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FDA Approves Bizengri for NSCLC and Pancreatic Cancers Harboring NRG1 Gene Fusion
Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.
The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.
Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.
“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
The agent is expected to be available for use in the “coming weeks,” according to Merus.
“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”
Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.
Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.
The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.
Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.
“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
The agent is expected to be available for use in the “coming weeks,” according to Merus.
“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”
Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.
Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.
The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.
Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.
“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
The agent is expected to be available for use in the “coming weeks,” according to Merus.
“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”
Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.
Identifying the Best Upfront Regimen for Unresectable CRC Liver Metastasis
A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.
The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.
In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).
The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.
The analysis did not stop there in defining the optimal upfront therapy for this patient population.
In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.
Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.
In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.
Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.
Why Does This Clarity Matter?
The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.
In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.
As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.
Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.
Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.
Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.
The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.
Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.
Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).
ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.
CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.
A version of this article first appeared on Medscape.com.
A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.
The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.
In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).
The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.
The analysis did not stop there in defining the optimal upfront therapy for this patient population.
In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.
Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.
In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.
Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.
Why Does This Clarity Matter?
The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.
In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.
As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.
Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.
Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.
Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.
The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.
Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.
Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).
ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.
CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.
A version of this article first appeared on Medscape.com.
A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.
The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.
In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).
The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.
The analysis did not stop there in defining the optimal upfront therapy for this patient population.
In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.
Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.
In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.
Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.
Why Does This Clarity Matter?
The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.
In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.
As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.
Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.
Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.
Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.
The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.
Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.
Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).
ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.
CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
Are Endocrine Disruptors Really a Threat to Health?
Endocrine disruptors (EDs) — chemicals in the environment that could affect human endocrine function — are increasingly becoming a prominent concern for the public as well as professionals. At its 40th congress, the French Society of Endocrinology hosted a public lecture on the subject, given by Nicolas Chevalier, MD, PhD, professor of endocrinology at the University Hospital of Nice in France.
Environmental EDs
Chevalier began by asking the audience to remember one number: 906. This is the number of substances identified by the French Agency for Food, Environmental and Occupational Health & Safety for which there are sufficient scientific data to confirm or at least suspect endocrine-disrupting activity. In reality, the number is likely closer to 10,000, he said.
These chemicals include bisphenol A and its substitutes, parabens, phthalates, and pesticides. Additionally, lithium (mainly found in batteries), polychlorinated biphenyls, per- and polyfluoroalkyl substances, and polybromodiphenyl ethers, or brominated flame retardants, are included. These products are found throughout our environment, so much so that Chevalier said: “We are swimming in a soup of endocrine disruptors.”
The main source of human contamination is food, responsible for an estimated 80%-90% of those encountered. They may enter the food supply during production or preservation, and pesticides are not the only culprits. For example, fatty fish contain heavy metals. Water is also a significant source of contamination. It is worth noting that tap water is the cleanest and most monitored type when it comes to EDs. However, plastic bottles leach not only EDs but also microplastics, which are a major environmental pollution source.
Many other features in our daily environment contain EDs: Clothing (especially shoes), nonstick cookware, plastic containers (especially those heated in the microwave), plastic toys (which young children often put in their mouths), and cosmetic products (makeup, which is increasingly used by young girls). The placenta is not the barrier it was once thought to be: Amniotic fluid has been found to contain about 35 molecules that are toxic for the fetus, with at least 11 or 12 exceeding safety thresholds.
Multiple Linked Diseases
An incomplete list of ED-related diseases would include cancer, infertility, obesity, and diabetes, Chevalier said. Are these data alarmist? he asked. After all, life expectancy has increased globally by more than 10 years since the 1970s, and this has occurred alongside the increased use of EDs. However, he suggested remembering a second number: 157. This represents the billions of euros in European healthcare costs primarily caused by neurologic disorders linked to pesticides. They have a half-life estimated at least 10 years, and banning them will not stop them from persisting in the environment for up to 40 years. US studies have shown that their presence in the environment contributes to cognitive delays in young children.
Another area of concern is the rising infertility rates among couples, now affecting around one in five in France. This trend has been linked to the toxicity of EDs on the genital tract, especially in men, and is not only related to increased use of birth control. For example, in sub-Saharan Africa, rates of contraceptive use have increased only marginally, but birth rates have significantly decreased in areas contaminated by waste that is inadequately managed by Western standards.
EDs have also been implicated in the rising incidence of several cancers, including breast cancer in women and prostate cancer in men, and may have contributed to increases in both childhood obesity and adult diabetes.
A Difficult Battle
Chevalier asked: Is the increase in ED contamination inevitable? No, he said, but it is extremely difficult to counter. Governments are reluctant to legislate, particularly when jobs are at stake, even though certain workers are particularly exposed. The ideal situation would be for the public to take matters into their own hands by eliminating EDs from their environment through daily actions that pressure policymakers to act. For example:
- Eliminate plastics (especially for food products) and nonstick coatings
- Reject most cleaning products in favor of traditional solutions (eg, white vinegar and baking soda)
- Avoid imported toys (as producer countries often fail to comply with European health standards)
Environmental charters have been created by several local authorities and regional health agencies. Chevalier urged the public to rely on their recommendations and resources to help drive change.
This story was translated from Univadis France 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.
Endocrine disruptors (EDs) — chemicals in the environment that could affect human endocrine function — are increasingly becoming a prominent concern for the public as well as professionals. At its 40th congress, the French Society of Endocrinology hosted a public lecture on the subject, given by Nicolas Chevalier, MD, PhD, professor of endocrinology at the University Hospital of Nice in France.
Environmental EDs
Chevalier began by asking the audience to remember one number: 906. This is the number of substances identified by the French Agency for Food, Environmental and Occupational Health & Safety for which there are sufficient scientific data to confirm or at least suspect endocrine-disrupting activity. In reality, the number is likely closer to 10,000, he said.
These chemicals include bisphenol A and its substitutes, parabens, phthalates, and pesticides. Additionally, lithium (mainly found in batteries), polychlorinated biphenyls, per- and polyfluoroalkyl substances, and polybromodiphenyl ethers, or brominated flame retardants, are included. These products are found throughout our environment, so much so that Chevalier said: “We are swimming in a soup of endocrine disruptors.”
The main source of human contamination is food, responsible for an estimated 80%-90% of those encountered. They may enter the food supply during production or preservation, and pesticides are not the only culprits. For example, fatty fish contain heavy metals. Water is also a significant source of contamination. It is worth noting that tap water is the cleanest and most monitored type when it comes to EDs. However, plastic bottles leach not only EDs but also microplastics, which are a major environmental pollution source.
Many other features in our daily environment contain EDs: Clothing (especially shoes), nonstick cookware, plastic containers (especially those heated in the microwave), plastic toys (which young children often put in their mouths), and cosmetic products (makeup, which is increasingly used by young girls). The placenta is not the barrier it was once thought to be: Amniotic fluid has been found to contain about 35 molecules that are toxic for the fetus, with at least 11 or 12 exceeding safety thresholds.
Multiple Linked Diseases
An incomplete list of ED-related diseases would include cancer, infertility, obesity, and diabetes, Chevalier said. Are these data alarmist? he asked. After all, life expectancy has increased globally by more than 10 years since the 1970s, and this has occurred alongside the increased use of EDs. However, he suggested remembering a second number: 157. This represents the billions of euros in European healthcare costs primarily caused by neurologic disorders linked to pesticides. They have a half-life estimated at least 10 years, and banning them will not stop them from persisting in the environment for up to 40 years. US studies have shown that their presence in the environment contributes to cognitive delays in young children.
Another area of concern is the rising infertility rates among couples, now affecting around one in five in France. This trend has been linked to the toxicity of EDs on the genital tract, especially in men, and is not only related to increased use of birth control. For example, in sub-Saharan Africa, rates of contraceptive use have increased only marginally, but birth rates have significantly decreased in areas contaminated by waste that is inadequately managed by Western standards.
EDs have also been implicated in the rising incidence of several cancers, including breast cancer in women and prostate cancer in men, and may have contributed to increases in both childhood obesity and adult diabetes.
A Difficult Battle
Chevalier asked: Is the increase in ED contamination inevitable? No, he said, but it is extremely difficult to counter. Governments are reluctant to legislate, particularly when jobs are at stake, even though certain workers are particularly exposed. The ideal situation would be for the public to take matters into their own hands by eliminating EDs from their environment through daily actions that pressure policymakers to act. For example:
- Eliminate plastics (especially for food products) and nonstick coatings
- Reject most cleaning products in favor of traditional solutions (eg, white vinegar and baking soda)
- Avoid imported toys (as producer countries often fail to comply with European health standards)
Environmental charters have been created by several local authorities and regional health agencies. Chevalier urged the public to rely on their recommendations and resources to help drive change.
This story was translated from Univadis France 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.
Endocrine disruptors (EDs) — chemicals in the environment that could affect human endocrine function — are increasingly becoming a prominent concern for the public as well as professionals. At its 40th congress, the French Society of Endocrinology hosted a public lecture on the subject, given by Nicolas Chevalier, MD, PhD, professor of endocrinology at the University Hospital of Nice in France.
Environmental EDs
Chevalier began by asking the audience to remember one number: 906. This is the number of substances identified by the French Agency for Food, Environmental and Occupational Health & Safety for which there are sufficient scientific data to confirm or at least suspect endocrine-disrupting activity. In reality, the number is likely closer to 10,000, he said.
These chemicals include bisphenol A and its substitutes, parabens, phthalates, and pesticides. Additionally, lithium (mainly found in batteries), polychlorinated biphenyls, per- and polyfluoroalkyl substances, and polybromodiphenyl ethers, or brominated flame retardants, are included. These products are found throughout our environment, so much so that Chevalier said: “We are swimming in a soup of endocrine disruptors.”
The main source of human contamination is food, responsible for an estimated 80%-90% of those encountered. They may enter the food supply during production or preservation, and pesticides are not the only culprits. For example, fatty fish contain heavy metals. Water is also a significant source of contamination. It is worth noting that tap water is the cleanest and most monitored type when it comes to EDs. However, plastic bottles leach not only EDs but also microplastics, which are a major environmental pollution source.
