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Combo Therapy Prolongs Survival in Gastric Cancer Patients, Regardless of PD-L1 Expression
, according to a new study.
Jiafu Ji, MD, PhD, presented this and other findings of the randomized, double-blind, placebo-controlled phase 3 COMPASSION-15 trial at the annual meeting of the American Association for Cancer Research (AACR).
“The consistent survival benefits across all prespecified PD-L1 expression cutoffs, particularly in patients with low PD-L1 expression, have significant implications for clinical practice by expanding treatment options, improving outcomes for patients with PD-L1–low tumors, influencing guidelines, and stimulating further research in advanced G/GEJ adenocarcinoma treatment,” said Dr. Ji, a principal investigator of this trial, in an interview.
Unmet Need
The incidence of gastric cancer is particularly high in China, but as Dr. Ji discussed in his talk, the treatment options for patients with advanced disease remain limited. Although the Food and Drug Administration (FDA) has approved the combination of PD-L1 inhibitors with chemotherapy for the first-line treatment of advanced gastric cancer, not all patients respond to the treatment, explained Dr. Ji, who is a professor of gastrointestinal surgery and president of Peking University Cancer Hospital and Beijing Institute for Cancer Research in China.
He added that the combination of PD-L1 inhibitors and chemotherapy has not yet been approved for the treatment of advanced gastric cancer in China, leaving chemotherapy as the only treatment option for Chinese patients.
Study Design
To evaluate the efficacy and safety of first-line cadonilimab plus standard chemotherapy in patients with advanced or metastatic gastric cancer, the authors of the COMPASSION-15 trial enrolled 610 patients with unresectable, locally advanced, or metastatic G/GEJ adenocarcinoma who had not received any prior treatments. PD-L1 expression status was not used to exclude patients from the trial.
In a press conference held at AACR 2024, Dr. Ji explained the study rationale, design, and endpoints. He said that patients with tumors without PD-L1 expression typically show little to no benefit from anti–PD-1/PD-L1 inhibitors, and their treatment options are limited to chemotherapy.
“Testing the efficacy of this bispecific antibody in this patient population could provide an alternative treatment approach for them,” he added.
Patients were randomized 1:1 to receive either cadonilimab (10 mg/kg every 3 weeks) plus chemotherapy or placebo plus chemotherapy. The primary endpoint of the study was overall survival (OS) in the intent-to-treat (ITT) population, and secondary efficacy endpoints included OS, progression-free survival (PFS), and objective response rate (ORR) in the ITT population, as well as in patients stratified by PD-L1 expression.
Cadonilimab Plus Standard Chemotherapy Improves OS
Interim analysis, conducted with a median follow-up of 18.69 months, showed a significant improvement in OS for the cadonilimab plus chemotherapy group compared with the chemotherapy-alone group, according to data presented at the press conference. The median OS was 15.0 months in the cadonilimab group versus 10.8 months in the placebo group, representing a 38% reduction in the risk of death (hazard ratio [HR], 0.62; 95% CI, 0.50-0.78, P < .001).
Yelena Y. Janjigian, MD, who not involved in COMPASSION-15, provided critique of the study, during another session at the meeting, in which she discussed the CheckMate 649 trial. She noted that, although the median OS of 15 months in the COMPASSION-15 study was slightly higher than the OS in the CheckMate 649 trial (approximately 14 months), comparing the results of two studies is challenging.
“In the COMPASSION-15 trial, chemotherapy was stopped after [4.5 months], and only 50% of patients received chemotherapy with subsequent treatment — this is not standard and may limit the comparison with other immunotherapy trials,” explained Dr. Janjigian, who is a gastrointestinal oncologist and was a principal investigator in the phase 3 CheckMate 649 immunotherapy trial for advanced gastric cancer.
Importantly, survival benefit with cadonilimab plus chemotherapy was observed across all prespecified PD-L1 expression levels, including in patients with low PD-L1 expression (PD-L1 combined positive score [CPS] less than 5%). In the low PD-L1 expression group (CPS less than 5%), the median OS was 14.8 months in the cadonilimab group compared with 11.8 months in the placebo group (HR, 0.70; 95% CI, 0.51-0.95; P = .011).
“These positive survival outcomes when cadonilimab was combined with chemotherapy may be attributed to synergistic mechanisms of action, enhanced immune responses, modulation of the tumor microenvironment, and careful patient selection based on biomarker assessments,” noted Dr. Ji, during an interview. “Targeting multiple pathways using bispecific antibodies provides potential synergistic effects, enhancing anti-tumor activity and improving treatment outcomes.”
Cadonilimab Plus Standard Chemotherapy Reduces the Risk of Tumor Progression
In addition to prolonging OS, cadonilimab plus chemotherapy also provided superior PFS and ORR compared to placebo plus chemotherapy.
The median PFS was 7.0 months in the cadonilimab plus chemotherapy group, versus 5.3 months in the chemotherapy-only group (HR, 0.53; 95% CI, 0.44-0.65, P < .001), and the ORR was 65.2% versus 48.9%, respectively. Furthermore, the duration of response was longer with cadonilimab plus chemotherapy than with placebo plus chemotherapy (8.8 versus 4.4 months, respectively).
Toxicities Associated With Cadonilimab Plus Standard Chemotherapy Are Manageable
The safety profile of the cadonilimab plus chemotherapy regimen was manageable, with grade 3 or higher treatment-related adverse events occurring in 71.8% of patients in the cadonilimab group and 60.5% of patients in the placebo group. No new safety signals were observed.
During an interview, Dr. Ji said that the most common adverse events were endocrine toxicity, skin toxicity, and lung toxicity. “These adverse events were managed through close monitoring, symptom management, and appropriate interventions based on the severity and nature of the toxicity experienced by patients,” he explained. He added that this toxicity profile of cadonilimab is similar to the toxicity profiles of approved PD-1 and CTLA-4 inhibitors.
Implications — A New Treatment Paradigm for Advanced Gastric Cancer?
According to Dr. Ji, the interim results from the cadonilimab study suggest that this novel PD-1/CTLA-4 bispecific antibody, in combination with chemotherapy, could become a new standard first-line treatment option for patients with advanced G/GEJ adenocarcinoma, offering a significant survival advantage over chemotherapy alone, regardless of PD-L1 status.
“The ability of cadonilimab to improve survival outcomes, regardless of PD-L1 status, is a significant advancement, as we have struggled to find effective treatments for patients with low PD-L1 expression in this setting,” he said, during the interview.
Despite these promising findings, Dr. Janjigian highlighted that patient stratification in the COMPASSION-15 study is currently lacking. She explained that biomarkers such as MSI status, T-reg signatures, and HER-2 are important to consider according to data from the CheckMate 649 trial.
“Hazard ratios for patients with T-reg–high tumors were almost 0.6, independent of inflammatory status. These data suggest that we can maybe even cure some patients with PD-1/CTLA-4 inhibitors,” she noted.
She added that knowing the status of MSI and HER-2 is clinically important as it can inform clinicians whether they can avoid chemotherapy or add trastuzumab.
“Despite the suboptimal comparator arm, the study is very important and offers a rationale for dual PD-1/CTLA-4 blockade,” Dr. Janjigian concluded.
COMPASSION-15 was funded by Akeso Biopharma, Inc. Dr. Ji reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients. Dr. Janjigian lists relationships with AbbVie, AmerisourceBergen Drug Corporation, Arcus Biosciences, Ask-Gene Pharma, Inc., Astellas Pharma, AstraZeneca, Basilea Pharmaceutica Ltd., Bayer, Bristol Myers, Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck, Pfizer, and many other companies, as well as the U.S. Department of Defense, National Cancer Institute, and others.
, according to a new study.
Jiafu Ji, MD, PhD, presented this and other findings of the randomized, double-blind, placebo-controlled phase 3 COMPASSION-15 trial at the annual meeting of the American Association for Cancer Research (AACR).
“The consistent survival benefits across all prespecified PD-L1 expression cutoffs, particularly in patients with low PD-L1 expression, have significant implications for clinical practice by expanding treatment options, improving outcomes for patients with PD-L1–low tumors, influencing guidelines, and stimulating further research in advanced G/GEJ adenocarcinoma treatment,” said Dr. Ji, a principal investigator of this trial, in an interview.
Unmet Need
The incidence of gastric cancer is particularly high in China, but as Dr. Ji discussed in his talk, the treatment options for patients with advanced disease remain limited. Although the Food and Drug Administration (FDA) has approved the combination of PD-L1 inhibitors with chemotherapy for the first-line treatment of advanced gastric cancer, not all patients respond to the treatment, explained Dr. Ji, who is a professor of gastrointestinal surgery and president of Peking University Cancer Hospital and Beijing Institute for Cancer Research in China.
He added that the combination of PD-L1 inhibitors and chemotherapy has not yet been approved for the treatment of advanced gastric cancer in China, leaving chemotherapy as the only treatment option for Chinese patients.
Study Design
To evaluate the efficacy and safety of first-line cadonilimab plus standard chemotherapy in patients with advanced or metastatic gastric cancer, the authors of the COMPASSION-15 trial enrolled 610 patients with unresectable, locally advanced, or metastatic G/GEJ adenocarcinoma who had not received any prior treatments. PD-L1 expression status was not used to exclude patients from the trial.
In a press conference held at AACR 2024, Dr. Ji explained the study rationale, design, and endpoints. He said that patients with tumors without PD-L1 expression typically show little to no benefit from anti–PD-1/PD-L1 inhibitors, and their treatment options are limited to chemotherapy.
“Testing the efficacy of this bispecific antibody in this patient population could provide an alternative treatment approach for them,” he added.
Patients were randomized 1:1 to receive either cadonilimab (10 mg/kg every 3 weeks) plus chemotherapy or placebo plus chemotherapy. The primary endpoint of the study was overall survival (OS) in the intent-to-treat (ITT) population, and secondary efficacy endpoints included OS, progression-free survival (PFS), and objective response rate (ORR) in the ITT population, as well as in patients stratified by PD-L1 expression.
Cadonilimab Plus Standard Chemotherapy Improves OS
Interim analysis, conducted with a median follow-up of 18.69 months, showed a significant improvement in OS for the cadonilimab plus chemotherapy group compared with the chemotherapy-alone group, according to data presented at the press conference. The median OS was 15.0 months in the cadonilimab group versus 10.8 months in the placebo group, representing a 38% reduction in the risk of death (hazard ratio [HR], 0.62; 95% CI, 0.50-0.78, P < .001).
Yelena Y. Janjigian, MD, who not involved in COMPASSION-15, provided critique of the study, during another session at the meeting, in which she discussed the CheckMate 649 trial. She noted that, although the median OS of 15 months in the COMPASSION-15 study was slightly higher than the OS in the CheckMate 649 trial (approximately 14 months), comparing the results of two studies is challenging.
“In the COMPASSION-15 trial, chemotherapy was stopped after [4.5 months], and only 50% of patients received chemotherapy with subsequent treatment — this is not standard and may limit the comparison with other immunotherapy trials,” explained Dr. Janjigian, who is a gastrointestinal oncologist and was a principal investigator in the phase 3 CheckMate 649 immunotherapy trial for advanced gastric cancer.
