rate, progression-free survival, or overall survival between the two formulations, according to the FDA approval notice.

The confirmed overall response rate was 9% in the subcutaneous arm and 8% intravenous arm.

Adverse events of any grade occurring in at least 10% of patients were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

The recommended dose for subcutaneous injection is one 15 mL injection, which contains 1875 mg of atezolizumab and 30,000 units of hyaluronidase.

Injections should be administered in the thigh over approximately 7 minutes every 3 weeks. By contrast, IV administration generally takes 30-60 minutes.

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

The Food and Drug Administration (FDA) has approved atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza, Genentech) as a subcutaneous injection in adults, covering all approved indications of the intravenous (IV) formulation.

Approved indications include non–small cell lung cancer (NSCLC), SCLC, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma. Specific indications are available with the full prescribing information at Drugs@FDA.

This is the first programmed death–ligand 1 inhibitor to gain approval for subcutaneous administration.

“This approval represents a significant option to improve the patient experience,” Ann Fish-Steagall, RN, Senior Vice President of Patient Services at the LUNGevity Foundation stated in a Genentech press release.

Subcutaneous atezolizumab and hyaluronidase-tqjs was evaluated in the open-label, randomized IMscin001 trial of 371 adult patients with locally advanced or metastatic NSCLC who were not previously exposed to cancer immunotherapy and who had disease progression following treatment with platinum-based chemotherapy. Patients were randomized 2:1 to receive subcutaneous or IV administration until disease progression or unacceptable toxicity.

Atezolizumab exposure, the primary outcome measure of the study, met the lower limit of geometric mean ratio above the prespecified threshold of 0.8 (cycle 1C trough, 1.05; area under the curve for days 0-21, 0.87).

No notable differences were observed in overall response rate, progression-free survival, or overall survival between the two formulations, according to the FDA approval notice.

The confirmed overall response rate was 9% in the subcutaneous arm and 8% intravenous arm.

Adverse events of any grade occurring in at least 10% of patients were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite.

The recommended dose for subcutaneous injection is one 15 mL injection, which contains 1875 mg of atezolizumab and 30,000 units of hyaluronidase.

Injections should be administered in the thigh over approximately 7 minutes every 3 weeks. By contrast, IV administration generally takes 30-60 minutes.

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

Background

Melanoma is a malignant type of skin cancer and is the fifth most common type of cancer in the United States. The purpose of this study is to determine how demographic information such as race and gender may influence mortality rates in melanoma patients. To date, no previous studies have analyzed epidemiological trends in melanoma mortality using the CDC Wonder database. However, previous literature has suggested that non-Hispanic Whites have the highest mortality rate.

Methods

CDC Wonder is a database that contains mortality and demographic information for various pathologies. Melanoma cases were specified using the ICD-10 code C43. Patients over the age of 35 were considered for this study. Mortality rates were generated based on gender, race, and a combination of both variables. Data analysis involved finding the rates and 95% confidence intervals for the crude and age-adjusted mortality rate (AAMR) per 100,000. Joinpoint regression analysis was also used.

Results

Several differences in the age-adjusted mortality rate were observed. In every year from 1999 to 2022, the non-Hispanic White group (NH White) had the highest mortality rate, whereas all other races had similar rates. Meanwhile, when stratifying by both race and gender, it appears that NH White males have the highest rate in mortality. In 2022, the mortality rate for NH White males was 8.8 per 100,000, whereas the second highest rate belonged to the NH White female group (4 per 100,000). All other racial and gender combinations had similar mortality rates. The trends in mortality rates did not fluctuate much from the years 1999-2022. No significant deviation in mortality trends were seen after the start of the COVID-19 pandemic.

Conclusions

This data corroborates with the results from previous studies. It also indicates that certain demographics that may be at greater risk for mortality, and that the mortality rates have remained relatively stable. The mortality rate for melanoma may vary by race and gender. More specifically, NH White males may be susceptible to higher mortality rates compared to other demographic groups. Future research on cancer staging and treatment modality received could help explain these differences.

Background

Melanoma is a malignant type of skin cancer and is the fifth most common type of cancer in the United States. The purpose of this study is to determine how demographic information such as race and gender may influence mortality rates in melanoma patients. To date, no previous studies have analyzed epidemiological trends in melanoma mortality using the CDC Wonder database. However, previous literature has suggested that non-Hispanic Whites have the highest mortality rate.

Methods

CDC Wonder is a database that contains mortality and demographic information for various pathologies. Melanoma cases were specified using the ICD-10 code C43. Patients over the age of 35 were considered for this study. Mortality rates were generated based on gender, race, and a combination of both variables. Data analysis involved finding the rates and 95% confidence intervals for the crude and age-adjusted mortality rate (AAMR) per 100,000. Joinpoint regression analysis was also used.

Results

Several differences in the age-adjusted mortality rate were observed. In every year from 1999 to 2022, the non-Hispanic White group (NH White) had the highest mortality rate, whereas all other races had similar rates. Meanwhile, when stratifying by both race and gender, it appears that NH White males have the highest rate in mortality. In 2022, the mortality rate for NH White males was 8.8 per 100,000, whereas the second highest rate belonged to the NH White female group (4 per 100,000). All other racial and gender combinations had similar mortality rates. The trends in mortality rates did not fluctuate much from the years 1999-2022. No significant deviation in mortality trends were seen after the start of the COVID-19 pandemic.

Conclusions

This data corroborates with the results from previous studies. It also indicates that certain demographics that may be at greater risk for mortality, and that the mortality rates have remained relatively stable. The mortality rate for melanoma may vary by race and gender. More specifically, NH White males may be susceptible to higher mortality rates compared to other demographic groups. Future research on cancer staging and treatment modality received could help explain these differences.

Background

Melanoma is a malignant type of skin cancer and is the fifth most common type of cancer in the United States. The purpose of this study is to determine how demographic information such as race and gender may influence mortality rates in melanoma patients. To date, no previous studies have analyzed epidemiological trends in melanoma mortality using the CDC Wonder database. However, previous literature has suggested that non-Hispanic Whites have the highest mortality rate.

Methods

CDC Wonder is a database that contains mortality and demographic information for various pathologies. Melanoma cases were specified using the ICD-10 code C43. Patients over the age of 35 were considered for this study. Mortality rates were generated based on gender, race, and a combination of both variables. Data analysis involved finding the rates and 95% confidence intervals for the crude and age-adjusted mortality rate (AAMR) per 100,000. Joinpoint regression analysis was also used.

Results

Several differences in the age-adjusted mortality rate were observed. In every year from 1999 to 2022, the non-Hispanic White group (NH White) had the highest mortality rate, whereas all other races had similar rates. Meanwhile, when stratifying by both race and gender, it appears that NH White males have the highest rate in mortality. In 2022, the mortality rate for NH White males was 8.8 per 100,000, whereas the second highest rate belonged to the NH White female group (4 per 100,000). All other racial and gender combinations had similar mortality rates. The trends in mortality rates did not fluctuate much from the years 1999-2022. No significant deviation in mortality trends were seen after the start of the COVID-19 pandemic.

Conclusions

This data corroborates with the results from previous studies. It also indicates that certain demographics that may be at greater risk for mortality, and that the mortality rates have remained relatively stable. The mortality rate for melanoma may vary by race and gender. More specifically, NH White males may be susceptible to higher mortality rates compared to other demographic groups. Future research on cancer staging and treatment modality received could help explain these differences.

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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