Many other features in our daily environment contain EDs: Clothing (especially shoes), nonstick cookware, plastic containers (especially those heated in the microwave), plastic toys (which young children often put in their mouths), and cosmetic products (makeup, which is increasingly used by young girls). The placenta is not the barrier it was once thought to be: Amniotic fluid has been found to contain about 35 molecules that are toxic for the fetus, with at least 11 or 12 exceeding safety thresholds.
Multiple Linked Diseases
An incomplete list of ED-related diseases would include cancer, infertility, obesity, and diabetes, Chevalier said. Are these data alarmist? he asked. After all, life expectancy has increased globally by more than 10 years since the 1970s, and this has occurred alongside the increased use of EDs. However, he suggested remembering a second number: 157. This represents the billions of euros in European healthcare costs primarily caused by neurologic disorders linked to pesticides. They have a half-life estimated at least 10 years, and banning them will not stop them from persisting in the environment for up to 40 years. US studies have shown that their presence in the environment contributes to cognitive delays in young children.
Another area of concern is the rising infertility rates among couples, now affecting around one in five in France. This trend has been linked to the toxicity of EDs on the genital tract, especially in men, and is not only related to increased use of birth control. For example, in sub-Saharan Africa, rates of contraceptive use have increased only marginally, but birth rates have significantly decreased in areas contaminated by waste that is inadequately managed by Western standards.
EDs have also been implicated in the rising incidence of several cancers, including breast cancer in women and prostate cancer in men, and may have contributed to increases in both childhood obesity and adult diabetes.
A Difficult Battle
Chevalier asked: Is the increase in ED contamination inevitable? No, he said, but it is extremely difficult to counter. Governments are reluctant to legislate, particularly when jobs are at stake, even though certain workers are particularly exposed. The ideal situation would be for the public to take matters into their own hands by eliminating EDs from their environment through daily actions that pressure policymakers to act. For example:
- Eliminate plastics (especially for food products) and nonstick coatings
- Reject most cleaning products in favor of traditional solutions (eg, white vinegar and baking soda)
- Avoid imported toys (as producer countries often fail to comply with European health standards)
Environmental charters have been created by several local authorities and regional health agencies. Chevalier urged the public to rely on their recommendations and resources to help drive change.
This story was translated from Univadis France 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.
National Noncompete Ban Unlikely to Survive Under Trump, Experts Say
Even before the presidential election, the Federal Trade Commission’s (FTC) national ban on noncompete clauses faced a tough battle for survival in the courts.
Now, legal specialists forecast a grim prognosis for the ban under Donald Trump’s return to the White House.
But a federal district’s court ruling put the ban on hold, and the Trump administration isn’t expected to support lifting the ban.
“It is likely that the Trump administration will decline to defend the rule and may not even appeal the district court’s ruling, which means that the ban on noncompetes will not go into effect,” Steven Lubet, JD, a professor emeritus at Northwestern University Pritzker School of Law, Chicago, Illinois, said in an interview.
What’s in a Noncompete Clause?
Noncompete clauses in employee contracts typically restrict when and where workers can take future jobs. In medicine, supporters argue that the clauses are fair. Hospitals and practices provide a base of patients to physicians, they say, in return for their agreement not to go work for a competitor.
But those opposed to these clauses argue that the restrictions harm careers and hurt patients by unfairly preventing physicians from moving to new jobs where they’re needed.
At an April meeting, the FTC board voted 3 to 2 to ban noncompete clauses; some nonprofit organizations and senior executives were expected to be exempt. The FTC estimated that the move would save the healthcare system alone as much as $194 billion over 10 years.
“A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” declared FTC Commissioner Alvaro Bedoya.
Hospitals protested the move. In a statement, the general counsel for the American Hospital Association called it “bad law, bad policy, and a clear sign of an agency run amok” and said the FTC ignored “mountains of contrary legal precedent and evidence about its adverse impacts on the health care markets.”
Although the American Medical Association does not support a total ban, its House of Delegates adopted policies in 2023 to support the prohibition of noncompete contracts for physicians employed by for-profit and nonprofit hospitals, hospital systems, or staffing companies.
Texas Federal Judge Intervenes to Halt Ban
The ban was supposed to take effect on Sept. 4, 2024. But Texas federal judge Ada E. Brown struck down the ban in an Aug. 20 decision. She ruled that the FTC went beyond its authority.
“The district court based its ruling on a very dubious distinction between ‘unfair practices,’ which the FTC may prohibit, and ‘unfair competition,’ which, according to the court, it may not,” said Lubet.
In fact, the ban should stand, he said. “This is a classic case of the government intervening on behalf of consumers/patients by prohibiting an unfair and harmful employment practice,” Lubet said.
Amanda Hill, an attorney in Austin, Texas, who trains physicians about how to negotiate contracts, has a different take. “The Federal Trade Commission came down hard, and honestly, it really overstepped,” she said in an interview. “Congress needs to write laws, not regulatory bodies. I think all the lawyers went: ‘Good try, but you’re not going to get anywhere with that.’ ”
She noted that physicians themselves are divided over the value of noncompete clauses. “I would say 80% of my clients can’t stand noncompetes.” But another 20% own their own practices and hate the idea of losing their physicians to competitors, she said.
Trump Isn’t Seen as Likely to Support Ban
While the Biden administration firmly supported a ban on noncompete clauses, there isn’t a strict Democratic-Republican divide over whether the agreements are a good idea. Some red states have embraced bans, and Hill said this can make sense from a Republican point of view: “We don’t want to run doctors out of town and out of the state because they think they’re going to be bound by big hospitals and corporate interests.”
In fact, former Florida congressman Matt Gaetz, a Republican briefly tapped as President-elect Trump’s nominee for attorney general, supports noncompete clauses. He filed a friend-of-the-court brief with the Texas judge that supported the FTC’s ruling, saying it is a “vindication of economic freedom and free enterprise.”
But Republicans generally “believe that federal agencies are going too far and beyond the power granted to them by Congress,” Atlanta, Georgia, attorney Benjamin Fink, Esq., said in an interview.
And Trump is no fan of the FTC and its chair, Lina Khan, who may step down. Observers don’t expect that the Trump administration or a newly constituted FTC board will support an appeal of the Texas judge’s ruling.
“I don’t think anybody else — another agency or a private party — could step in place of the FTC if the FTC declines to defend the ban,” Atlanta attorney Neal F. Weinrich, Esq., said in an interview. In that case, “I think it ends.”
Attorneys Weinrich and Fink work at the same firm, which handles noncompete agreements for physicians.
Noncompete Ban Advocates Turn to States
Even if Kamala Harris had won the presidency, a national ban on noncompete clauses would have faced an uphill battle at the Supreme Court.
“The Supreme Court majority has been unsympathetic to administrative agencies, interpreting their authority very narrowly,” said Lubet.
So what happens to noncompete clauses now? While bipartisan bills in Congress have tried to ban them, legislation is unlikely to pass now that Republicans will control both the House and Senate, Fink said.
According to a recent article, 12 states prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota.
The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in Oregon, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits 2-year noncompetes for “medical specialists” earning over $250,000 annually.
Indiana employers can no longer enter into noncompete agreements with primary care providers. Other specialties may be subject to the clauses, except when the physician terminates the contract for cause or when an employer terminates the contract without cause.
“I definitely think states are going to continue to restrict the use of noncompetes,” Fink said.
Lubet has no disclosures. Hill, Fink, and Weinrich represent physicians in contract negotiations.
A version of this article appeared on Medscape.com.
Even before the presidential election, the Federal Trade Commission’s (FTC) national ban on noncompete clauses faced a tough battle for survival in the courts.
Now, legal specialists forecast a grim prognosis for the ban under Donald Trump’s return to the White House.
But a federal district’s court ruling put the ban on hold, and the Trump administration isn’t expected to support lifting the ban.
“It is likely that the Trump administration will decline to defend the rule and may not even appeal the district court’s ruling, which means that the ban on noncompetes will not go into effect,” Steven Lubet, JD, a professor emeritus at Northwestern University Pritzker School of Law, Chicago, Illinois, said in an interview.
What’s in a Noncompete Clause?
Noncompete clauses in employee contracts typically restrict when and where workers can take future jobs. In medicine, supporters argue that the clauses are fair. Hospitals and practices provide a base of patients to physicians, they say, in return for their agreement not to go work for a competitor.
But those opposed to these clauses argue that the restrictions harm careers and hurt patients by unfairly preventing physicians from moving to new jobs where they’re needed.
At an April meeting, the FTC board voted 3 to 2 to ban noncompete clauses; some nonprofit organizations and senior executives were expected to be exempt. The FTC estimated that the move would save the healthcare system alone as much as $194 billion over 10 years.
“A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” declared FTC Commissioner Alvaro Bedoya.
Hospitals protested the move. In a statement, the general counsel for the American Hospital Association called it “bad law, bad policy, and a clear sign of an agency run amok” and said the FTC ignored “mountains of contrary legal precedent and evidence about its adverse impacts on the health care markets.”
Although the American Medical Association does not support a total ban, its House of Delegates adopted policies in 2023 to support the prohibition of noncompete contracts for physicians employed by for-profit and nonprofit hospitals, hospital systems, or staffing companies.
Texas Federal Judge Intervenes to Halt Ban
The ban was supposed to take effect on Sept. 4, 2024. But Texas federal judge Ada E. Brown struck down the ban in an Aug. 20 decision. She ruled that the FTC went beyond its authority.
“The district court based its ruling on a very dubious distinction between ‘unfair practices,’ which the FTC may prohibit, and ‘unfair competition,’ which, according to the court, it may not,” said Lubet.
In fact, the ban should stand, he said. “This is a classic case of the government intervening on behalf of consumers/patients by prohibiting an unfair and harmful employment practice,” Lubet said.
Amanda Hill, an attorney in Austin, Texas, who trains physicians about how to negotiate contracts, has a different take. “The Federal Trade Commission came down hard, and honestly, it really overstepped,” she said in an interview. “Congress needs to write laws, not regulatory bodies. I think all the lawyers went: ‘Good try, but you’re not going to get anywhere with that.’ ”
She noted that physicians themselves are divided over the value of noncompete clauses. “I would say 80% of my clients can’t stand noncompetes.” But another 20% own their own practices and hate the idea of losing their physicians to competitors, she said.