Importantly, survival benefit with cadonilimab plus chemotherapy was observed across all prespecified PD-L1 expression levels, including in patients with low PD-L1 expression (PD-L1 combined positive score [CPS] less than 5%). In the low PD-L1 expression group (CPS less than 5%), the median OS was 14.8 months in the cadonilimab group compared with 11.8 months in the placebo group (HR, 0.70; 95% CI, 0.51-0.95; P = .011).
“These positive survival outcomes when cadonilimab was combined with chemotherapy may be attributed to synergistic mechanisms of action, enhanced immune responses, modulation of the tumor microenvironment, and careful patient selection based on biomarker assessments,” noted Dr. Ji, during an interview. “Targeting multiple pathways using bispecific antibodies provides potential synergistic effects, enhancing anti-tumor activity and improving treatment outcomes.”
Cadonilimab Plus Standard Chemotherapy Reduces the Risk of Tumor Progression
In addition to prolonging OS, cadonilimab plus chemotherapy also provided superior PFS and ORR compared to placebo plus chemotherapy.
The median PFS was 7.0 months in the cadonilimab plus chemotherapy group, versus 5.3 months in the chemotherapy-only group (HR, 0.53; 95% CI, 0.44-0.65, P < .001), and the ORR was 65.2% versus 48.9%, respectively. Furthermore, the duration of response was longer with cadonilimab plus chemotherapy than with placebo plus chemotherapy (8.8 versus 4.4 months, respectively).
Toxicities Associated With Cadonilimab Plus Standard Chemotherapy Are Manageable
The safety profile of the cadonilimab plus chemotherapy regimen was manageable, with grade 3 or higher treatment-related adverse events occurring in 71.8% of patients in the cadonilimab group and 60.5% of patients in the placebo group. No new safety signals were observed.
During an interview, Dr. Ji said that the most common adverse events were endocrine toxicity, skin toxicity, and lung toxicity. “These adverse events were managed through close monitoring, symptom management, and appropriate interventions based on the severity and nature of the toxicity experienced by patients,” he explained. He added that this toxicity profile of cadonilimab is similar to the toxicity profiles of approved PD-1 and CTLA-4 inhibitors.
Implications — A New Treatment Paradigm for Advanced Gastric Cancer?
According to Dr. Ji, the interim results from the cadonilimab study suggest that this novel PD-1/CTLA-4 bispecific antibody, in combination with chemotherapy, could become a new standard first-line treatment option for patients with advanced G/GEJ adenocarcinoma, offering a significant survival advantage over chemotherapy alone, regardless of PD-L1 status.
“The ability of cadonilimab to improve survival outcomes, regardless of PD-L1 status, is a significant advancement, as we have struggled to find effective treatments for patients with low PD-L1 expression in this setting,” he said, during the interview.
Despite these promising findings, Dr. Janjigian highlighted that patient stratification in the COMPASSION-15 study is currently lacking. She explained that biomarkers such as MSI status, T-reg signatures, and HER-2 are important to consider according to data from the CheckMate 649 trial.
“Hazard ratios for patients with T-reg–high tumors were almost 0.6, independent of inflammatory status. These data suggest that we can maybe even cure some patients with PD-1/CTLA-4 inhibitors,” she noted.
She added that knowing the status of MSI and HER-2 is clinically important as it can inform clinicians whether they can avoid chemotherapy or add trastuzumab.
“Despite the suboptimal comparator arm, the study is very important and offers a rationale for dual PD-1/CTLA-4 blockade,” Dr. Janjigian concluded.
COMPASSION-15 was funded by Akeso Biopharma, Inc. Dr. Ji reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients. Dr. Janjigian lists relationships with AbbVie, AmerisourceBergen Drug Corporation, Arcus Biosciences, Ask-Gene Pharma, Inc., Astellas Pharma, AstraZeneca, Basilea Pharmaceutica Ltd., Bayer, Bristol Myers, Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck, Pfizer, and many other companies, as well as the U.S. Department of Defense, National Cancer Institute, and others.
, according to a new study.
Jiafu Ji, MD, PhD, presented this and other findings of the randomized, double-blind, placebo-controlled phase 3 COMPASSION-15 trial at the annual meeting of the American Association for Cancer Research (AACR).
“The consistent survival benefits across all prespecified PD-L1 expression cutoffs, particularly in patients with low PD-L1 expression, have significant implications for clinical practice by expanding treatment options, improving outcomes for patients with PD-L1–low tumors, influencing guidelines, and stimulating further research in advanced G/GEJ adenocarcinoma treatment,” said Dr. Ji, a principal investigator of this trial, in an interview.
Unmet Need
The incidence of gastric cancer is particularly high in China, but as Dr. Ji discussed in his talk, the treatment options for patients with advanced disease remain limited. Although the Food and Drug Administration (FDA) has approved the combination of PD-L1 inhibitors with chemotherapy for the first-line treatment of advanced gastric cancer, not all patients respond to the treatment, explained Dr. Ji, who is a professor of gastrointestinal surgery and president of Peking University Cancer Hospital and Beijing Institute for Cancer Research in China.
He added that the combination of PD-L1 inhibitors and chemotherapy has not yet been approved for the treatment of advanced gastric cancer in China, leaving chemotherapy as the only treatment option for Chinese patients.
Study Design
To evaluate the efficacy and safety of first-line cadonilimab plus standard chemotherapy in patients with advanced or metastatic gastric cancer, the authors of the COMPASSION-15 trial enrolled 610 patients with unresectable, locally advanced, or metastatic G/GEJ adenocarcinoma who had not received any prior treatments. PD-L1 expression status was not used to exclude patients from the trial.
In a press conference held at AACR 2024, Dr. Ji explained the study rationale, design, and endpoints. He said that patients with tumors without PD-L1 expression typically show little to no benefit from anti–PD-1/PD-L1 inhibitors, and their treatment options are limited to chemotherapy.
“Testing the efficacy of this bispecific antibody in this patient population could provide an alternative treatment approach for them,” he added.
Patients were randomized 1:1 to receive either cadonilimab (10 mg/kg every 3 weeks) plus chemotherapy or placebo plus chemotherapy. The primary endpoint of the study was overall survival (OS) in the intent-to-treat (ITT) population, and secondary efficacy endpoints included OS, progression-free survival (PFS), and objective response rate (ORR) in the ITT population, as well as in patients stratified by PD-L1 expression.
Cadonilimab Plus Standard Chemotherapy Improves OS
Interim analysis, conducted with a median follow-up of 18.69 months, showed a significant improvement in OS for the cadonilimab plus chemotherapy group compared with the chemotherapy-alone group, according to data presented at the press conference. The median OS was 15.0 months in the cadonilimab group versus 10.8 months in the placebo group, representing a 38% reduction in the risk of death (hazard ratio [HR], 0.62; 95% CI, 0.50-0.78, P < .001).
Yelena Y. Janjigian, MD, who not involved in COMPASSION-15, provided critique of the study, during another session at the meeting, in which she discussed the CheckMate 649 trial. She noted that, although the median OS of 15 months in the COMPASSION-15 study was slightly higher than the OS in the CheckMate 649 trial (approximately 14 months), comparing the results of two studies is challenging.
“In the COMPASSION-15 trial, chemotherapy was stopped after [4.5 months], and only 50% of patients received chemotherapy with subsequent treatment — this is not standard and may limit the comparison with other immunotherapy trials,” explained Dr. Janjigian, who is a gastrointestinal oncologist and was a principal investigator in the phase 3 CheckMate 649 immunotherapy trial for advanced gastric cancer.
Importantly, survival benefit with cadonilimab plus chemotherapy was observed across all prespecified PD-L1 expression levels, including in patients with low PD-L1 expression (PD-L1 combined positive score [CPS] less than 5%). In the low PD-L1 expression group (CPS less than 5%), the median OS was 14.8 months in the cadonilimab group compared with 11.8 months in the placebo group (HR, 0.70; 95% CI, 0.51-0.95; P = .011).
“These positive survival outcomes when cadonilimab was combined with chemotherapy may be attributed to synergistic mechanisms of action, enhanced immune responses, modulation of the tumor microenvironment, and careful patient selection based on biomarker assessments,” noted Dr. Ji, during an interview. “Targeting multiple pathways using bispecific antibodies provides potential synergistic effects, enhancing anti-tumor activity and improving treatment outcomes.”
Cadonilimab Plus Standard Chemotherapy Reduces the Risk of Tumor Progression
In addition to prolonging OS, cadonilimab plus chemotherapy also provided superior PFS and ORR compared to placebo plus chemotherapy.
The median PFS was 7.0 months in the cadonilimab plus chemotherapy group, versus 5.3 months in the chemotherapy-only group (HR, 0.53; 95% CI, 0.44-0.65, P < .001), and the ORR was 65.2% versus 48.9%, respectively. Furthermore, the duration of response was longer with cadonilimab plus chemotherapy than with placebo plus chemotherapy (8.8 versus 4.4 months, respectively).
Toxicities Associated With Cadonilimab Plus Standard Chemotherapy Are Manageable
The safety profile of the cadonilimab plus chemotherapy regimen was manageable, with grade 3 or higher treatment-related adverse events occurring in 71.8% of patients in the cadonilimab group and 60.5% of patients in the placebo group. No new safety signals were observed.
During an interview, Dr. Ji said that the most common adverse events were endocrine toxicity, skin toxicity, and lung toxicity. “These adverse events were managed through close monitoring, symptom management, and appropriate interventions based on the severity and nature of the toxicity experienced by patients,” he explained. He added that this toxicity profile of cadonilimab is similar to the toxicity profiles of approved PD-1 and CTLA-4 inhibitors.
Implications — A New Treatment Paradigm for Advanced Gastric Cancer?
According to Dr. Ji, the interim results from the cadonilimab study suggest that this novel PD-1/CTLA-4 bispecific antibody, in combination with chemotherapy, could become a new standard first-line treatment option for patients with advanced G/GEJ adenocarcinoma, offering a significant survival advantage over chemotherapy alone, regardless of PD-L1 status.
“The ability of cadonilimab to improve survival outcomes, regardless of PD-L1 status, is a significant advancement, as we have struggled to find effective treatments for patients with low PD-L1 expression in this setting,” he said, during the interview.
Despite these promising findings, Dr. Janjigian highlighted that patient stratification in the COMPASSION-15 study is currently lacking. She explained that biomarkers such as MSI status, T-reg signatures, and HER-2 are important to consider according to data from the CheckMate 649 trial.
“Hazard ratios for patients with T-reg–high tumors were almost 0.6, independent of inflammatory status. These data suggest that we can maybe even cure some patients with PD-1/CTLA-4 inhibitors,” she noted.
She added that knowing the status of MSI and HER-2 is clinically important as it can inform clinicians whether they can avoid chemotherapy or add trastuzumab.
“Despite the suboptimal comparator arm, the study is very important and offers a rationale for dual PD-1/CTLA-4 blockade,” Dr. Janjigian concluded.
COMPASSION-15 was funded by Akeso Biopharma, Inc. Dr. Ji reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients. Dr. Janjigian lists relationships with AbbVie, AmerisourceBergen Drug Corporation, Arcus Biosciences, Ask-Gene Pharma, Inc., Astellas Pharma, AstraZeneca, Basilea Pharmaceutica Ltd., Bayer, Bristol Myers, Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck, Pfizer, and many other companies, as well as the U.S. Department of Defense, National Cancer Institute, and others.
FROM AACR 2024
FDA Expands Enhertu Indication to HER2-Positive Solid Tumors
The agent had already been approved for several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer as well as adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.
The current accelerated approval is the first tumor-agnostic approval of a HER2-directed therapy and antibody drug conjugate.
“Until approval of trastuzumab deruxtecan, patients with metastatic HER2-positive tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston, said in an AstraZeneca press statement. “Based on the clinically meaningful response rates across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”
Approval was based on findings in 192 patients enrolled in either the DESTINY-PanTumor02 trial, the DESTINY-Lung01 trial, or the DESTINY-CRC02 trial. Patients in the multicenter trials underwent treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.
Confirmed objective response rates were 51.4%, 52.9%, and 46.9% in the three studies, respectively. Median duration of response was 19.4, 6.9, and 5.5 months, respectively.
The most common adverse reactions occurring in at least 20% of patients included decreased white blood cell count, hemoglobin, lymphocyte count, and neutrophil count, as well as nausea, fatigue, platelet count, vomiting, alopecia, diarrhea, stomatitis, and upper respiratory tract infection.
Full prescribing information includes a boxed warning about the risk for interstitial lung disease and embryo-fetal toxicity.
The recommended dosage is 5.4 mg/kg given as an intravenous infusion one every 3 weeks until disease progression or unacceptable toxicity.
A version of this article appeared on Medscape.com.
The agent had already been approved for several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer as well as adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.
The current accelerated approval is the first tumor-agnostic approval of a HER2-directed therapy and antibody drug conjugate.
“Until approval of trastuzumab deruxtecan, patients with metastatic HER2-positive tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston, said in an AstraZeneca press statement. “Based on the clinically meaningful response rates across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”
Approval was based on findings in 192 patients enrolled in either the DESTINY-PanTumor02 trial, the DESTINY-Lung01 trial, or the DESTINY-CRC02 trial. Patients in the multicenter trials underwent treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.
Confirmed objective response rates were 51.4%, 52.9%, and 46.9% in the three studies, respectively. Median duration of response was 19.4, 6.9, and 5.5 months, respectively.
The most common adverse reactions occurring in at least 20% of patients included decreased white blood cell count, hemoglobin, lymphocyte count, and neutrophil count, as well as nausea, fatigue, platelet count, vomiting, alopecia, diarrhea, stomatitis, and upper respiratory tract infection.
Full prescribing information includes a boxed warning about the risk for interstitial lung disease and embryo-fetal toxicity.
The recommended dosage is 5.4 mg/kg given as an intravenous infusion one every 3 weeks until disease progression or unacceptable toxicity.
A version of this article appeared on Medscape.com.
The agent had already been approved for several cancer types, including certain patients with unresectable or metastatic HER2-positive breast cancer as well as adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had received a prior trastuzumab-based regimen.
The current accelerated approval is the first tumor-agnostic approval of a HER2-directed therapy and antibody drug conjugate.
“Until approval of trastuzumab deruxtecan, patients with metastatic HER2-positive tumors have had limited treatment options,” Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at the University of Texas MD Anderson Cancer Center, Houston, said in an AstraZeneca press statement. “Based on the clinically meaningful response rates across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”
Approval was based on findings in 192 patients enrolled in either the DESTINY-PanTumor02 trial, the DESTINY-Lung01 trial, or the DESTINY-CRC02 trial. Patients in the multicenter trials underwent treatment until disease progression, death, withdrawal of consent or unacceptable toxicity.
Confirmed objective response rates were 51.4%, 52.9%, and 46.9% in the three studies, respectively. Median duration of response was 19.4, 6.9, and 5.5 months, respectively.
The most common adverse reactions occurring in at least 20% of patients included decreased white blood cell count, hemoglobin, lymphocyte count, and neutrophil count, as well as nausea, fatigue, platelet count, vomiting, alopecia, diarrhea, stomatitis, and upper respiratory tract infection.
Full prescribing information includes a boxed warning about the risk for interstitial lung disease and embryo-fetal toxicity.
The recommended dosage is 5.4 mg/kg given as an intravenous infusion one every 3 weeks until disease progression or unacceptable toxicity.
A version of this article appeared on Medscape.com.
New Trials in Prostate Cancer: Could Your Patient Benefit?
Metastatic castration-sensitive prostate cancer
Adults with this diagnosis may be interested in a randomized, double-blind, phase 3 study examining whether an experimental poly (ADP-ribose) polymerase (PARP) inhibitor called saruparib can further delay disease progression when added to a next-generation hormonal agent such as abiraterone (Zytiga), darolutamide (Nubeqa), or enzalutamide (Xtandi).
One group of participants will take daily oral doses of saruparib plus physician’s choice of a next-generation hormonal agent until disease progression or another reason for stopping therapy. The other group will add a placebo to a next-generation hormonal agent.
Sites in Rhode Island, Arkansas, California, Michigan, Australia, Canada, Japan, Taiwan, Thailand, the United Kingdom, and South Korea began seeking the trial’s 1800 participants in November 2023. Research centers in 31 other US states and 18 other countries are gearing up. The primary endpoint is radiographic progression-free survival. Overall survival and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov.
This news organization asked Marc Garnick, MD, professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, for his take on the trial. “The study is interesting since it is adding to the evaluations of continued intensification for first-line therapy and will help further elucidate the role of PARP inhibition regardless of homologous repair status,” Dr. Garnick said. “Plus, saruparib is supposedly more selective on PARP1, which in-and-of-itself is of potential benefit.”
Metastatic castration-resistant prostate cancer
People with this type of cancer who have progressed on a next-generation hormonal agent may be eligible for a randomized, open-label, phase 3 trial testing an investigational oral treatment called MK-5684 to see if it increases survival more effectively than switching to an alternative next-generation hormonal agent.
MK-5684 is designed to inhibit the CYP11A1 enzyme, thereby disrupting the androgen-receptor signaling pathway.
One group will take twice-daily tablets of MK-5684 plus hormone replacement therapy, oral dexamethasone, and oral fludrocortisone acetate (Florinef), with rescue hydrocortisone as needed. The other participants will take daily tablets of a next-generation hormonal agent: Either enzalutamide or abiraterone. Patients assigned to abiraterone will also be given prednisone tablets.
US-based sites in nine states and Puerto Rico started looking for the trial’s 1500 participants in December 2023 in partnership with study centers in Australia, Israel, South Korea, and Taiwan. The primary endpoints are radiographic progression-free survival and overall survival. QoL will not be tracked. More details at clinicaltrials.gov.
Metastatic castration-resistant prostate cancer
Patients in this situation who have progressed on taxane-based chemotherapy as well as a next-generation hormonal agent have the option to enroll in another phase 3 MK-5684 study.
Like the trial described above, all patients will remain on their respective therapy until disease progression. In this trial, one group will take twice-daily tablets of MK-5684 without hormone replacement therapy but the same mix of oral dexamethasone and fludrocortisone. Rescue hydrocortisone will also be available. The second group will be assigned either enzalutamide or abiraterone plus prednisone.
Sites in Puerto Rico, Colorado, Nevada, and Virginia, and five other countries outside the United States, opened their doors to the first of 1200 patients in December 2023. The primary endpoints are radiographic progression-free survival and overall survival, analyzed separately for patients with and without an androgen receptor ligand-binding domain mutation. QoL will not be measured. More details at clinicaltrials.gov.
High-risk prostate cancer
People with this diagnosis can join a randomized, open-label, phase 3 National Cancer Institute study to test whether stereotactic body radiation therapy (SBRT) is as effective as conventional external beam radiation therapy (EBRT) at preventing metastasis.
SBRT delivers radiation to tumors with higher precision than EBRT. The advantage of SBRT is the ability to deliver fewer doses over a shorter duration with less collateral damage to surrounding tissues.
In the trial, half of participants will undergo five treatments of SBRT over 2 weeks, while the other half will receive 20-45 treatments of EBRT over 4-9 weeks. Study sites in 14 US states began recruiting the trial’s 1209 participants in November 2023. Metastasis-free survival over 15 years is the primary endpoint, overall survival is a secondary endpoint, and QoL measures, apart from fatigue, will not be tracked. More details at clinicaltrials.gov.
Dr. Garnick viewed this study as “problematic because patient accrual ends in 2036 with a readout in 2041.” He added, “What its relevance will be at that time is unlikely to provide practice changes, since in that interval there will undoubtedly be multiple advances in place.”
Newly diagnosed favorable intermediate risk prostate cancer
People with this type of cancer are eligible for an open-label, phase 4 real-world study of a radioactive diagnostic agent called piflufolastat F 18 (Pylarify) that targets prostate-specific membrane antigen (PSMA)–positive lesions. Piflufolastat is designed to enhance detection of metastases during PSMA-targeted PET.
Participants will receive a single injection of piflufolastat followed 1-2 hours later by a single whole-body PET-CT or PET-MRI scan. A study site at the Hoag Cancer Center in Irvine, California, welcomed the first of the trial’s 274 participants in February 2024. Sites in Tower Urology, Los Angeles, and the Cleveland Clinic, Ohio, are gearing up. Detection rate is the primary endpoint. Overall survival and QoL are not measured. More details at clinicaltrials.gov
Stages I-IV prostate cancer without bone metastases. People 60 years or older with this type of prostate cancer who are just starting androgen deprivation therapy are eligible for a phase 3, placebo-controlled trial investigating whether high-dose vitamin D can prevent or reduce androgen-deprivation therapy-induced bone loss.
For 1 year, participants will take tablets of high-dose vitamin D or a placebo and then undergo dual x-ray absorptiometry. The Ochsner Medical Center in Jefferson, Louisiana, started recruiting 366 trial participants in December 2023. Reduction in bone mineral density loss in the hip and spine over 1 year is the primary objective. QoL is a secondary objective, and overall survival will not be measured. More details at clinicaltrials.gov
Dr. Garnick expressed some concerns with the trial design so far, including that “the dose of vitamin D is not delineated nor is the target vitamin D level.”
All trial information is from the National Institutes of Health’s National Library of Medicine (online at clinicaltrials.gov). Dr. Garnick did not report conflicts with any of the trials.
A version of this article appeared on Medscape.com.
Metastatic castration-sensitive prostate cancer
Adults with this diagnosis may be interested in a randomized, double-blind, phase 3 study examining whether an experimental poly (ADP-ribose) polymerase (PARP) inhibitor called saruparib can further delay disease progression when added to a next-generation hormonal agent such as abiraterone (Zytiga), darolutamide (Nubeqa), or enzalutamide (Xtandi).
One group of participants will take daily oral doses of saruparib plus physician’s choice of a next-generation hormonal agent until disease progression or another reason for stopping therapy. The other group will add a placebo to a next-generation hormonal agent.
Sites in Rhode Island, Arkansas, California, Michigan, Australia, Canada, Japan, Taiwan, Thailand, the United Kingdom, and South Korea began seeking the trial’s 1800 participants in November 2023. Research centers in 31 other US states and 18 other countries are gearing up. The primary endpoint is radiographic progression-free survival. Overall survival and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov.
This news organization asked Marc Garnick, MD, professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, for his take on the trial. “The study is interesting since it is adding to the evaluations of continued intensification for first-line therapy and will help further elucidate the role of PARP inhibition regardless of homologous repair status,” Dr. Garnick said. “Plus, saruparib is supposedly more selective on PARP1, which in-and-of-itself is of potential benefit.”