Trump Isn’t Seen as Likely to Support Ban
While the Biden administration firmly supported a ban on noncompete clauses, there isn’t a strict Democratic-Republican divide over whether the agreements are a good idea. Some red states have embraced bans, and Hill said this can make sense from a Republican point of view: “We don’t want to run doctors out of town and out of the state because they think they’re going to be bound by big hospitals and corporate interests.”
In fact, former Florida congressman Matt Gaetz, a Republican briefly tapped as President-elect Trump’s nominee for attorney general, supports noncompete clauses. He filed a friend-of-the-court brief with the Texas judge that supported the FTC’s ruling, saying it is a “vindication of economic freedom and free enterprise.”
But Republicans generally “believe that federal agencies are going too far and beyond the power granted to them by Congress,” Atlanta, Georgia, attorney Benjamin Fink, Esq., said in an interview.
And Trump is no fan of the FTC and its chair, Lina Khan, who may step down. Observers don’t expect that the Trump administration or a newly constituted FTC board will support an appeal of the Texas judge’s ruling.
“I don’t think anybody else — another agency or a private party — could step in place of the FTC if the FTC declines to defend the ban,” Atlanta attorney Neal F. Weinrich, Esq., said in an interview. In that case, “I think it ends.”
Attorneys Weinrich and Fink work at the same firm, which handles noncompete agreements for physicians.
Noncompete Ban Advocates Turn to States
Even if Kamala Harris had won the presidency, a national ban on noncompete clauses would have faced an uphill battle at the Supreme Court.
“The Supreme Court majority has been unsympathetic to administrative agencies, interpreting their authority very narrowly,” said Lubet.
So what happens to noncompete clauses now? While bipartisan bills in Congress have tried to ban them, legislation is unlikely to pass now that Republicans will control both the House and Senate, Fink said.
According to a recent article, 12 states prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota.
The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in Oregon, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits 2-year noncompetes for “medical specialists” earning over $250,000 annually.
Indiana employers can no longer enter into noncompete agreements with primary care providers. Other specialties may be subject to the clauses, except when the physician terminates the contract for cause or when an employer terminates the contract without cause.
“I definitely think states are going to continue to restrict the use of noncompetes,” Fink said.
Lubet has no disclosures. Hill, Fink, and Weinrich represent physicians in contract negotiations.
A version of this article appeared on Medscape.com.
Even before the presidential election, the Federal Trade Commission’s (FTC) national ban on noncompete clauses faced a tough battle for survival in the courts.
Now, legal specialists forecast a grim prognosis for the ban under Donald Trump’s return to the White House.
But a federal district’s court ruling put the ban on hold, and the Trump administration isn’t expected to support lifting the ban.
“It is likely that the Trump administration will decline to defend the rule and may not even appeal the district court’s ruling, which means that the ban on noncompetes will not go into effect,” Steven Lubet, JD, a professor emeritus at Northwestern University Pritzker School of Law, Chicago, Illinois, said in an interview.
What’s in a Noncompete Clause?
Noncompete clauses in employee contracts typically restrict when and where workers can take future jobs. In medicine, supporters argue that the clauses are fair. Hospitals and practices provide a base of patients to physicians, they say, in return for their agreement not to go work for a competitor.
But those opposed to these clauses argue that the restrictions harm careers and hurt patients by unfairly preventing physicians from moving to new jobs where they’re needed.
At an April meeting, the FTC board voted 3 to 2 to ban noncompete clauses; some nonprofit organizations and senior executives were expected to be exempt. The FTC estimated that the move would save the healthcare system alone as much as $194 billion over 10 years.
“A pandemic killed a million people in this country, and there are doctors who cannot work because of a noncompete,” declared FTC Commissioner Alvaro Bedoya.
Hospitals protested the move. In a statement, the general counsel for the American Hospital Association called it “bad law, bad policy, and a clear sign of an agency run amok” and said the FTC ignored “mountains of contrary legal precedent and evidence about its adverse impacts on the health care markets.”
Although the American Medical Association does not support a total ban, its House of Delegates adopted policies in 2023 to support the prohibition of noncompete contracts for physicians employed by for-profit and nonprofit hospitals, hospital systems, or staffing companies.
Texas Federal Judge Intervenes to Halt Ban
The ban was supposed to take effect on Sept. 4, 2024. But Texas federal judge Ada E. Brown struck down the ban in an Aug. 20 decision. She ruled that the FTC went beyond its authority.
“The district court based its ruling on a very dubious distinction between ‘unfair practices,’ which the FTC may prohibit, and ‘unfair competition,’ which, according to the court, it may not,” said Lubet.
In fact, the ban should stand, he said. “This is a classic case of the government intervening on behalf of consumers/patients by prohibiting an unfair and harmful employment practice,” Lubet said.
Amanda Hill, an attorney in Austin, Texas, who trains physicians about how to negotiate contracts, has a different take. “The Federal Trade Commission came down hard, and honestly, it really overstepped,” she said in an interview. “Congress needs to write laws, not regulatory bodies. I think all the lawyers went: ‘Good try, but you’re not going to get anywhere with that.’ ”
She noted that physicians themselves are divided over the value of noncompete clauses. “I would say 80% of my clients can’t stand noncompetes.” But another 20% own their own practices and hate the idea of losing their physicians to competitors, she said.
Trump Isn’t Seen as Likely to Support Ban
While the Biden administration firmly supported a ban on noncompete clauses, there isn’t a strict Democratic-Republican divide over whether the agreements are a good idea. Some red states have embraced bans, and Hill said this can make sense from a Republican point of view: “We don’t want to run doctors out of town and out of the state because they think they’re going to be bound by big hospitals and corporate interests.”
In fact, former Florida congressman Matt Gaetz, a Republican briefly tapped as President-elect Trump’s nominee for attorney general, supports noncompete clauses. He filed a friend-of-the-court brief with the Texas judge that supported the FTC’s ruling, saying it is a “vindication of economic freedom and free enterprise.”
But Republicans generally “believe that federal agencies are going too far and beyond the power granted to them by Congress,” Atlanta, Georgia, attorney Benjamin Fink, Esq., said in an interview.
And Trump is no fan of the FTC and its chair, Lina Khan, who may step down. Observers don’t expect that the Trump administration or a newly constituted FTC board will support an appeal of the Texas judge’s ruling.
“I don’t think anybody else — another agency or a private party — could step in place of the FTC if the FTC declines to defend the ban,” Atlanta attorney Neal F. Weinrich, Esq., said in an interview. In that case, “I think it ends.”
Attorneys Weinrich and Fink work at the same firm, which handles noncompete agreements for physicians.
Noncompete Ban Advocates Turn to States
Even if Kamala Harris had won the presidency, a national ban on noncompete clauses would have faced an uphill battle at the Supreme Court.
“The Supreme Court majority has been unsympathetic to administrative agencies, interpreting their authority very narrowly,” said Lubet.
So what happens to noncompete clauses now? While bipartisan bills in Congress have tried to ban them, legislation is unlikely to pass now that Republicans will control both the House and Senate, Fink said.
According to a recent article, 12 states prohibit noncompete clauses for physicians: Alabama, California, Colorado, Delaware, Massachusetts, Montana, New Hampshire, New Mexico, North Dakota, Oklahoma, Rhode Island, and South Dakota.
The remaining states allow noncompetes in some form, often excluding them for employees earning below a certain threshold. For example, in Oregon, noncompete agreements may apply to employees earning more than $113,241. Most states have provisions to adjust the threshold annually. The District of Columbia permits 2-year noncompetes for “medical specialists” earning over $250,000 annually.
Indiana employers can no longer enter into noncompete agreements with primary care providers. Other specialties may be subject to the clauses, except when the physician terminates the contract for cause or when an employer terminates the contract without cause.
“I definitely think states are going to continue to restrict the use of noncompetes,” Fink said.
Lubet has no disclosures. Hill, Fink, and Weinrich represent physicians in contract negotiations.
A version of this article appeared on Medscape.com.
US Study Pinpoints Merkel Cell Risk Factors
TOPLINE:
in the United States.
METHODOLOGY:
- Researchers evaluated 38,020 MCC cases (38% women; 93% non-Hispanic White, 4% Hispanic, 1% non-Hispanic Black) diagnosed in the United States from 2001 to 2019 to estimate the contribution of potentially modifiable risk factors to the burden of MCC.
- Population-based cancer registries and linkages with HIV and transplant registries were utilized to identify MCC cases in patients with HIV, solid organ transplant recipients, and patients with chronic lymphocytic leukemia (CLL).
- Data on cloud-adjusted daily ambient UVR irradiance were merged with cancer registry information on the county of residence at diagnosis to assess UVR exposure. Studies reporting the prevalence of MCPyV in MCC specimens collected in the United States were combined via a meta-analysis.
- The study assessed population attributable fractions of MCC cases that were attributable to major immunosuppressive conditions (HIV, solid organ transplant, and chronic CLL), ambient UVR exposure, and MCPyV.
TAKEAWAY:
- The incidence of MCC was higher in people with HIV (standardized incidence ratio [SIR], 2.78), organ transplant recipients (SIR, 13.1), and patients with CLL (SIR, 5.75) than in the general US population. However, only 2.5% of MCC cases were attributable to these immunosuppressive conditions.
- Non-Hispanic White individuals showed elevated MCC incidence at both lower and higher ambient UVR exposure levels, with incidence rate ratios of 4.05 and 4.91, respectively, for MCC on the head and neck.
- A meta-analysis of 19 case series revealed that 63.8% of MCC cases were attributable to MCPyV, with a similar prevalence observed between immunocompromised and immunocompetent patients.
- Overall, 65.1% of MCC cases were attributable to ambient UVR exposure, with higher attribution for cases diagnosed on the head and neck than those diagnosed on other sites (72.1% vs 60.2%).