Metastatic castration-resistant prostate cancer
People with this type of cancer who have progressed on a next-generation hormonal agent may be eligible for a randomized, open-label, phase 3 trial testing an investigational oral treatment called MK-5684 to see if it increases survival more effectively than switching to an alternative next-generation hormonal agent.
MK-5684 is designed to inhibit the CYP11A1 enzyme, thereby disrupting the androgen-receptor signaling pathway.
One group will take twice-daily tablets of MK-5684 plus hormone replacement therapy, oral dexamethasone, and oral fludrocortisone acetate (Florinef), with rescue hydrocortisone as needed. The other participants will take daily tablets of a next-generation hormonal agent: Either enzalutamide or abiraterone. Patients assigned to abiraterone will also be given prednisone tablets.
US-based sites in nine states and Puerto Rico started looking for the trial’s 1500 participants in December 2023 in partnership with study centers in Australia, Israel, South Korea, and Taiwan. The primary endpoints are radiographic progression-free survival and overall survival. QoL will not be tracked. More details at clinicaltrials.gov.
Metastatic castration-resistant prostate cancer
Patients in this situation who have progressed on taxane-based chemotherapy as well as a next-generation hormonal agent have the option to enroll in another phase 3 MK-5684 study.
Like the trial described above, all patients will remain on their respective therapy until disease progression. In this trial, one group will take twice-daily tablets of MK-5684 without hormone replacement therapy but the same mix of oral dexamethasone and fludrocortisone. Rescue hydrocortisone will also be available. The second group will be assigned either enzalutamide or abiraterone plus prednisone.
Sites in Puerto Rico, Colorado, Nevada, and Virginia, and five other countries outside the United States, opened their doors to the first of 1200 patients in December 2023. The primary endpoints are radiographic progression-free survival and overall survival, analyzed separately for patients with and without an androgen receptor ligand-binding domain mutation. QoL will not be measured. More details at clinicaltrials.gov.
High-risk prostate cancer
People with this diagnosis can join a randomized, open-label, phase 3 National Cancer Institute study to test whether stereotactic body radiation therapy (SBRT) is as effective as conventional external beam radiation therapy (EBRT) at preventing metastasis.
SBRT delivers radiation to tumors with higher precision than EBRT. The advantage of SBRT is the ability to deliver fewer doses over a shorter duration with less collateral damage to surrounding tissues.
In the trial, half of participants will undergo five treatments of SBRT over 2 weeks, while the other half will receive 20-45 treatments of EBRT over 4-9 weeks. Study sites in 14 US states began recruiting the trial’s 1209 participants in November 2023. Metastasis-free survival over 15 years is the primary endpoint, overall survival is a secondary endpoint, and QoL measures, apart from fatigue, will not be tracked. More details at clinicaltrials.gov.
Dr. Garnick viewed this study as “problematic because patient accrual ends in 2036 with a readout in 2041.” He added, “What its relevance will be at that time is unlikely to provide practice changes, since in that interval there will undoubtedly be multiple advances in place.”
Newly diagnosed favorable intermediate risk prostate cancer
People with this type of cancer are eligible for an open-label, phase 4 real-world study of a radioactive diagnostic agent called piflufolastat F 18 (Pylarify) that targets prostate-specific membrane antigen (PSMA)–positive lesions. Piflufolastat is designed to enhance detection of metastases during PSMA-targeted PET.
Participants will receive a single injection of piflufolastat followed 1-2 hours later by a single whole-body PET-CT or PET-MRI scan. A study site at the Hoag Cancer Center in Irvine, California, welcomed the first of the trial’s 274 participants in February 2024. Sites in Tower Urology, Los Angeles, and the Cleveland Clinic, Ohio, are gearing up. Detection rate is the primary endpoint. Overall survival and QoL are not measured. More details at clinicaltrials.gov
Stages I-IV prostate cancer without bone metastases. People 60 years or older with this type of prostate cancer who are just starting androgen deprivation therapy are eligible for a phase 3, placebo-controlled trial investigating whether high-dose vitamin D can prevent or reduce androgen-deprivation therapy-induced bone loss.
For 1 year, participants will take tablets of high-dose vitamin D or a placebo and then undergo dual x-ray absorptiometry. The Ochsner Medical Center in Jefferson, Louisiana, started recruiting 366 trial participants in December 2023. Reduction in bone mineral density loss in the hip and spine over 1 year is the primary objective. QoL is a secondary objective, and overall survival will not be measured. More details at clinicaltrials.gov
Dr. Garnick expressed some concerns with the trial design so far, including that “the dose of vitamin D is not delineated nor is the target vitamin D level.”
All trial information is from the National Institutes of Health’s National Library of Medicine (online at clinicaltrials.gov). Dr. Garnick did not report conflicts with any of the trials.
A version of this article appeared on Medscape.com.
Metastatic castration-sensitive prostate cancer
Adults with this diagnosis may be interested in a randomized, double-blind, phase 3 study examining whether an experimental poly (ADP-ribose) polymerase (PARP) inhibitor called saruparib can further delay disease progression when added to a next-generation hormonal agent such as abiraterone (Zytiga), darolutamide (Nubeqa), or enzalutamide (Xtandi).
One group of participants will take daily oral doses of saruparib plus physician’s choice of a next-generation hormonal agent until disease progression or another reason for stopping therapy. The other group will add a placebo to a next-generation hormonal agent.
Sites in Rhode Island, Arkansas, California, Michigan, Australia, Canada, Japan, Taiwan, Thailand, the United Kingdom, and South Korea began seeking the trial’s 1800 participants in November 2023. Research centers in 31 other US states and 18 other countries are gearing up. The primary endpoint is radiographic progression-free survival. Overall survival and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov.
This news organization asked Marc Garnick, MD, professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, for his take on the trial. “The study is interesting since it is adding to the evaluations of continued intensification for first-line therapy and will help further elucidate the role of PARP inhibition regardless of homologous repair status,” Dr. Garnick said. “Plus, saruparib is supposedly more selective on PARP1, which in-and-of-itself is of potential benefit.”
Metastatic castration-resistant prostate cancer
People with this type of cancer who have progressed on a next-generation hormonal agent may be eligible for a randomized, open-label, phase 3 trial testing an investigational oral treatment called MK-5684 to see if it increases survival more effectively than switching to an alternative next-generation hormonal agent.
MK-5684 is designed to inhibit the CYP11A1 enzyme, thereby disrupting the androgen-receptor signaling pathway.
One group will take twice-daily tablets of MK-5684 plus hormone replacement therapy, oral dexamethasone, and oral fludrocortisone acetate (Florinef), with rescue hydrocortisone as needed. The other participants will take daily tablets of a next-generation hormonal agent: Either enzalutamide or abiraterone. Patients assigned to abiraterone will also be given prednisone tablets.
US-based sites in nine states and Puerto Rico started looking for the trial’s 1500 participants in December 2023 in partnership with study centers in Australia, Israel, South Korea, and Taiwan. The primary endpoints are radiographic progression-free survival and overall survival. QoL will not be tracked. More details at clinicaltrials.gov.
Metastatic castration-resistant prostate cancer
Patients in this situation who have progressed on taxane-based chemotherapy as well as a next-generation hormonal agent have the option to enroll in another phase 3 MK-5684 study.
Like the trial described above, all patients will remain on their respective therapy until disease progression. In this trial, one group will take twice-daily tablets of MK-5684 without hormone replacement therapy but the same mix of oral dexamethasone and fludrocortisone. Rescue hydrocortisone will also be available. The second group will be assigned either enzalutamide or abiraterone plus prednisone.
Sites in Puerto Rico, Colorado, Nevada, and Virginia, and five other countries outside the United States, opened their doors to the first of 1200 patients in December 2023. The primary endpoints are radiographic progression-free survival and overall survival, analyzed separately for patients with and without an androgen receptor ligand-binding domain mutation. QoL will not be measured. More details at clinicaltrials.gov.
High-risk prostate cancer
People with this diagnosis can join a randomized, open-label, phase 3 National Cancer Institute study to test whether stereotactic body radiation therapy (SBRT) is as effective as conventional external beam radiation therapy (EBRT) at preventing metastasis.
SBRT delivers radiation to tumors with higher precision than EBRT. The advantage of SBRT is the ability to deliver fewer doses over a shorter duration with less collateral damage to surrounding tissues.
In the trial, half of participants will undergo five treatments of SBRT over 2 weeks, while the other half will receive 20-45 treatments of EBRT over 4-9 weeks. Study sites in 14 US states began recruiting the trial’s 1209 participants in November 2023. Metastasis-free survival over 15 years is the primary endpoint, overall survival is a secondary endpoint, and QoL measures, apart from fatigue, will not be tracked. More details at clinicaltrials.gov.
Dr. Garnick viewed this study as “problematic because patient accrual ends in 2036 with a readout in 2041.” He added, “What its relevance will be at that time is unlikely to provide practice changes, since in that interval there will undoubtedly be multiple advances in place.”
Newly diagnosed favorable intermediate risk prostate cancer
People with this type of cancer are eligible for an open-label, phase 4 real-world study of a radioactive diagnostic agent called piflufolastat F 18 (Pylarify) that targets prostate-specific membrane antigen (PSMA)–positive lesions. Piflufolastat is designed to enhance detection of metastases during PSMA-targeted PET.
Participants will receive a single injection of piflufolastat followed 1-2 hours later by a single whole-body PET-CT or PET-MRI scan. A study site at the Hoag Cancer Center in Irvine, California, welcomed the first of the trial’s 274 participants in February 2024. Sites in Tower Urology, Los Angeles, and the Cleveland Clinic, Ohio, are gearing up. Detection rate is the primary endpoint. Overall survival and QoL are not measured. More details at clinicaltrials.gov
Stages I-IV prostate cancer without bone metastases. People 60 years or older with this type of prostate cancer who are just starting androgen deprivation therapy are eligible for a phase 3, placebo-controlled trial investigating whether high-dose vitamin D can prevent or reduce androgen-deprivation therapy-induced bone loss.
For 1 year, participants will take tablets of high-dose vitamin D or a placebo and then undergo dual x-ray absorptiometry. The Ochsner Medical Center in Jefferson, Louisiana, started recruiting 366 trial participants in December 2023. Reduction in bone mineral density loss in the hip and spine over 1 year is the primary objective. QoL is a secondary objective, and overall survival will not be measured. More details at clinicaltrials.gov
Dr. Garnick expressed some concerns with the trial design so far, including that “the dose of vitamin D is not delineated nor is the target vitamin D level.”
All trial information is from the National Institutes of Health’s National Library of Medicine (online at clinicaltrials.gov). Dr. Garnick did not report conflicts with any of the trials.
A version of this article appeared on Medscape.com.
Do Tumor-infiltrating Lymphocytes Predict Better Breast Cancer Outcomes?
The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.
Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.
“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”
What is Known About Tumor-Infiltrating Lymphocytes and Cancer?
Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.
Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.
The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview.
The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.
“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.
What Does the New Study Add?
The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.
The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.
A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.
Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.
The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.
“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.
What are the Limitations of This Research?
The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.
“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.
To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.
“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.
What Do Oncologists Need to Know?
The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.
“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”
In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.
Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.
What Additional Research is Needed?
Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.
“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.
The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.
The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.
Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.
“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”
What is Known About Tumor-Infiltrating Lymphocytes and Cancer?
Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.
Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.
The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview.
The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.
“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.
What Does the New Study Add?
The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.
The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.
A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.
Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.
The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.