IN PRACTICE:
“The results of this study suggest that most MCC cases in the US are attributable to MCPyV and/or ambient UVR [UV radiation] exposure, with a smaller fraction attributable to three major immunosuppressive conditions,” the authors wrote. “Future studies should investigate UVR mutational signature, TMB [tumor mutational burden], and MCPyV prevalence according to race and ethnicity and patient immune status to help clarify the overlap between MCC risk factors.”
SOURCE:
The study was led by Jacob T. Tribble, BA, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), Rockville, Maryland. It was published online on November 27, 2024, in JAMA Dermatology.
LIMITATIONS:
Incidences of MCC may have been inflated because of increased medical surveillance in immunosuppressed populations. The analysis assumed that only cases among non-Hispanic White individuals were associated with UVR. Additionally, the meta-analysis of MCPyV prevalence primarily included studies from large academic institutions, which may not be representative of the entire US population.
DISCLOSURES:
This study was supported in part by the Intramural Research Program of the NCI and the National Institutes of Health Medical Research Scholars Program. Additional funding was provided through a public-private partnership with contributions from the American Association for Dental Research and the Colgate-Palmolive Company to the Foundation for the National Institutes of Health. The authors reported no relevant conflicts of interest.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
in the United States.
METHODOLOGY:
- Researchers evaluated 38,020 MCC cases (38% women; 93% non-Hispanic White, 4% Hispanic, 1% non-Hispanic Black) diagnosed in the United States from 2001 to 2019 to estimate the contribution of potentially modifiable risk factors to the burden of MCC.
- Population-based cancer registries and linkages with HIV and transplant registries were utilized to identify MCC cases in patients with HIV, solid organ transplant recipients, and patients with chronic lymphocytic leukemia (CLL).
- Data on cloud-adjusted daily ambient UVR irradiance were merged with cancer registry information on the county of residence at diagnosis to assess UVR exposure. Studies reporting the prevalence of MCPyV in MCC specimens collected in the United States were combined via a meta-analysis.
- The study assessed population attributable fractions of MCC cases that were attributable to major immunosuppressive conditions (HIV, solid organ transplant, and chronic CLL), ambient UVR exposure, and MCPyV.
TAKEAWAY:
- The incidence of MCC was higher in people with HIV (standardized incidence ratio [SIR], 2.78), organ transplant recipients (SIR, 13.1), and patients with CLL (SIR, 5.75) than in the general US population. However, only 2.5% of MCC cases were attributable to these immunosuppressive conditions.
- Non-Hispanic White individuals showed elevated MCC incidence at both lower and higher ambient UVR exposure levels, with incidence rate ratios of 4.05 and 4.91, respectively, for MCC on the head and neck.
- A meta-analysis of 19 case series revealed that 63.8% of MCC cases were attributable to MCPyV, with a similar prevalence observed between immunocompromised and immunocompetent patients.
- Overall, 65.1% of MCC cases were attributable to ambient UVR exposure, with higher attribution for cases diagnosed on the head and neck than those diagnosed on other sites (72.1% vs 60.2%).
IN PRACTICE:
“The results of this study suggest that most MCC cases in the US are attributable to MCPyV and/or ambient UVR [UV radiation] exposure, with a smaller fraction attributable to three major immunosuppressive conditions,” the authors wrote. “Future studies should investigate UVR mutational signature, TMB [tumor mutational burden], and MCPyV prevalence according to race and ethnicity and patient immune status to help clarify the overlap between MCC risk factors.”
SOURCE:
The study was led by Jacob T. Tribble, BA, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), Rockville, Maryland. It was published online on November 27, 2024, in JAMA Dermatology.
LIMITATIONS:
Incidences of MCC may have been inflated because of increased medical surveillance in immunosuppressed populations. The analysis assumed that only cases among non-Hispanic White individuals were associated with UVR. Additionally, the meta-analysis of MCPyV prevalence primarily included studies from large academic institutions, which may not be representative of the entire US population.
DISCLOSURES:
This study was supported in part by the Intramural Research Program of the NCI and the National Institutes of Health Medical Research Scholars Program. Additional funding was provided through a public-private partnership with contributions from the American Association for Dental Research and the Colgate-Palmolive Company to the Foundation for the National Institutes of Health. The authors reported no relevant conflicts of interest.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
in the United States.
METHODOLOGY:
- Researchers evaluated 38,020 MCC cases (38% women; 93% non-Hispanic White, 4% Hispanic, 1% non-Hispanic Black) diagnosed in the United States from 2001 to 2019 to estimate the contribution of potentially modifiable risk factors to the burden of MCC.
- Population-based cancer registries and linkages with HIV and transplant registries were utilized to identify MCC cases in patients with HIV, solid organ transplant recipients, and patients with chronic lymphocytic leukemia (CLL).
- Data on cloud-adjusted daily ambient UVR irradiance were merged with cancer registry information on the county of residence at diagnosis to assess UVR exposure. Studies reporting the prevalence of MCPyV in MCC specimens collected in the United States were combined via a meta-analysis.
- The study assessed population attributable fractions of MCC cases that were attributable to major immunosuppressive conditions (HIV, solid organ transplant, and chronic CLL), ambient UVR exposure, and MCPyV.
TAKEAWAY:
- The incidence of MCC was higher in people with HIV (standardized incidence ratio [SIR], 2.78), organ transplant recipients (SIR, 13.1), and patients with CLL (SIR, 5.75) than in the general US population. However, only 2.5% of MCC cases were attributable to these immunosuppressive conditions.
- Non-Hispanic White individuals showed elevated MCC incidence at both lower and higher ambient UVR exposure levels, with incidence rate ratios of 4.05 and 4.91, respectively, for MCC on the head and neck.
- A meta-analysis of 19 case series revealed that 63.8% of MCC cases were attributable to MCPyV, with a similar prevalence observed between immunocompromised and immunocompetent patients.
- Overall, 65.1% of MCC cases were attributable to ambient UVR exposure, with higher attribution for cases diagnosed on the head and neck than those diagnosed on other sites (72.1% vs 60.2%).
IN PRACTICE:
“The results of this study suggest that most MCC cases in the US are attributable to MCPyV and/or ambient UVR [UV radiation] exposure, with a smaller fraction attributable to three major immunosuppressive conditions,” the authors wrote. “Future studies should investigate UVR mutational signature, TMB [tumor mutational burden], and MCPyV prevalence according to race and ethnicity and patient immune status to help clarify the overlap between MCC risk factors.”
SOURCE:
The study was led by Jacob T. Tribble, BA, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), Rockville, Maryland. It was published online on November 27, 2024, in JAMA Dermatology.
LIMITATIONS:
Incidences of MCC may have been inflated because of increased medical surveillance in immunosuppressed populations. The analysis assumed that only cases among non-Hispanic White individuals were associated with UVR. Additionally, the meta-analysis of MCPyV prevalence primarily included studies from large academic institutions, which may not be representative of the entire US population.
DISCLOSURES:
This study was supported in part by the Intramural Research Program of the NCI and the National Institutes of Health Medical Research Scholars Program. Additional funding was provided through a public-private partnership with contributions from the American Association for Dental Research and the Colgate-Palmolive Company to the Foundation for the National Institutes of Health. The authors reported no relevant conflicts of interest.
This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Watch That Attitude: Is There Ageism in Healthcare?
People are living longer in Europe. Life expectancy increased on the continent by around 12 years between 1960 and 2022. And despite slower progress during the COVID-19 pandemic, the trend appears to be continuing.
Not only are Europeans living longer, their fertility rates are declining. This means that the number of people aged 75-84 years is projected to grow in Europe a full 56.1% by 2050, while the population younger than 55 years is expected to fall by 13.5%.
This means that attitudes toward age need to change, and fast — even among healthcare professionals.
Healthcare Is Not Exempt From Ageist Attitudes
A systematic review published in the journal PLOS ONE in 2020 found that age was a determinant factor in dictating who received certain medical procedures or treatments. For example, a study of 9105 hospitalized patients found that healthcare providers were significantly more likely to withhold life-sustaining treatments from older patients. Another study found evidence that older people are excluded from clinical trials, even when the trials are for diseases that appear later in life, like Parkinson’s.
“In healthcare, there are different levels of ageism,” explained Hannah Swift, PhD, reader in social and organizational psychology at the University of Kent in the United Kingdom.
Ageism is embedded in the laws, rules, and practices of institutions, she explained. This became especially obvious during the pandemic, when health professionals had to decide who to treat, possibly using age as a proxy for making some of these decisions, she said.
“When you categorize people, you might be using stereotypes, assumptions, and expectations about age and that age group to make those decisions, and that’s where errors can occur.”
She added that ageist attitudes also become apparent at the interpersonal level by using patronizing language or offering unnecessary help to older people based on assumptions about their cognitive and physical abilities.
“Older age is often wrongly associated with declining levels of health and activity,” said Ittay Mannheim, PhD, guest postdoctoral researcher on aging and ageism at the Open University of the Netherlands. “However, older adults are a very diverse group, varying widely in many aspects, including health conditions. This stereotype can influence how healthcare professionals interact with them, assuming frailty or memory issues simply based on age. It’s important to recognize that being older doesn’t necessarily mean being ill.”
Mannheim’s research found that healthcare professionals often stand in the way of older people using technology-based treatments due to negative attitudes towards age. “So, actually, a barrier to using these technologies could be that healthcare professionals don’t think that someone can use it or won’t even offer it because someone looks old or is old,” he said.
The Impacts
Discrimination impacts the physical, mental, and social well-being of its victims. This includes attitudes towards age.
The PLOS ONE review of research on the global reach of ageism found that experienced or self-determined ageism was associated with significantly worse health outcomes across all countries examined. The same research team calculated that an estimated 6.3 million cases of depression worldwide are linked to ageism.
Other research has found that exposure to negative age stereotyping impacts willingness to adopt a healthy lifestyle in addition to increasing the risk for cardiovascular events.
What Can Be Done?
“Healthcare professionals frequently interact with older adults at their most vulnerable, which can reinforce negative stereotypes of older people being vulnerable or ill,” said Swift. “However, not all older adults fit these stereotypes. Many can live well and independently. Perhaps healthcare education should include reminders of the diverse experiences of older individuals rather than solely focusing on the moments when they require help.”