“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.
What are the Limitations of This Research?
The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.
“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.
To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.
“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.
What Do Oncologists Need to Know?
The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.
“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”
In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.
Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.
What Additional Research is Needed?
Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.
“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.
The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.
The association of abundant tumor-infiltrating lymphocytes (TILs) in breast cancer tissue with outcomes in patients with early-stage triple-negative breast cancer (TNBC) who do not receive chemotherapy has not been well studied, wrote Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minnesota, and colleagues, in JAMA.
Biomarkers to guide systemic treatment and avoid overtreatment are lacking, and such markers could help identify patients who could achieve increased survival with less intensive therapy, continued the authors of the new study of nearly 2000 individuals.
“TNBC is the most aggressive subtype of breast cancer, and for this reason, current treatment guidelines recommend chemotherapy using multiple drugs either before or after surgery,” Dr. Leon-Ferre said in an interview. “We have learned over the last several years that TNBC is not a single disease, but that there are several subtypes of TNBC that have different risks and different vulnerabilities, and treating all patients similarly may not be optimal.”
What is Known About Tumor-Infiltrating Lymphocytes and Cancer?
Previous studies have shown improved survival in patients with early-stage TNBC and high levels of TILs who were treated with adjuvant and neoadjuvant chemotherapy, compared with those with lower TILs. In a pooled analysis of 2148 patients from nine studies published in the Journal of Clinical Oncology in 2019, a higher percentage of TILs in the stroma surrounding a tumor was significantly associated with improved survival in TNBC patients after adjuvant chemotherapy.
Another study published in the Journal of Clinical Oncology in 2022 showed that elevated TILs were significant predictors of overall survival, but the study included fewer than 500 patients.
The potential mechanisms that drive the association between elevated TILs and improved survival include the ability of TILs to attack cancer cells, Dr. Leon-Ferre said in an interview.
The goal of this study was to evaluate whether TILs could identify a subset of patients with TNBC who had a very low risk of cancer recurrence even if chemotherapy was not given.
“Indeed, we found that patients with stage I TNBC and high TILs had a very low risk of recurrence even when chemotherapy was not administered. These findings will pave the way for future studies aiming to reduce the need for multiple chemotherapy drugs in patients with stage I TNBC and decrease the side effects that patients face,” he said.
What Does the New Study Add?
The current study included 1966 individuals from 13 sites in North America, Europe, and Asia who were diagnosed with TNBC between 1979 and 2017 and were treated with surgery, with or without radiotherapy but with no adjuvant or neoadjuvant chemotherapy. The researchers examined the abundance of TILs in the breast tissue of resected primary tumors; the primary outcome was invasive disease-free survival (iDFS), with recurrence-free survival, distant recurrence-free survival, and overall survival as secondary outcomes.
The median age of the patients was 56 years, 55% had stage I TNBC, and the median TIL level was 15%.
A total of 417 patients had a TIL level of 50% or more, and the 5-year iDFS for these patients was 94%, compared with 78% for those with a TIL level less than 30%. Similarly, 5-year overall survival was 95% in patients with a TIL level of 50% or more, compared with 82% for patients with TIL levels of less than 30%.
Additionally, each 10% increase in TILs was independently associated not only with improved iDFS (hazard ratio[HR], 0.92), but also improved recurrence-free survival (HR, 0.90), distant recurrence-free survival (HR, 0.87), and overall survival (HR, 0.88) over a median follow-up of 18 years.
The current study shows that cancer stage based on tumor size and the number of lymph nodes should not be the only considerations for making treatment decisions and predicting outcomes, Dr. Leon-Ferre said in an interview.
“In fact, our study shows that for tumors of the same stage (particularly for stage I), the risk of recurrence is different depending on the number of TILs seen in the breast cancer tissue. When chemo is not given, those with high TILs have lower risk of recurrence, whereas those with low TILs have a higher risk of recurrence,” he said.
What are the Limitations of This Research?
The current study findings are limited by the retrospective design and use of observational data, so the researchers could not make conclusions about causality. Other limitations included lack of data on germline mutations and race or ethnicity, and the potential irrelevance of data from patients treated as long as 45 years ago.
“Because most patients with TNBC receive chemotherapy in the modern times, we needed to work with 13 hospitals around the world to find data on patients with TNBC who never received chemotherapy for various reasons,” Dr. Leon-Ferre said.
To address these limitations, Dr. Leone-Ferre and his colleagues are planning prospective studies where TILs will be used to make treatment decisions.
“Many of the patients in our cohort were treated many years ago, when chemotherapy was not routinely given. Advances in cancer detection, surgical and radiation techniques may lead to different results in patients treated today,” he added.
What Do Oncologists Need to Know?
The current study findings may provide additional information on prognosis that is important to share with patients for decision-making on the risks versus benefits of chemotherapy, Dr. Leon-Ferre said.
“Like any test, TILs should not be used in isolation to make decisions, but should be integrated with other factors including the cancer stage, the overall patient health, patient preferences, and concerns about treatment complications,” he emphasized. “The results of this study allow oncologists to offer a more refined calculation of recurrence risk if patients opt to not receive chemotherapy.”
In the current study, although younger age was associated with higher TIL levels, a finding consistent with previous studies, increased TIL, remained significantly associated with improved survival after adjusting for age, tumor size, nodal status, and histological grade.
Overall, “the findings suggest that for patients with stage I TNBC and TILs greater than 50%, chemotherapy may not be as necessary as it was previously thought,” Dr. Leon-Ferre said.
What Additional Research is Needed?
Prospective studies are needed to validate the findings, including studies in diverse populations, and additional studies may investigate whether early TBNC patients with high TIL levels could achieve high cure rates with less intensive and less toxic chemotherapy regiments than those currently recommended, the researchers wrote in their discussion.
“There are many additional research questions that we need to answer, and look forward to working on,” Dr. Leon-Ferre said, in an interview. These topics include whether TILs can be used to decide on the number of chemotherapy drugs a patient really needs and whether artificial intelligence can be used to evaluate TILs more quickly and effectively than the human eye, he said. Other research topics include identifying which particular type of TILs attack cancer cells most effectively and whether TILs could be increased in patients with low levels in order to improve their prognosis, he added.
The study was supported by the National Research Agency and General Secretariat for Investment, Clinical and Translational Science Awards, the Mayo Clinic Breast Cancer SPORE grant, the Cancer Research Society of Canada, institutional grants from the Dutch Cancer Society, The Netherlands Organization for Health Research, and several foundations. Dr. Leon-Ferre disclosed consulting honoraria to his institution for research activities from AstraZeneca, Gilead Sciences, and Lyell Immunopharma, with no personal fees outside the submitted work.
FROM JAMA
Virtual Reality Brings Relief to Hospitalized Patients With Cancer
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
FROM CANCER
Prostate Cancer Tsunami Coming, Experts Caution
An “inevitable” global surge in prostate cancer is coming, with a worldwide doubling of cases to 2.9 million and an 85% increase in deaths to nearly 700,000 by the year 2040, the Lancet Commission on Prostate Cancer warned this week.
At a meeting of urologists in Paris, the commission said that the acceleration is already underway in high-income countries such as the United States and the United Kingdom but will gain momentum in low- and medium-income countries.
Nick James, MD, lead author of The Lancet report and professor of prostate and bladder cancer research at The Institute of Cancer Research in London, said that the surge, in part, is a medical success story.
Dr. James told this news organization.
“There is a big rise in the high-income countries. But we’re going to see a big rise in the number of 50-, 60-, 70-year-olds in the coming decades in the poorer countries, and with that comes more prostate cancer. High-income countries such as the UK and USA will also see smaller increases for the same reason.”
According to the report, to be presented April 6 at the 2024 European Association of Urology Congress in Paris, “The case for prostate cancer screening for all men aged 50-70 years (and all men of African origin aged 45–70 years) in high-income countries is strengthening with improved use of technologies such as MRI and growing evidence for the safety of active surveillance.”
Andrew Vickers, PhD, a biostatistician at Memorial Sloan Kettering Cancer Center in New York City, said that the Lancet Commission came to similar conclusions as he and an international group of researchers did in a 2023 policy paper in The BMJ. A major gap, Dr. Vickers said, is misuse of prostate-specific antigen (PSA) screening.
“We found that the ubiquitous policy compromise of letting patients decide for themselves about PSA has led to the worst possible outcomes of overuse in men unlikely to benefit, high rates of overdiagnosis and overtreatment, and economic and racial inequity,” Dr. Vickers said. “Our view is that PSA screening should be done well — by implementing straightforward harm-reduction strategies like restricting screening in older men and use of secondary tests before biopsy — or not at all.”
Dr. James said that undertreatment of advanced disease is widespread; only about 30%-40% of men in the United States receive combination hormone therapy for metastatic disease, for example. “Simply doing what we know works would improve outcomes,” he said.
Dr. James said that men of African ancestry are twice as likely to develop prostate cancer, but whether treatment should follow a different approach in these men is unclear. The new report stressed the need to include more men of African ancestry in research.
Brandon Mahal, MD, vice chair of research in radiation oncology the University of Miami Sylvester Comprehensive Cancer Center and a coauthor of the report, said that new approaches are needed to enable earlier diagnosis of prostate cancer in men in low- to middle-income countries, where most patients present with metastatic disease and are less likely to survive for long periods.
Dr. James recommended pop-up clinics and mobile testing to encourage men who are at high risk for prostate cancer but feel well to detect lethal cancers early.
In England, for example, Dr. James helped introduce an outreach program called The Man Van which provided free health checks, including PSA tests, to high-risk men in London.
“By bringing a van with quick and easy testing straight to men at work and in the community, and targeting those who have a higher risk of prostate cancer, we provided thousands of health checks which resulted in almost 100 cancer diagnoses in men who might otherwise have only seen a doctor once their cancer has progressed to a more advanced stage,” he said.
He noted that the medical community worldwide is ill-prepared for the onslaught of prostate cancer cases.
“The solution cannot be training more urologists, radiation oncologists, pathologists, and radiologists because it simply takes too long,” Dr. James said. However, increased use of nurses and artificial intelligence may help. “In my own hospital, biopsies are a nurse-led and -delivered service. AI is extraordinarily good at diagnosis already and will only get better,” he said.
In poorer countries, smartphones could fill gaps too. “The same technology that does face recognition already can say that’s a Gleason 7 prostate cancer,” Dr. James said. “It’s not being rolled out in countries like America of course because pathologists’ income is at risk.”
Dr. James, Dr. Vickers, and Dr. Mahal reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
An “inevitable” global surge in prostate cancer is coming, with a worldwide doubling of cases to 2.9 million and an 85% increase in deaths to nearly 700,000 by the year 2040, the Lancet Commission on Prostate Cancer warned this week.
At a meeting of urologists in Paris, the commission said that the acceleration is already underway in high-income countries such as the United States and the United Kingdom but will gain momentum in low- and medium-income countries.
Nick James, MD, lead author of The Lancet report and professor of prostate and bladder cancer research at The Institute of Cancer Research in London, said that the surge, in part, is a medical success story.
Dr. James told this news organization.
“There is a big rise in the high-income countries. But we’re going to see a big rise in the number of 50-, 60-, 70-year-olds in the coming decades in the poorer countries, and with that comes more prostate cancer. High-income countries such as the UK and USA will also see smaller increases for the same reason.”
According to the report, to be presented April 6 at the 2024 European Association of Urology Congress in Paris, “The case for prostate cancer screening for all men aged 50-70 years (and all men of African origin aged 45–70 years) in high-income countries is strengthening with improved use of technologies such as MRI and growing evidence for the safety of active surveillance.”
Andrew Vickers, PhD, a biostatistician at Memorial Sloan Kettering Cancer Center in New York City, said that the Lancet Commission came to similar conclusions as he and an international group of researchers did in a 2023 policy paper in The BMJ. A major gap, Dr. Vickers said, is misuse of prostate-specific antigen (PSA) screening.
“We found that the ubiquitous policy compromise of letting patients decide for themselves about PSA has led to the worst possible outcomes of overuse in men unlikely to benefit, high rates of overdiagnosis and overtreatment, and economic and racial inequity,” Dr. Vickers said. “Our view is that PSA screening should be done well — by implementing straightforward harm-reduction strategies like restricting screening in older men and use of secondary tests before biopsy — or not at all.”
Dr. James said that undertreatment of advanced disease is widespread; only about 30%-40% of men in the United States receive combination hormone therapy for metastatic disease, for example. “Simply doing what we know works would improve outcomes,” he said.
Dr. James said that men of African ancestry are twice as likely to develop prostate cancer, but whether treatment should follow a different approach in these men is unclear. The new report stressed the need to include more men of African ancestry in research.
Brandon Mahal, MD, vice chair of research in radiation oncology the University of Miami Sylvester Comprehensive Cancer Center and a coauthor of the report, said that new approaches are needed to enable earlier diagnosis of prostate cancer in men in low- to middle-income countries, where most patients present with metastatic disease and are less likely to survive for long periods.
Dr. James recommended pop-up clinics and mobile testing to encourage men who are at high risk for prostate cancer but feel well to detect lethal cancers early.
In England, for example, Dr. James helped introduce an outreach program called The Man Van which provided free health checks, including PSA tests, to high-risk men in London.
“By bringing a van with quick and easy testing straight to men at work and in the community, and targeting those who have a higher risk of prostate cancer, we provided thousands of health checks which resulted in almost 100 cancer diagnoses in men who might otherwise have only seen a doctor once their cancer has progressed to a more advanced stage,” he said.
He noted that the medical community worldwide is ill-prepared for the onslaught of prostate cancer cases.
“The solution cannot be training more urologists, radiation oncologists, pathologists, and radiologists because it simply takes too long,” Dr. James said. However, increased use of nurses and artificial intelligence may help. “In my own hospital, biopsies are a nurse-led and -delivered service. AI is extraordinarily good at diagnosis already and will only get better,” he said.
In poorer countries, smartphones could fill gaps too. “The same technology that does face recognition already can say that’s a Gleason 7 prostate cancer,” Dr. James said. “It’s not being rolled out in countries like America of course because pathologists’ income is at risk.”
Dr. James, Dr. Vickers, and Dr. Mahal reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
An “inevitable” global surge in prostate cancer is coming, with a worldwide doubling of cases to 2.9 million and an 85% increase in deaths to nearly 700,000 by the year 2040, the Lancet Commission on Prostate Cancer warned this week.
At a meeting of urologists in Paris, the commission said that the acceleration is already underway in high-income countries such as the United States and the United Kingdom but will gain momentum in low- and medium-income countries.
Nick James, MD, lead author of The Lancet report and professor of prostate and bladder cancer research at The Institute of Cancer Research in London, said that the surge, in part, is a medical success story.
Dr. James told this news organization.
“There is a big rise in the high-income countries. But we’re going to see a big rise in the number of 50-, 60-, 70-year-olds in the coming decades in the poorer countries, and with that comes more prostate cancer. High-income countries such as the UK and USA will also see smaller increases for the same reason.”
According to the report, to be presented April 6 at the 2024 European Association of Urology Congress in Paris, “The case for prostate cancer screening for all men aged 50-70 years (and all men of African origin aged 45–70 years) in high-income countries is strengthening with improved use of technologies such as MRI and growing evidence for the safety of active surveillance.”
Andrew Vickers, PhD, a biostatistician at Memorial Sloan Kettering Cancer Center in New York City, said that the Lancet Commission came to similar conclusions as he and an international group of researchers did in a 2023 policy paper in The BMJ. A major gap, Dr. Vickers said, is misuse of prostate-specific antigen (PSA) screening.
“We found that the ubiquitous policy compromise of letting patients decide for themselves about PSA has led to the worst possible outcomes of overuse in men unlikely to benefit, high rates of overdiagnosis and overtreatment, and economic and racial inequity,” Dr. Vickers said. “Our view is that PSA screening should be done well — by implementing straightforward harm-reduction strategies like restricting screening in older men and use of secondary tests before biopsy — or not at all.”
Dr. James said that undertreatment of advanced disease is widespread; only about 30%-40% of men in the United States receive combination hormone therapy for metastatic disease, for example. “Simply doing what we know works would improve outcomes,” he said.
Dr. James said that men of African ancestry are twice as likely to develop prostate cancer, but whether treatment should follow a different approach in these men is unclear. The new report stressed the need to include more men of African ancestry in research.
Brandon Mahal, MD, vice chair of research in radiation oncology the University of Miami Sylvester Comprehensive Cancer Center and a coauthor of the report, said that new approaches are needed to enable earlier diagnosis of prostate cancer in men in low- to middle-income countries, where most patients present with metastatic disease and are less likely to survive for long periods.
Dr. James recommended pop-up clinics and mobile testing to encourage men who are at high risk for prostate cancer but feel well to detect lethal cancers early.
In England, for example, Dr. James helped introduce an outreach program called The Man Van which provided free health checks, including PSA tests, to high-risk men in London.
“By bringing a van with quick and easy testing straight to men at work and in the community, and targeting those who have a higher risk of prostate cancer, we provided thousands of health checks which resulted in almost 100 cancer diagnoses in men who might otherwise have only seen a doctor once their cancer has progressed to a more advanced stage,” he said.
He noted that the medical community worldwide is ill-prepared for the onslaught of prostate cancer cases.
“The solution cannot be training more urologists, radiation oncologists, pathologists, and radiologists because it simply takes too long,” Dr. James said. However, increased use of nurses and artificial intelligence may help. “In my own hospital, biopsies are a nurse-led and -delivered service. AI is extraordinarily good at diagnosis already and will only get better,” he said.
In poorer countries, smartphones could fill gaps too. “The same technology that does face recognition already can say that’s a Gleason 7 prostate cancer,” Dr. James said. “It’s not being rolled out in countries like America of course because pathologists’ income is at risk.”
Dr. James, Dr. Vickers, and Dr. Mahal reported no relevant financial conflicts of interest.
A version of this article appeared on Medscape.com.
Should Opioids Be Used for Chronic Cancer Pain?
from legal concerns to threats of violence, say the authors of new research.
These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.
“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
Who Should Manage Chronic Cancer Pain?
Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.
“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?
To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.
These interviews yielded three themes.
First, no “medical home” exists for chronic pain management in cancer survivors.
“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.
Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.
“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”
The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.
“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”
Meanwhile, a palliative care provider described legal pressure from the opposite direction:
“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”
Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?
After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.
They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.
Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.
This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.
from legal concerns to threats of violence, say the authors of new research.
These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.
“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
Who Should Manage Chronic Cancer Pain?
Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.
“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?
To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.
These interviews yielded three themes.
First, no “medical home” exists for chronic pain management in cancer survivors.
“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.
Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.
“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”
The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.
“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”
Meanwhile, a palliative care provider described legal pressure from the opposite direction:
“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”
Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?
After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.
They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.
Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.
This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.
from legal concerns to threats of violence, say the authors of new research.
These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.
“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
Who Should Manage Chronic Cancer Pain?
Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.
“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?
To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.
These interviews yielded three themes.
First, no “medical home” exists for chronic pain management in cancer survivors.
“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.
Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.
“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”
The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.
“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”
Meanwhile, a palliative care provider described legal pressure from the opposite direction:
“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”
Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?
After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.
They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.
Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.
This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.
FROM CANCER
Certain Pesticides Linked With Risk for Pancreatic Cancer
One of them, a case-control study, showed an elevated risk in individuals whose adipose tissue contained substances that are now banned.
“The association between pesticides and pancreatic cancer exists. It is of low magnitude but robust, concerning cumulative pesticides and three substances: Mancozeb, glyphosate, and sulfur in spray form,” said Mathias Brugel, MD, hospital practitioner at Basque Coast Hospital Center in Bayonne, France, during his presentation.
Regarding the four other liposoluble substances associated with an increased risk for pancreatic cancer in the second study, “their use has been banned since the 1990s, but they are still present in soils and in the air,” Dr. Brugel told this news organization.
For example, in Reims, France, the assessment of air quality by ATMO Grand Est revealed the presence of banned pesticides in the air, he added. However, Dr. Brugel stressed that a cause-effect relationship between pesticide exposure and the risk for pancreatic cancer cannot be established with these studies.
Incidence Rising Constantly
The incidence of pancreatic adenocarcinoma has been increasing steadily for more than 30 years. In France, nearly 16,000 new cases were reported in 2023, which represented an annual increase of about 2%. According to the National Cancer Institute, “pancreatic adenocarcinoma could become the second leading cause of cancer mortality by 2030.”
“This increase in incidence is particularly strong in France compared with other Western countries. The causes are still poorly understood. One might wonder whether environmental factors like pesticides are involved,” said Dr. Brugel.
Known to have a mechanism of action favoring oncogenesis, pesticides are suspected of being responsible for the rise in certain cancers, especially given their extensive use in France. In total, around 300 substances are authorized, and 65,000 tons are applied each year, making France the largest consumer of pesticides in Europe.
“Contamination is ubiquitous, meaning they are found in soil, water, air, and in individuals,” said Dr. Brugel. According to a study by the Institute for Scientific Expertise Research, pesticide residues were detected in 64% of hair samples taken from French volunteers.
The literature increasingly reported data suggesting a link between pesticide exposure and the development of certain diseases like cancer. A 2021 document by Inserm notably confirmed the strong presumption of a link between occupational pesticide exposure and pathologies such as non-Hodgkin’s lymphoma and prostate cancer.
High-Incidence Zones
To explore the link between pesticide exposure and pancreatic cancer, Dr. Brugel and his colleagues conducted the EcoPESTIPAC and PESTIPAC studies, the results of which were presented at this year’s conference.
In EcoPESTIPAC, researchers conducted a national ecological regression by dividing the entire French territory into 5529 spatial units. The number of pancreatic cancer cases per spatial unit per year (disease-mapping) was determined using the National Health Data System.
Nine chemicals, including glyphosate, were included, thus covering half of pesticide purchases in France. The cumulative quantity of pesticides, regardless of molecule, was also examined. Pesticide exposure was estimated by the median ratio between pesticide purchase and agricultural area per spatial unit over an 11-year period from early 2011 to the end of 2021.
Mor than 134,000 cases of pancreatic cancer were reported during this period. The analysis revealed three high-incidence zones located around Paris, in central France, and in the Mediterranean basin, while spatial units in the western region showed the lowest incidences.
The heterogeneous distribution of the disease suggests the involvement of risk factors, said Dr. Brugel. After adjusting for confounding factors such as smoking, the study showed an increased risk for pancreatic cancer associated with the cumulative quantity of pesticides and three specific substances: Sulfur in spray form, mancozeb, and glyphosate.