Research indicates that although progress has been made in geriatric training and the care of older individuals by healthcare education institutions, improved education and training are still needed at all levels of geriatric healthcare, including hospital administrators, physicians, nurses, personal caregivers, and associated health professions.
“Generally speaking, what healthcare professionals learn about aging tends to focus more on the biological aspects,” said Mannheim. “However, they may not fully understand what it means to be old or how to interact with older individuals, especially regarding technology. It is important to raise awareness about ageism because, in my experience working with healthcare professionals, even a single workshop on ageism can have a profound impact. Participants often respond with surprise, saying something like, ‘Wow, I never thought about this before.’”
Mannheim said that training healthcare providers to understand the aging process better could help to reduce any biases they might have and better prepare them to respond more adequately to the needs of older patients.
“We cannot devalue the lives of older people simply because they are older. It is crucial for all of us, especially governments, to acknowledge our responsibility to protect and promote human rights for individuals of all ages. If we fail to do this, the strategies we’ve witnessed during this pandemic will be repeated in the future,” said Nena Georgantzi, PhD, Barcelona-based human rights manager at AGE Platform Europe, an EU network of organizations of and for older people.
A version of this article appeared on Medscape.com.
People are living longer in Europe. Life expectancy increased on the continent by around 12 years between 1960 and 2022. And despite slower progress during the COVID-19 pandemic, the trend appears to be continuing.
Not only are Europeans living longer, their fertility rates are declining. This means that the number of people aged 75-84 years is projected to grow in Europe a full 56.1% by 2050, while the population younger than 55 years is expected to fall by 13.5%.
This means that attitudes toward age need to change, and fast — even among healthcare professionals.
Healthcare Is Not Exempt From Ageist Attitudes
A systematic review published in the journal PLOS ONE in 2020 found that age was a determinant factor in dictating who received certain medical procedures or treatments. For example, a study of 9105 hospitalized patients found that healthcare providers were significantly more likely to withhold life-sustaining treatments from older patients. Another study found evidence that older people are excluded from clinical trials, even when the trials are for diseases that appear later in life, like Parkinson’s.
“In healthcare, there are different levels of ageism,” explained Hannah Swift, PhD, reader in social and organizational psychology at the University of Kent in the United Kingdom.
Ageism is embedded in the laws, rules, and practices of institutions, she explained. This became especially obvious during the pandemic, when health professionals had to decide who to treat, possibly using age as a proxy for making some of these decisions, she said.
“When you categorize people, you might be using stereotypes, assumptions, and expectations about age and that age group to make those decisions, and that’s where errors can occur.”
She added that ageist attitudes also become apparent at the interpersonal level by using patronizing language or offering unnecessary help to older people based on assumptions about their cognitive and physical abilities.
“Older age is often wrongly associated with declining levels of health and activity,” said Ittay Mannheim, PhD, guest postdoctoral researcher on aging and ageism at the Open University of the Netherlands. “However, older adults are a very diverse group, varying widely in many aspects, including health conditions. This stereotype can influence how healthcare professionals interact with them, assuming frailty or memory issues simply based on age. It’s important to recognize that being older doesn’t necessarily mean being ill.”
Mannheim’s research found that healthcare professionals often stand in the way of older people using technology-based treatments due to negative attitudes towards age. “So, actually, a barrier to using these technologies could be that healthcare professionals don’t think that someone can use it or won’t even offer it because someone looks old or is old,” he said.
The Impacts
Discrimination impacts the physical, mental, and social well-being of its victims. This includes attitudes towards age.
The PLOS ONE review of research on the global reach of ageism found that experienced or self-determined ageism was associated with significantly worse health outcomes across all countries examined. The same research team calculated that an estimated 6.3 million cases of depression worldwide are linked to ageism.
Other research has found that exposure to negative age stereotyping impacts willingness to adopt a healthy lifestyle in addition to increasing the risk for cardiovascular events.
What Can Be Done?
“Healthcare professionals frequently interact with older adults at their most vulnerable, which can reinforce negative stereotypes of older people being vulnerable or ill,” said Swift. “However, not all older adults fit these stereotypes. Many can live well and independently. Perhaps healthcare education should include reminders of the diverse experiences of older individuals rather than solely focusing on the moments when they require help.”
Research indicates that although progress has been made in geriatric training and the care of older individuals by healthcare education institutions, improved education and training are still needed at all levels of geriatric healthcare, including hospital administrators, physicians, nurses, personal caregivers, and associated health professions.
“Generally speaking, what healthcare professionals learn about aging tends to focus more on the biological aspects,” said Mannheim. “However, they may not fully understand what it means to be old or how to interact with older individuals, especially regarding technology. It is important to raise awareness about ageism because, in my experience working with healthcare professionals, even a single workshop on ageism can have a profound impact. Participants often respond with surprise, saying something like, ‘Wow, I never thought about this before.’”
Mannheim said that training healthcare providers to understand the aging process better could help to reduce any biases they might have and better prepare them to respond more adequately to the needs of older patients.
“We cannot devalue the lives of older people simply because they are older. It is crucial for all of us, especially governments, to acknowledge our responsibility to protect and promote human rights for individuals of all ages. If we fail to do this, the strategies we’ve witnessed during this pandemic will be repeated in the future,” said Nena Georgantzi, PhD, Barcelona-based human rights manager at AGE Platform Europe, an EU network of organizations of and for older people.
A version of this article appeared on Medscape.com.
People are living longer in Europe. Life expectancy increased on the continent by around 12 years between 1960 and 2022. And despite slower progress during the COVID-19 pandemic, the trend appears to be continuing.
Not only are Europeans living longer, their fertility rates are declining. This means that the number of people aged 75-84 years is projected to grow in Europe a full 56.1% by 2050, while the population younger than 55 years is expected to fall by 13.5%.
This means that attitudes toward age need to change, and fast — even among healthcare professionals.
Healthcare Is Not Exempt From Ageist Attitudes
A systematic review published in the journal PLOS ONE in 2020 found that age was a determinant factor in dictating who received certain medical procedures or treatments. For example, a study of 9105 hospitalized patients found that healthcare providers were significantly more likely to withhold life-sustaining treatments from older patients. Another study found evidence that older people are excluded from clinical trials, even when the trials are for diseases that appear later in life, like Parkinson’s.
“In healthcare, there are different levels of ageism,” explained Hannah Swift, PhD, reader in social and organizational psychology at the University of Kent in the United Kingdom.
Ageism is embedded in the laws, rules, and practices of institutions, she explained. This became especially obvious during the pandemic, when health professionals had to decide who to treat, possibly using age as a proxy for making some of these decisions, she said.
“When you categorize people, you might be using stereotypes, assumptions, and expectations about age and that age group to make those decisions, and that’s where errors can occur.”
She added that ageist attitudes also become apparent at the interpersonal level by using patronizing language or offering unnecessary help to older people based on assumptions about their cognitive and physical abilities.
“Older age is often wrongly associated with declining levels of health and activity,” said Ittay Mannheim, PhD, guest postdoctoral researcher on aging and ageism at the Open University of the Netherlands. “However, older adults are a very diverse group, varying widely in many aspects, including health conditions. This stereotype can influence how healthcare professionals interact with them, assuming frailty or memory issues simply based on age. It’s important to recognize that being older doesn’t necessarily mean being ill.”
Mannheim’s research found that healthcare professionals often stand in the way of older people using technology-based treatments due to negative attitudes towards age. “So, actually, a barrier to using these technologies could be that healthcare professionals don’t think that someone can use it or won’t even offer it because someone looks old or is old,” he said.
The Impacts
Discrimination impacts the physical, mental, and social well-being of its victims. This includes attitudes towards age.
The PLOS ONE review of research on the global reach of ageism found that experienced or self-determined ageism was associated with significantly worse health outcomes across all countries examined. The same research team calculated that an estimated 6.3 million cases of depression worldwide are linked to ageism.
Other research has found that exposure to negative age stereotyping impacts willingness to adopt a healthy lifestyle in addition to increasing the risk for cardiovascular events.
What Can Be Done?
“Healthcare professionals frequently interact with older adults at their most vulnerable, which can reinforce negative stereotypes of older people being vulnerable or ill,” said Swift. “However, not all older adults fit these stereotypes. Many can live well and independently. Perhaps healthcare education should include reminders of the diverse experiences of older individuals rather than solely focusing on the moments when they require help.”
Research indicates that although progress has been made in geriatric training and the care of older individuals by healthcare education institutions, improved education and training are still needed at all levels of geriatric healthcare, including hospital administrators, physicians, nurses, personal caregivers, and associated health professions.
“Generally speaking, what healthcare professionals learn about aging tends to focus more on the biological aspects,” said Mannheim. “However, they may not fully understand what it means to be old or how to interact with older individuals, especially regarding technology. It is important to raise awareness about ageism because, in my experience working with healthcare professionals, even a single workshop on ageism can have a profound impact. Participants often respond with surprise, saying something like, ‘Wow, I never thought about this before.’”
Mannheim said that training healthcare providers to understand the aging process better could help to reduce any biases they might have and better prepare them to respond more adequately to the needs of older patients.
“We cannot devalue the lives of older people simply because they are older. It is crucial for all of us, especially governments, to acknowledge our responsibility to protect and promote human rights for individuals of all ages. If we fail to do this, the strategies we’ve witnessed during this pandemic will be repeated in the future,” said Nena Georgantzi, PhD, Barcelona-based human rights manager at AGE Platform Europe, an EU network of organizations of and for older people.
A version of this article appeared on Medscape.com.
Does Screening at 40-49 Years Boost Breast Cancer Survival?
The data call into question draft guidelines from the Canadian Task Force on Preventive Health Care, which suggest not systematically screening women in this age group with mammography.
Overdiagnosis Challenged
Given that some jurisdictions in Canada have organized screening programs and some do not, there was an opportunity to compare breast cancer 10-year net survival of women who lived in jurisdictions with and without such programs, explained family physician Anna N. Wilkinson, MD, Ottawa regional cancer primary care lead and associate professor at the University of Ottawa in Ontario, Canada.
“The question was [whether] we could use big cancer data to figure out what’s going on,” she told this news organization.
To investigate, Wilkinson and co-investigators reviewed data from the Canadian Cancer Registry linked to mortality information and assessed outcomes for women aged 40-49 and 50-59 years diagnosed with breast cancer from 2002 to 2007. They compared 10-year net survival estimates in jurisdictions with organized screening programs for those aged 40-49 years with the jurisdictions without them.
“Net survival is important because it’s a survival measure that looks at only the cancer in question,” Wilkinson explained.
Investigators determined breast cancer to be the primary cause of 10-year mortality in women aged 40-49 years diagnosed with the disease (90.7% of deaths).
Furthermore, the 10-year net survival in jurisdictions that screened these women (84.8%) was 1.9 percentage points higher than for jurisdictions that did not (82.9%).
The difference in 10-year net survival favoring jurisdictions that offered screening was significant for women aged 45-49 years (2.6 percentage points) but not for those aged 40-44 years (0.9 percentage points).
Given that 90% of the deaths in women in their 40s who had a breast cancer diagnosis were due to breast cancer, Wilkinson challenged the concept of women in their 40s being overdiagnosed with breast cancer, meaning that the cancers detected were indolent and did not require treatment nor result in death.
Earlier detection would generally mean finding disease at an earlier stage and the need for less invasive treatment, she noted. “And one of the biggest benefits [of screening women in their 40s] is that you have diagnosis at earlier stage disease, which means fewer intensive therapies, less time off work, less long-term morbidity, and less cost to our healthcare system.”
Modeling Shows Little Screening Benefit
The task force’s draft guidelines, released earlier this year, were based on evidence from 165 studies including randomized, controlled trials, observational studies, time-trend studies and modeling. They suggest not systematically screening women 40-49 with mammography who are not high risk.
Family physician Guylène Thériault, MD, chair of the task force and its breast cancer working group, and director of the Pedagogy Center at the Outaouais Campus, McGill University, Montreal, Quebec, Canada, explained that to come to that conclusion, the task force had assessed the impact of organized screening for women in Canada aged 40-49 years and calculated the impact of mammography for every 1000 women over 10 years.
The model suggested that screening would yield 368 false positives, leading to 55 biopsies, and then to a breast cancer diagnosis in 19 women. Of those 19, the task force estimated 17 or 18 would not die of breast cancer over 10 years, two would be treated for breast cancer that would not have caused problems, ie, overdiagnosis, and one to two would die of breast cancer.
Without screening, on the other hand, the model suggested that 983 of 1000 women aged 40-49 years would not be diagnosed with breast cancer, and 17 would be, 15 of whom would not die from breast cancer over 10 years (no overdiagnosis, no deaths prevented) and two would die.
It is important that family physicians provide their patients with this information to assist in shared decision making about screening, Thériault said.
Wilkinson concluded that screening programs that included women in their 40s were associated with a significantly higher breast cancer 10-year survival, without an increased rate of diagnosis. She suggested that the study findings can inform the screening guidelines for women aged 40-49 years.
The study was supported by the University of Ottawa’s department of family medicine.
Wilkinson, MD, is a consultant for Thrive Health. Thériault, MD, disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
The data call into question draft guidelines from the Canadian Task Force on Preventive Health Care, which suggest not systematically screening women in this age group with mammography.
Overdiagnosis Challenged
Given that some jurisdictions in Canada have organized screening programs and some do not, there was an opportunity to compare breast cancer 10-year net survival of women who lived in jurisdictions with and without such programs, explained family physician Anna N. Wilkinson, MD, Ottawa regional cancer primary care lead and associate professor at the University of Ottawa in Ontario, Canada.
“The question was [whether] we could use big cancer data to figure out what’s going on,” she told this news organization.
To investigate, Wilkinson and co-investigators reviewed data from the Canadian Cancer Registry linked to mortality information and assessed outcomes for women aged 40-49 and 50-59 years diagnosed with breast cancer from 2002 to 2007. They compared 10-year net survival estimates in jurisdictions with organized screening programs for those aged 40-49 years with the jurisdictions without them.
“Net survival is important because it’s a survival measure that looks at only the cancer in question,” Wilkinson explained.
Investigators determined breast cancer to be the primary cause of 10-year mortality in women aged 40-49 years diagnosed with the disease (90.7% of deaths).
Furthermore, the 10-year net survival in jurisdictions that screened these women (84.8%) was 1.9 percentage points higher than for jurisdictions that did not (82.9%).
The difference in 10-year net survival favoring jurisdictions that offered screening was significant for women aged 45-49 years (2.6 percentage points) but not for those aged 40-44 years (0.9 percentage points).
Given that 90% of the deaths in women in their 40s who had a breast cancer diagnosis were due to breast cancer, Wilkinson challenged the concept of women in their 40s being overdiagnosed with breast cancer, meaning that the cancers detected were indolent and did not require treatment nor result in death.
Earlier detection would generally mean finding disease at an earlier stage and the need for less invasive treatment, she noted. “And one of the biggest benefits [of screening women in their 40s] is that you have diagnosis at earlier stage disease, which means fewer intensive therapies, less time off work, less long-term morbidity, and less cost to our healthcare system.”
Modeling Shows Little Screening Benefit
The task force’s draft guidelines, released earlier this year, were based on evidence from 165 studies including randomized, controlled trials, observational studies, time-trend studies and modeling. They suggest not systematically screening women 40-49 with mammography who are not high risk.
Family physician Guylène Thériault, MD, chair of the task force and its breast cancer working group, and director of the Pedagogy Center at the Outaouais Campus, McGill University, Montreal, Quebec, Canada, explained that to come to that conclusion, the task force had assessed the impact of organized screening for women in Canada aged 40-49 years and calculated the impact of mammography for every 1000 women over 10 years.
The model suggested that screening would yield 368 false positives, leading to 55 biopsies, and then to a breast cancer diagnosis in 19 women. Of those 19, the task force estimated 17 or 18 would not die of breast cancer over 10 years, two would be treated for breast cancer that would not have caused problems, ie, overdiagnosis, and one to two would die of breast cancer.
Without screening, on the other hand, the model suggested that 983 of 1000 women aged 40-49 years would not be diagnosed with breast cancer, and 17 would be, 15 of whom would not die from breast cancer over 10 years (no overdiagnosis, no deaths prevented) and two would die.
It is important that family physicians provide their patients with this information to assist in shared decision making about screening, Thériault said.
Wilkinson concluded that screening programs that included women in their 40s were associated with a significantly higher breast cancer 10-year survival, without an increased rate of diagnosis. She suggested that the study findings can inform the screening guidelines for women aged 40-49 years.
The study was supported by the University of Ottawa’s department of family medicine.
Wilkinson, MD, is a consultant for Thrive Health. Thériault, MD, disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
The data call into question draft guidelines from the Canadian Task Force on Preventive Health Care, which suggest not systematically screening women in this age group with mammography.
Overdiagnosis Challenged
Given that some jurisdictions in Canada have organized screening programs and some do not, there was an opportunity to compare breast cancer 10-year net survival of women who lived in jurisdictions with and without such programs, explained family physician Anna N. Wilkinson, MD, Ottawa regional cancer primary care lead and associate professor at the University of Ottawa in Ontario, Canada.
“The question was [whether] we could use big cancer data to figure out what’s going on,” she told this news organization.
To investigate, Wilkinson and co-investigators reviewed data from the Canadian Cancer Registry linked to mortality information and assessed outcomes for women aged 40-49 and 50-59 years diagnosed with breast cancer from 2002 to 2007. They compared 10-year net survival estimates in jurisdictions with organized screening programs for those aged 40-49 years with the jurisdictions without them.
“Net survival is important because it’s a survival measure that looks at only the cancer in question,” Wilkinson explained.
Investigators determined breast cancer to be the primary cause of 10-year mortality in women aged 40-49 years diagnosed with the disease (90.7% of deaths).
Furthermore, the 10-year net survival in jurisdictions that screened these women (84.8%) was 1.9 percentage points higher than for jurisdictions that did not (82.9%).
The difference in 10-year net survival favoring jurisdictions that offered screening was significant for women aged 45-49 years (2.6 percentage points) but not for those aged 40-44 years (0.9 percentage points).
Given that 90% of the deaths in women in their 40s who had a breast cancer diagnosis were due to breast cancer, Wilkinson challenged the concept of women in their 40s being overdiagnosed with breast cancer, meaning that the cancers detected were indolent and did not require treatment nor result in death.
Earlier detection would generally mean finding disease at an earlier stage and the need for less invasive treatment, she noted. “And one of the biggest benefits [of screening women in their 40s] is that you have diagnosis at earlier stage disease, which means fewer intensive therapies, less time off work, less long-term morbidity, and less cost to our healthcare system.”
Modeling Shows Little Screening Benefit
The task force’s draft guidelines, released earlier this year, were based on evidence from 165 studies including randomized, controlled trials, observational studies, time-trend studies and modeling. They suggest not systematically screening women 40-49 with mammography who are not high risk.
Family physician Guylène Thériault, MD, chair of the task force and its breast cancer working group, and director of the Pedagogy Center at the Outaouais Campus, McGill University, Montreal, Quebec, Canada, explained that to come to that conclusion, the task force had assessed the impact of organized screening for women in Canada aged 40-49 years and calculated the impact of mammography for every 1000 women over 10 years.
The model suggested that screening would yield 368 false positives, leading to 55 biopsies, and then to a breast cancer diagnosis in 19 women. Of those 19, the task force estimated 17 or 18 would not die of breast cancer over 10 years, two would be treated for breast cancer that would not have caused problems, ie, overdiagnosis, and one to two would die of breast cancer.
Without screening, on the other hand, the model suggested that 983 of 1000 women aged 40-49 years would not be diagnosed with breast cancer, and 17 would be, 15 of whom would not die from breast cancer over 10 years (no overdiagnosis, no deaths prevented) and two would die.
It is important that family physicians provide their patients with this information to assist in shared decision making about screening, Thériault said.