Risk Increases
A dose-response relationship was evident. For an increase in pesticide use of 2.5 kg/hectare over 11 years, the risk for pancreatic adenocarcinoma increased from 0.9% to 1.4%. “The increase is relatively small, but one must not forget that this risk applies to all of France,” said Dr. Brugel. Indeed, the risk appeared homogeneous across the entire territory.
This was the first study to explore this link at the national level. Although the association between the four identified factors and pancreatic risk was robust, the study had some limitations. It relied on the quantities of pesticides purchased to estimate the quantities used, Dr. Brugel pointed out.
The second study, PESTIPAC, was a case-control study conducted at the Reims University Hospital to explore the association between pancreatic adenocarcinoma and concentrations of organochlorine pesticides in fat and urine.
The study included 26 patients with pancreatic cancer who had abdominal surgery that allowed for adipose tissue sampling (minimum 10 g). Urine was collected in the morning on an empty stomach.
A control group was formed by including 26 other patients who underwent surgery for a benign abdominal condition such as gallstones or hernia, thus allowing for the same sampling. Individuals in both groups were matched for age and body mass index, two risk factors for pancreatic cancer.
Banned Substances
In total, 345 substances were searched for using chromatography and mass spectrometry. Analyses revealed the presence of five banned substances in all patients, while nine substances were found in half of the samples.
“Contamination is very widespread, both in patients with pancreatic cancer and in the controls,” said Dr. Brugel. Consequently, for this study, between-group comparisons of substances present in all individuals could not be performed.
After adjustment, an association with an increased risk for pancreatic cancer was nonetheless observed with four liposoluble substances: 4,4-DDE, mirex or perchlordecone, trans-nonachlor, and cis-nonachlor. All four substances are herbicides that have been banned for at least 30 years.
The study also aimed to assess the effect of pesticide presence in the body on survival after pancreatic cancer. The results showed no significant difference for overall survival or progression-free survival.
“Pesticides are a credible candidate to explain the increase in the incidence of pancreatic adenocarcinoma,” said Dr. Brugel. However, “if associations between pancreatic cancer and pesticides exist, they remain poorly understood, and it is difficult to establish clear causality.”
Further large-scale studies will be needed to confirm these associations. An evaluation of the general population’s exposure to banned substances also appears justified, according to the researchers.
This story was translated from the Medscape French edition 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.
One of them, a case-control study, showed an elevated risk in individuals whose adipose tissue contained substances that are now banned.
“The association between pesticides and pancreatic cancer exists. It is of low magnitude but robust, concerning cumulative pesticides and three substances: Mancozeb, glyphosate, and sulfur in spray form,” said Mathias Brugel, MD, hospital practitioner at Basque Coast Hospital Center in Bayonne, France, during his presentation.
Regarding the four other liposoluble substances associated with an increased risk for pancreatic cancer in the second study, “their use has been banned since the 1990s, but they are still present in soils and in the air,” Dr. Brugel told this news organization.
For example, in Reims, France, the assessment of air quality by ATMO Grand Est revealed the presence of banned pesticides in the air, he added. However, Dr. Brugel stressed that a cause-effect relationship between pesticide exposure and the risk for pancreatic cancer cannot be established with these studies.
Incidence Rising Constantly
The incidence of pancreatic adenocarcinoma has been increasing steadily for more than 30 years. In France, nearly 16,000 new cases were reported in 2023, which represented an annual increase of about 2%. According to the National Cancer Institute, “pancreatic adenocarcinoma could become the second leading cause of cancer mortality by 2030.”
“This increase in incidence is particularly strong in France compared with other Western countries. The causes are still poorly understood. One might wonder whether environmental factors like pesticides are involved,” said Dr. Brugel.
Known to have a mechanism of action favoring oncogenesis, pesticides are suspected of being responsible for the rise in certain cancers, especially given their extensive use in France. In total, around 300 substances are authorized, and 65,000 tons are applied each year, making France the largest consumer of pesticides in Europe.
“Contamination is ubiquitous, meaning they are found in soil, water, air, and in individuals,” said Dr. Brugel. According to a study by the Institute for Scientific Expertise Research, pesticide residues were detected in 64% of hair samples taken from French volunteers.
The literature increasingly reported data suggesting a link between pesticide exposure and the development of certain diseases like cancer. A 2021 document by Inserm notably confirmed the strong presumption of a link between occupational pesticide exposure and pathologies such as non-Hodgkin’s lymphoma and prostate cancer.
High-Incidence Zones
To explore the link between pesticide exposure and pancreatic cancer, Dr. Brugel and his colleagues conducted the EcoPESTIPAC and PESTIPAC studies, the results of which were presented at this year’s conference.
In EcoPESTIPAC, researchers conducted a national ecological regression by dividing the entire French territory into 5529 spatial units. The number of pancreatic cancer cases per spatial unit per year (disease-mapping) was determined using the National Health Data System.
Nine chemicals, including glyphosate, were included, thus covering half of pesticide purchases in France. The cumulative quantity of pesticides, regardless of molecule, was also examined. Pesticide exposure was estimated by the median ratio between pesticide purchase and agricultural area per spatial unit over an 11-year period from early 2011 to the end of 2021.
Mor than 134,000 cases of pancreatic cancer were reported during this period. The analysis revealed three high-incidence zones located around Paris, in central France, and in the Mediterranean basin, while spatial units in the western region showed the lowest incidences.
The heterogeneous distribution of the disease suggests the involvement of risk factors, said Dr. Brugel. After adjusting for confounding factors such as smoking, the study showed an increased risk for pancreatic cancer associated with the cumulative quantity of pesticides and three specific substances: Sulfur in spray form, mancozeb, and glyphosate.
Risk Increases
A dose-response relationship was evident. For an increase in pesticide use of 2.5 kg/hectare over 11 years, the risk for pancreatic adenocarcinoma increased from 0.9% to 1.4%. “The increase is relatively small, but one must not forget that this risk applies to all of France,” said Dr. Brugel. Indeed, the risk appeared homogeneous across the entire territory.
This was the first study to explore this link at the national level. Although the association between the four identified factors and pancreatic risk was robust, the study had some limitations. It relied on the quantities of pesticides purchased to estimate the quantities used, Dr. Brugel pointed out.
The second study, PESTIPAC, was a case-control study conducted at the Reims University Hospital to explore the association between pancreatic adenocarcinoma and concentrations of organochlorine pesticides in fat and urine.
The study included 26 patients with pancreatic cancer who had abdominal surgery that allowed for adipose tissue sampling (minimum 10 g). Urine was collected in the morning on an empty stomach.
A control group was formed by including 26 other patients who underwent surgery for a benign abdominal condition such as gallstones or hernia, thus allowing for the same sampling. Individuals in both groups were matched for age and body mass index, two risk factors for pancreatic cancer.
Banned Substances
In total, 345 substances were searched for using chromatography and mass spectrometry. Analyses revealed the presence of five banned substances in all patients, while nine substances were found in half of the samples.
“Contamination is very widespread, both in patients with pancreatic cancer and in the controls,” said Dr. Brugel. Consequently, for this study, between-group comparisons of substances present in all individuals could not be performed.
After adjustment, an association with an increased risk for pancreatic cancer was nonetheless observed with four liposoluble substances: 4,4-DDE, mirex or perchlordecone, trans-nonachlor, and cis-nonachlor. All four substances are herbicides that have been banned for at least 30 years.
The study also aimed to assess the effect of pesticide presence in the body on survival after pancreatic cancer. The results showed no significant difference for overall survival or progression-free survival.
“Pesticides are a credible candidate to explain the increase in the incidence of pancreatic adenocarcinoma,” said Dr. Brugel. However, “if associations between pancreatic cancer and pesticides exist, they remain poorly understood, and it is difficult to establish clear causality.”
Further large-scale studies will be needed to confirm these associations. An evaluation of the general population’s exposure to banned substances also appears justified, according to the researchers.
This story was translated from the Medscape French edition 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.
One of them, a case-control study, showed an elevated risk in individuals whose adipose tissue contained substances that are now banned.
“The association between pesticides and pancreatic cancer exists. It is of low magnitude but robust, concerning cumulative pesticides and three substances: Mancozeb, glyphosate, and sulfur in spray form,” said Mathias Brugel, MD, hospital practitioner at Basque Coast Hospital Center in Bayonne, France, during his presentation.
Regarding the four other liposoluble substances associated with an increased risk for pancreatic cancer in the second study, “their use has been banned since the 1990s, but they are still present in soils and in the air,” Dr. Brugel told this news organization.
For example, in Reims, France, the assessment of air quality by ATMO Grand Est revealed the presence of banned pesticides in the air, he added. However, Dr. Brugel stressed that a cause-effect relationship between pesticide exposure and the risk for pancreatic cancer cannot be established with these studies.
Incidence Rising Constantly
The incidence of pancreatic adenocarcinoma has been increasing steadily for more than 30 years. In France, nearly 16,000 new cases were reported in 2023, which represented an annual increase of about 2%. According to the National Cancer Institute, “pancreatic adenocarcinoma could become the second leading cause of cancer mortality by 2030.”
“This increase in incidence is particularly strong in France compared with other Western countries. The causes are still poorly understood. One might wonder whether environmental factors like pesticides are involved,” said Dr. Brugel.
Known to have a mechanism of action favoring oncogenesis, pesticides are suspected of being responsible for the rise in certain cancers, especially given their extensive use in France. In total, around 300 substances are authorized, and 65,000 tons are applied each year, making France the largest consumer of pesticides in Europe.
“Contamination is ubiquitous, meaning they are found in soil, water, air, and in individuals,” said Dr. Brugel. According to a study by the Institute for Scientific Expertise Research, pesticide residues were detected in 64% of hair samples taken from French volunteers.
The literature increasingly reported data suggesting a link between pesticide exposure and the development of certain diseases like cancer. A 2021 document by Inserm notably confirmed the strong presumption of a link between occupational pesticide exposure and pathologies such as non-Hodgkin’s lymphoma and prostate cancer.
High-Incidence Zones
To explore the link between pesticide exposure and pancreatic cancer, Dr. Brugel and his colleagues conducted the EcoPESTIPAC and PESTIPAC studies, the results of which were presented at this year’s conference.
In EcoPESTIPAC, researchers conducted a national ecological regression by dividing the entire French territory into 5529 spatial units. The number of pancreatic cancer cases per spatial unit per year (disease-mapping) was determined using the National Health Data System.
Nine chemicals, including glyphosate, were included, thus covering half of pesticide purchases in France. The cumulative quantity of pesticides, regardless of molecule, was also examined. Pesticide exposure was estimated by the median ratio between pesticide purchase and agricultural area per spatial unit over an 11-year period from early 2011 to the end of 2021.
Mor than 134,000 cases of pancreatic cancer were reported during this period. The analysis revealed three high-incidence zones located around Paris, in central France, and in the Mediterranean basin, while spatial units in the western region showed the lowest incidences.
The heterogeneous distribution of the disease suggests the involvement of risk factors, said Dr. Brugel. After adjusting for confounding factors such as smoking, the study showed an increased risk for pancreatic cancer associated with the cumulative quantity of pesticides and three specific substances: Sulfur in spray form, mancozeb, and glyphosate.