Wilkinson concluded that screening programs that included women in their 40s were associated with a significantly higher breast cancer 10-year survival, without an increased rate of diagnosis. She suggested that the study findings can inform the screening guidelines for women aged 40-49 years.
The study was supported by the University of Ottawa’s department of family medicine.
Wilkinson, MD, is a consultant for Thrive Health. Thériault, MD, disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM FMF 2024
Vorasidenib for Certain IDH-Mutant Gliomas: Is It Worth It?
After years with limited treatment options, experts hailed vorasidenib “a promising breakthrough,” “a paradigm shift,” a “new hope,” and “probably the most important advance in the treatment of low-grade gliomas in the last decade.”
Promising results from vorasidenib’s pivotal INDIGO trial fueled petitions and patient advocacy circles to push for the drug’s approval. And, in August 2024, the Food and Drug Administration (FDA) approved vorasidenib for grade 2 astrocytomas or oligodendrogliomas with an IDH1 or IDH2 mutation.
But following the approval, some experts expressed concerns and doubts about the drug and the INDIGO trial, bringing a host of unanswered questions into sharper focus.
In an editorial, Stanislav Lazarev, MD, and Kunal K. Sindhu, MD, both radiation oncologists from Icahn School of Medicine at Mount Sinai, New York City, suggest that the FDA approval “might be premature given the high cost of this drug and lack of clear benefit over standard treatments.”
Another recent critique also pointed to the lack of clear evidence that vorasidenib is superior to the prevailing standard of care, despite the drug’s high cost. These authors noted that “patients want to live longer, and if not, at least live better,” but “based on the INDIGO study, it is impossible to say whether vorasidenib can provide either.”
Vorasidenib is now one of the most expensive cancer therapies, with an annual cost of nearly $500,000, but the INDIGO trial did not explore whether the drug led to improved overall survival or better quality of life. Among the trial’s design flaws, experts called out the use of progression-free survival as the primary outcome, instead of overall survival, and the use of an inappropriate comparator group.
INDIGO was a phase 3 trial that included 331 adult patients (median age, 40.5 years) with grade-2 IDH-mutant recurrent or residual glioma after surgery. To be eligible, patients had to be followed for at least 1 year, and up to 5 years, post surgery and had to be considered appropriate candidates for a watch-and-wait approach.
Participants were randomly assigned to receive either 40 mg of vorasidenib or a matching placebo orally, once daily, in continuous 28-day cycles until imaging-confirmed tumor disease progression or unacceptable toxicity, at which point crossover to vorasidenib from placebo was permitted. Over one third (n = 58) of patients in the placebo group crossed over and 90% of them (n = 52) received vorasidenib.
Median progression-free survival was significantly better in the vorasidenib group at 27.7 months vs 11.1 months in the placebo group (hazard ratio [HR], 0.39).
A key secondary endpoint — time to next intervention — was also significant; the likelihood of being alive and not receiving further treatment at 18 months was 85.6% in the vorasidenib group and 47.4% in the placebo group (HR, 0.26). This finding indicates that most patients receiving vorasidenib could delay chemoradiation for 18 months or longer.
Despite these impressive outcomes, some experts noted that using progression-free survival as the primary endpoint was a major flaw of the INDIGO trial because, currently, there is no evidence that progression-free survival is a reliable surrogate endpoint for overall survival in this setting.
The high rate of crossover to vorasidenib is another issue because it may limit a longer-term analysis of overall survival. If, for instance, overall survival is the same between the groups, it could signal that the drug is effective in both groups or, alternatively, that the drug has no effect on survival in either group.
“That is a legitimate concern,” Seema Nagpal, MD, a neuro-oncologist at Stanford University in California, and a site principal investigator for the INDIGO trial, said in an interview. “We don’t know that this drug changes overall survival, and I think we’re not going to get a super clean answer on that.”
Another major issue centers on the standard of care assigned to control patients in the INDIGO trial.
In the trial, vorasidenib was compared with placebo — an appropriate standard-of-care comparison for patients with low-risk gliomas. These patients often initially undergo watch-and-wait to delay chemoradiation. But Lazarev and Sindhu argue that the patients in INDIGO were really high risk, which means the control group should have received the standard of care for these patients: Chemoradiation following surgery.
This question about the appropriate standard of care stems from ongoing uncertainty about the distinction between high- and low-risk gliomas.
The classification for gliomas falls into either low risk or high risk for early disease progression. The RTOG 9802 criteria, often used for glioma risk stratification, defines low-risk patients as those younger than 40 years with gross total resection and high-risk patients as those aged 40 years or older with any extent of resection or those younger than 40 years with subtotal or biopsy resection.
But an evolving understanding of genetic anomalies that affect prognoses in this tumor type has muddied the current high- and low-risk distinctions.
“People haven’t totally figured out what high and low risk means,” Nagpal acknowledged.
This uncertainty has spilled over into the INDIGO trial.
While the trial excluded patients who had any features indicating high risk, such as brain stem involvement or neurocognitive deficits, the researchers also did not explicitly define patients as low risk. However, the inclusion criteria specified that patients had to be observed for at least 1 year after surgery and be considered appropriate for a watch-and-wait protocol, which does suggest patients were considered low risk, said Nagpal.
Still, some experts argue that the patients in INDIGO were not low risk.
Patients had residual or recurrent disease so “wouldn’t be classified as low risk,” said Sindhu in an interview. The standard of care for these patients is chemoradiation, Lazarev added.
“The definition of a phase 3 clinical trial is that you compare the novel intervention to the standard of care,” said Lazarev. “Level 1 evidence clearly shows that omitting chemoradiation leads to worse outcomes, with patients literally dying sooner. For the investigators to knowingly exclude this proven treatment raises serious ethical and methodological questions about the study’s design.”
In a recent opinion piece, Nagpal agreed that most patients selected for INDIGO would not have been considered low risk by many providers. All patients selected for INDIGO had postoperative residual/recurrent disease and many were older than 40 years.
But, Nagpal explained, the risk stratification of the INDIGO patients was still lower than what is commonly considered high risk. The patients had all been observed for a year or more already, “so by definition, the clinician treating them already decided they were not high risk,” she said.
In another recent opinion piece, oncologists suggested that, because patients in the INDIGO trial do not squarely fall into either category, instead representing a “grey area,” it’s time to create a new risk category.
“Perhaps the time has come to abandon the old binary risk stratification (“low risk” vs “high risk”), which still contains arbitrary elements (such as the age cutoff), proving impractical in real-world clinical decision-making, and to adopt a new one, also taking into account many emerging prognostic biomarkers,” the authors wrote.
Despite the uncertainty surrounding risk categories, the INDIGO authors justified their study design.
A watch-and-wait period for patients in the trial, which “represents the earliest clinical phase in tumorigenesis of IDH-mutant WHO grade 2 glioma,” is “an opportunity to detect a clear signal of antitumor activity for new therapies in placebo-controlled trials” and “postpone the use of radiation therapy and chemotherapy,” the authors explained.
Lazarev, however, questioned the premise that chemoradiation should be delayed.
Oncologists’ desire to delay chemoradiation for their patients reflects “a limited understanding of modern irradiation therapy,” Lazarev said. “Modern technology has improved dramatically. We’re more precise, our understanding about late side effects is better. So, the big picture is that the absolute risk of late neurocognitive affects that actually will affect patients’ quality of life, their ability to work, go to school, succeed on a personal or professional level is exceedingly low.”
Nagpal strongly disagreed.
“Please come to my clinic and ask an actual patient,” said Nagpal. “Once a radiation oncologist has irradiated the patient, they almost never seen them again. People who are on the medical side, who follow these patients from beginning to end, recognize that delaying radiation is a huge deal.”
Although vorasidenib isn’t a cure, Nagpal said, it is a less toxic way to delay radiation “because that is a real and disabling thing” for patients and is why neuro-oncologists are excited about alternative treatment options.
Another issue surrounding the vorasidenib approval lies in the FDA’s vague prescribing information. The prescribing information does not specify that patients should be followed for at least 1 year post surgery or that patients need to be lower risk. Prescribing physicians may, therefore, think vorasidenib is appropriate for any patient with a grade-2 IDH mutant glioma at any time and defer or not offer chemoradiation to high-risk patients.
Amid lingering questions about the INDIGO trial design and ongoing uncertainties about how to define and treat this patient population, experts remain divided on whether vorasidenib is worth it.
“If vorasidenib is truly transformative, it should be feasible to demonstrate its superiority over chemoradiotherapy,” Lazarev and Sindhu wrote. “For a drug with such a staggering price tag, an imperative should be placed on the investigators and manufacturer to provide clear evidence of efficacy, whether in terms of improved [overall survival] or quality of life, before vorasidenib is recommended for the treatment of IDH-mutant low-grade gliomas.”
The INDIGO trial was supported by Servier, the manufacturer of vorasidenib. Many of the study authors reported employment or support from the company. Nagpal reported consulting fees from Servier and AnHeart Therapeutics. Lazarev and Sindhu reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
After years with limited treatment options, experts hailed vorasidenib “a promising breakthrough,” “a paradigm shift,” a “new hope,” and “probably the most important advance in the treatment of low-grade gliomas in the last decade.”
Promising results from vorasidenib’s pivotal INDIGO trial fueled petitions and patient advocacy circles to push for the drug’s approval. And, in August 2024, the Food and Drug Administration (FDA) approved vorasidenib for grade 2 astrocytomas or oligodendrogliomas with an IDH1 or IDH2 mutation.
But following the approval, some experts expressed concerns and doubts about the drug and the INDIGO trial, bringing a host of unanswered questions into sharper focus.
In an editorial, Stanislav Lazarev, MD, and Kunal K. Sindhu, MD, both radiation oncologists from Icahn School of Medicine at Mount Sinai, New York City, suggest that the FDA approval “might be premature given the high cost of this drug and lack of clear benefit over standard treatments.”
Another recent critique also pointed to the lack of clear evidence that vorasidenib is superior to the prevailing standard of care, despite the drug’s high cost. These authors noted that “patients want to live longer, and if not, at least live better,” but “based on the INDIGO study, it is impossible to say whether vorasidenib can provide either.”