Risk Increases
A dose-response relationship was evident. For an increase in pesticide use of 2.5 kg/hectare over 11 years, the risk for pancreatic adenocarcinoma increased from 0.9% to 1.4%. “The increase is relatively small, but one must not forget that this risk applies to all of France,” said Dr. Brugel. Indeed, the risk appeared homogeneous across the entire territory.
This was the first study to explore this link at the national level. Although the association between the four identified factors and pancreatic risk was robust, the study had some limitations. It relied on the quantities of pesticides purchased to estimate the quantities used, Dr. Brugel pointed out.
The second study, PESTIPAC, was a case-control study conducted at the Reims University Hospital to explore the association between pancreatic adenocarcinoma and concentrations of organochlorine pesticides in fat and urine.
The study included 26 patients with pancreatic cancer who had abdominal surgery that allowed for adipose tissue sampling (minimum 10 g). Urine was collected in the morning on an empty stomach.
A control group was formed by including 26 other patients who underwent surgery for a benign abdominal condition such as gallstones or hernia, thus allowing for the same sampling. Individuals in both groups were matched for age and body mass index, two risk factors for pancreatic cancer.
Banned Substances
In total, 345 substances were searched for using chromatography and mass spectrometry. Analyses revealed the presence of five banned substances in all patients, while nine substances were found in half of the samples.
“Contamination is very widespread, both in patients with pancreatic cancer and in the controls,” said Dr. Brugel. Consequently, for this study, between-group comparisons of substances present in all individuals could not be performed.
After adjustment, an association with an increased risk for pancreatic cancer was nonetheless observed with four liposoluble substances: 4,4-DDE, mirex or perchlordecone, trans-nonachlor, and cis-nonachlor. All four substances are herbicides that have been banned for at least 30 years.
The study also aimed to assess the effect of pesticide presence in the body on survival after pancreatic cancer. The results showed no significant difference for overall survival or progression-free survival.
“Pesticides are a credible candidate to explain the increase in the incidence of pancreatic adenocarcinoma,” said Dr. Brugel. However, “if associations between pancreatic cancer and pesticides exist, they remain poorly understood, and it is difficult to establish clear causality.”
Further large-scale studies will be needed to confirm these associations. An evaluation of the general population’s exposure to banned substances also appears justified, according to the researchers.
This story was translated from the Medscape French edition 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.
Polygenic Risk Scores Improve Breast Cancer Screening
TOPLINE:
METHODOLOGY:
A polygenic risk score — a measure of an individual’s risk for a disease based on the estimated effects of many genetic variants — is not typically included alongside family histories and pathogenic variants of genes, such as BRCA1 and PALB2, when assessing a woman’s risk for breast cancer and the need for earlier or more frequent screening.
To assess the potential for a polygenic risk score to improve breast cancer risk stratification, investigators in Finland used a nationwide genetic database to calculate polygenic risk score scores for 117,252 women and then linked the scores to their breast cancer outcomes, using the country’s nationwide mammography screening program, which screens women, ages 50-69 years, every 2 years.
The researchers evaluated the use of polygenic risk scores both alone and in combination with family histories and pathogenic variants — specifically, CHEK2 and PALB2 variants common in Finland.
The researchers also looked at how well polygenic risk scores predicted a person’s risk for any breast cancer as well as invasive, in situ, and bilateral at three timepoints: before, during, and after screening age.
TAKEAWAY:
Compared with a lower polygenic risk score (below 90%), a high polygenic risk score — a score in the top 10% — was associated with more than a twofold higher risk for any breast cancer before, during, and after screening age (hazard ratio [HR], 2.50, 2.38, and 2.11, respectively). Pathogenic variants and family histories led to similar risk assessments (HR, 3.13, 2.30, and 1.95, respectively, for pathogenic variants; HR, 1.97, 1.96, and 1.68, respectively, for family history).
A high polygenic risk score had a positive predictive value of 39.5% for a breast cancer diagnosis after a positive screening mammography, about the same as positive family history (35.5%) and pathogenic variants (35.9%). Combining a high polygenic risk score with a positive family history increased the positive predictive value to 44.6% and with pathogenic variant carriers increased the positive predictive value to 50.6%.
A high polygenic risk score was also associated with a twofold higher risk for interval breast cancer — a cancer diagnosed between screenings — and a higher risk for bilateral breast cancer during screening ages (HR, 4.71), suggesting that women with high scores may benefit from a shorter time interval between screenings or earlier screening, the researchers said.
Women with scores in the bottom 10% had a very low risk for both interval and screen-detected cancers. Those with negative family histories and no pathogenic variants did not reach the 2% cumulative incidence threshold for breast cancer screening until age 62 years, “suggesting opportunities for less frequent screens,” the researchers noted.
IN PRACTICE:
This study demonstrates the effectiveness of using a breast cancer polygenic risk score for risk stratification, “with optimal stratification reached through combining” this information with family history and pathogenic variants, the researchers concluded.
SOURCE:
The study, led by Nina Mars, MD, PhD, of the University of Helsinki, Helsinki, Finland, was published in the Journal of Clinical Oncology.
LIMITATIONS:
The work was limited largely to people with Finnish genetic ancestry. The benefits of including polygenic risk scores in screening programs need to be confirmed in clinical trials in areas with broader genetic ancestry; several trials are underway in the United States and elsewhere.
DISCLOSURES:
The study was funded by the European Union’s Horizon 2020 research and innovation program, the Cancer Foundation Finland, and others. The investigators didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
A polygenic risk score — a measure of an individual’s risk for a disease based on the estimated effects of many genetic variants — is not typically included alongside family histories and pathogenic variants of genes, such as BRCA1 and PALB2, when assessing a woman’s risk for breast cancer and the need for earlier or more frequent screening.
To assess the potential for a polygenic risk score to improve breast cancer risk stratification, investigators in Finland used a nationwide genetic database to calculate polygenic risk score scores for 117,252 women and then linked the scores to their breast cancer outcomes, using the country’s nationwide mammography screening program, which screens women, ages 50-69 years, every 2 years.
The researchers evaluated the use of polygenic risk scores both alone and in combination with family histories and pathogenic variants — specifically, CHEK2 and PALB2 variants common in Finland.
The researchers also looked at how well polygenic risk scores predicted a person’s risk for any breast cancer as well as invasive, in situ, and bilateral at three timepoints: before, during, and after screening age.
TAKEAWAY:
Compared with a lower polygenic risk score (below 90%), a high polygenic risk score — a score in the top 10% — was associated with more than a twofold higher risk for any breast cancer before, during, and after screening age (hazard ratio [HR], 2.50, 2.38, and 2.11, respectively). Pathogenic variants and family histories led to similar risk assessments (HR, 3.13, 2.30, and 1.95, respectively, for pathogenic variants; HR, 1.97, 1.96, and 1.68, respectively, for family history).
A high polygenic risk score had a positive predictive value of 39.5% for a breast cancer diagnosis after a positive screening mammography, about the same as positive family history (35.5%) and pathogenic variants (35.9%). Combining a high polygenic risk score with a positive family history increased the positive predictive value to 44.6% and with pathogenic variant carriers increased the positive predictive value to 50.6%.
A high polygenic risk score was also associated with a twofold higher risk for interval breast cancer — a cancer diagnosed between screenings — and a higher risk for bilateral breast cancer during screening ages (HR, 4.71), suggesting that women with high scores may benefit from a shorter time interval between screenings or earlier screening, the researchers said.
Women with scores in the bottom 10% had a very low risk for both interval and screen-detected cancers. Those with negative family histories and no pathogenic variants did not reach the 2% cumulative incidence threshold for breast cancer screening until age 62 years, “suggesting opportunities for less frequent screens,” the researchers noted.
IN PRACTICE:
This study demonstrates the effectiveness of using a breast cancer polygenic risk score for risk stratification, “with optimal stratification reached through combining” this information with family history and pathogenic variants, the researchers concluded.
SOURCE:
The study, led by Nina Mars, MD, PhD, of the University of Helsinki, Helsinki, Finland, was published in the Journal of Clinical Oncology.
LIMITATIONS:
The work was limited largely to people with Finnish genetic ancestry. The benefits of including polygenic risk scores in screening programs need to be confirmed in clinical trials in areas with broader genetic ancestry; several trials are underway in the United States and elsewhere.
DISCLOSURES:
The study was funded by the European Union’s Horizon 2020 research and innovation program, the Cancer Foundation Finland, and others. The investigators didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
A polygenic risk score — a measure of an individual’s risk for a disease based on the estimated effects of many genetic variants — is not typically included alongside family histories and pathogenic variants of genes, such as BRCA1 and PALB2, when assessing a woman’s risk for breast cancer and the need for earlier or more frequent screening.
To assess the potential for a polygenic risk score to improve breast cancer risk stratification, investigators in Finland used a nationwide genetic database to calculate polygenic risk score scores for 117,252 women and then linked the scores to their breast cancer outcomes, using the country’s nationwide mammography screening program, which screens women, ages 50-69 years, every 2 years.
The researchers evaluated the use of polygenic risk scores both alone and in combination with family histories and pathogenic variants — specifically, CHEK2 and PALB2 variants common in Finland.
The researchers also looked at how well polygenic risk scores predicted a person’s risk for any breast cancer as well as invasive, in situ, and bilateral at three timepoints: before, during, and after screening age.
TAKEAWAY:
Compared with a lower polygenic risk score (below 90%), a high polygenic risk score — a score in the top 10% — was associated with more than a twofold higher risk for any breast cancer before, during, and after screening age (hazard ratio [HR], 2.50, 2.38, and 2.11, respectively). Pathogenic variants and family histories led to similar risk assessments (HR, 3.13, 2.30, and 1.95, respectively, for pathogenic variants; HR, 1.97, 1.96, and 1.68, respectively, for family history).
A high polygenic risk score had a positive predictive value of 39.5% for a breast cancer diagnosis after a positive screening mammography, about the same as positive family history (35.5%) and pathogenic variants (35.9%). Combining a high polygenic risk score with a positive family history increased the positive predictive value to 44.6% and with pathogenic variant carriers increased the positive predictive value to 50.6%.
A high polygenic risk score was also associated with a twofold higher risk for interval breast cancer — a cancer diagnosed between screenings — and a higher risk for bilateral breast cancer during screening ages (HR, 4.71), suggesting that women with high scores may benefit from a shorter time interval between screenings or earlier screening, the researchers said.
Women with scores in the bottom 10% had a very low risk for both interval and screen-detected cancers. Those with negative family histories and no pathogenic variants did not reach the 2% cumulative incidence threshold for breast cancer screening until age 62 years, “suggesting opportunities for less frequent screens,” the researchers noted.
IN PRACTICE:
This study demonstrates the effectiveness of using a breast cancer polygenic risk score for risk stratification, “with optimal stratification reached through combining” this information with family history and pathogenic variants, the researchers concluded.
SOURCE:
The study, led by Nina Mars, MD, PhD, of the University of Helsinki, Helsinki, Finland, was published in the Journal of Clinical Oncology.
LIMITATIONS:
The work was limited largely to people with Finnish genetic ancestry. The benefits of including polygenic risk scores in screening programs need to be confirmed in clinical trials in areas with broader genetic ancestry; several trials are underway in the United States and elsewhere.
DISCLOSURES:
The study was funded by the European Union’s Horizon 2020 research and innovation program, the Cancer Foundation Finland, and others. The investigators didn’t have any relevant disclosures.
A version of this article appeared on Medscape.com.
A Banned Chemical That Is Still Causing Cancer
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.