Vorasidenib is now one of the most expensive cancer therapies, with an annual cost of nearly $500,000, but the INDIGO trial did not explore whether the drug led to improved overall survival or better quality of life. Among the trial’s design flaws, experts called out the use of progression-free survival as the primary outcome, instead of overall survival, and the use of an inappropriate comparator group.
INDIGO was a phase 3 trial that included 331 adult patients (median age, 40.5 years) with grade-2 IDH-mutant recurrent or residual glioma after surgery. To be eligible, patients had to be followed for at least 1 year, and up to 5 years, post surgery and had to be considered appropriate candidates for a watch-and-wait approach.
Participants were randomly assigned to receive either 40 mg of vorasidenib or a matching placebo orally, once daily, in continuous 28-day cycles until imaging-confirmed tumor disease progression or unacceptable toxicity, at which point crossover to vorasidenib from placebo was permitted. Over one third (n = 58) of patients in the placebo group crossed over and 90% of them (n = 52) received vorasidenib.
Median progression-free survival was significantly better in the vorasidenib group at 27.7 months vs 11.1 months in the placebo group (hazard ratio [HR], 0.39).
A key secondary endpoint — time to next intervention — was also significant; the likelihood of being alive and not receiving further treatment at 18 months was 85.6% in the vorasidenib group and 47.4% in the placebo group (HR, 0.26). This finding indicates that most patients receiving vorasidenib could delay chemoradiation for 18 months or longer.
Despite these impressive outcomes, some experts noted that using progression-free survival as the primary endpoint was a major flaw of the INDIGO trial because, currently, there is no evidence that progression-free survival is a reliable surrogate endpoint for overall survival in this setting.
The high rate of crossover to vorasidenib is another issue because it may limit a longer-term analysis of overall survival. If, for instance, overall survival is the same between the groups, it could signal that the drug is effective in both groups or, alternatively, that the drug has no effect on survival in either group.
“That is a legitimate concern,” Seema Nagpal, MD, a neuro-oncologist at Stanford University in California, and a site principal investigator for the INDIGO trial, said in an interview. “We don’t know that this drug changes overall survival, and I think we’re not going to get a super clean answer on that.”
Another major issue centers on the standard of care assigned to control patients in the INDIGO trial.
In the trial, vorasidenib was compared with placebo — an appropriate standard-of-care comparison for patients with low-risk gliomas. These patients often initially undergo watch-and-wait to delay chemoradiation. But Lazarev and Sindhu argue that the patients in INDIGO were really high risk, which means the control group should have received the standard of care for these patients: Chemoradiation following surgery.
This question about the appropriate standard of care stems from ongoing uncertainty about the distinction between high- and low-risk gliomas.
The classification for gliomas falls into either low risk or high risk for early disease progression. The RTOG 9802 criteria, often used for glioma risk stratification, defines low-risk patients as those younger than 40 years with gross total resection and high-risk patients as those aged 40 years or older with any extent of resection or those younger than 40 years with subtotal or biopsy resection.
But an evolving understanding of genetic anomalies that affect prognoses in this tumor type has muddied the current high- and low-risk distinctions.
“People haven’t totally figured out what high and low risk means,” Nagpal acknowledged.
This uncertainty has spilled over into the INDIGO trial.
While the trial excluded patients who had any features indicating high risk, such as brain stem involvement or neurocognitive deficits, the researchers also did not explicitly define patients as low risk. However, the inclusion criteria specified that patients had to be observed for at least 1 year after surgery and be considered appropriate for a watch-and-wait protocol, which does suggest patients were considered low risk, said Nagpal.
Still, some experts argue that the patients in INDIGO were not low risk.
Patients had residual or recurrent disease so “wouldn’t be classified as low risk,” said Sindhu in an interview. The standard of care for these patients is chemoradiation, Lazarev added.
“The definition of a phase 3 clinical trial is that you compare the novel intervention to the standard of care,” said Lazarev. “Level 1 evidence clearly shows that omitting chemoradiation leads to worse outcomes, with patients literally dying sooner. For the investigators to knowingly exclude this proven treatment raises serious ethical and methodological questions about the study’s design.”
In a recent opinion piece, Nagpal agreed that most patients selected for INDIGO would not have been considered low risk by many providers. All patients selected for INDIGO had postoperative residual/recurrent disease and many were older than 40 years.
But, Nagpal explained, the risk stratification of the INDIGO patients was still lower than what is commonly considered high risk. The patients had all been observed for a year or more already, “so by definition, the clinician treating them already decided they were not high risk,” she said.
In another recent opinion piece, oncologists suggested that, because patients in the INDIGO trial do not squarely fall into either category, instead representing a “grey area,” it’s time to create a new risk category.
“Perhaps the time has come to abandon the old binary risk stratification (“low risk” vs “high risk”), which still contains arbitrary elements (such as the age cutoff), proving impractical in real-world clinical decision-making, and to adopt a new one, also taking into account many emerging prognostic biomarkers,” the authors wrote.
Despite the uncertainty surrounding risk categories, the INDIGO authors justified their study design.
A watch-and-wait period for patients in the trial, which “represents the earliest clinical phase in tumorigenesis of IDH-mutant WHO grade 2 glioma,” is “an opportunity to detect a clear signal of antitumor activity for new therapies in placebo-controlled trials” and “postpone the use of radiation therapy and chemotherapy,” the authors explained.
Lazarev, however, questioned the premise that chemoradiation should be delayed.
Oncologists’ desire to delay chemoradiation for their patients reflects “a limited understanding of modern irradiation therapy,” Lazarev said. “Modern technology has improved dramatically. We’re more precise, our understanding about late side effects is better. So, the big picture is that the absolute risk of late neurocognitive affects that actually will affect patients’ quality of life, their ability to work, go to school, succeed on a personal or professional level is exceedingly low.”
Nagpal strongly disagreed.
“Please come to my clinic and ask an actual patient,” said Nagpal. “Once a radiation oncologist has irradiated the patient, they almost never seen them again. People who are on the medical side, who follow these patients from beginning to end, recognize that delaying radiation is a huge deal.”
Although vorasidenib isn’t a cure, Nagpal said, it is a less toxic way to delay radiation “because that is a real and disabling thing” for patients and is why neuro-oncologists are excited about alternative treatment options.
Another issue surrounding the vorasidenib approval lies in the FDA’s vague prescribing information. The prescribing information does not specify that patients should be followed for at least 1 year post surgery or that patients need to be lower risk. Prescribing physicians may, therefore, think vorasidenib is appropriate for any patient with a grade-2 IDH mutant glioma at any time and defer or not offer chemoradiation to high-risk patients.
Amid lingering questions about the INDIGO trial design and ongoing uncertainties about how to define and treat this patient population, experts remain divided on whether vorasidenib is worth it.
“If vorasidenib is truly transformative, it should be feasible to demonstrate its superiority over chemoradiotherapy,” Lazarev and Sindhu wrote. “For a drug with such a staggering price tag, an imperative should be placed on the investigators and manufacturer to provide clear evidence of efficacy, whether in terms of improved [overall survival] or quality of life, before vorasidenib is recommended for the treatment of IDH-mutant low-grade gliomas.”
The INDIGO trial was supported by Servier, the manufacturer of vorasidenib. Many of the study authors reported employment or support from the company. Nagpal reported consulting fees from Servier and AnHeart Therapeutics. Lazarev and Sindhu reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
After years with limited treatment options, experts hailed vorasidenib “a promising breakthrough,” “a paradigm shift,” a “new hope,” and “probably the most important advance in the treatment of low-grade gliomas in the last decade.”
Promising results from vorasidenib’s pivotal INDIGO trial fueled petitions and patient advocacy circles to push for the drug’s approval. And, in August 2024, the Food and Drug Administration (FDA) approved vorasidenib for grade 2 astrocytomas or oligodendrogliomas with an IDH1 or IDH2 mutation.
But following the approval, some experts expressed concerns and doubts about the drug and the INDIGO trial, bringing a host of unanswered questions into sharper focus.
In an editorial, Stanislav Lazarev, MD, and Kunal K. Sindhu, MD, both radiation oncologists from Icahn School of Medicine at Mount Sinai, New York City, suggest that the FDA approval “might be premature given the high cost of this drug and lack of clear benefit over standard treatments.”
Another recent critique also pointed to the lack of clear evidence that vorasidenib is superior to the prevailing standard of care, despite the drug’s high cost. These authors noted that “patients want to live longer, and if not, at least live better,” but “based on the INDIGO study, it is impossible to say whether vorasidenib can provide either.”
Vorasidenib is now one of the most expensive cancer therapies, with an annual cost of nearly $500,000, but the INDIGO trial did not explore whether the drug led to improved overall survival or better quality of life. Among the trial’s design flaws, experts called out the use of progression-free survival as the primary outcome, instead of overall survival, and the use of an inappropriate comparator group.
INDIGO was a phase 3 trial that included 331 adult patients (median age, 40.5 years) with grade-2 IDH-mutant recurrent or residual glioma after surgery. To be eligible, patients had to be followed for at least 1 year, and up to 5 years, post surgery and had to be considered appropriate candidates for a watch-and-wait approach.
Participants were randomly assigned to receive either 40 mg of vorasidenib or a matching placebo orally, once daily, in continuous 28-day cycles until imaging-confirmed tumor disease progression or unacceptable toxicity, at which point crossover to vorasidenib from placebo was permitted. Over one third (n = 58) of patients in the placebo group crossed over and 90% of them (n = 52) received vorasidenib.
Median progression-free survival was significantly better in the vorasidenib group at 27.7 months vs 11.1 months in the placebo group (hazard ratio [HR], 0.39).
A key secondary endpoint — time to next intervention — was also significant; the likelihood of being alive and not receiving further treatment at 18 months was 85.6% in the vorasidenib group and 47.4% in the placebo group (HR, 0.26). This finding indicates that most patients receiving vorasidenib could delay chemoradiation for 18 months or longer.
Despite these impressive outcomes, some experts noted that using progression-free survival as the primary endpoint was a major flaw of the INDIGO trial because, currently, there is no evidence that progression-free survival is a reliable surrogate endpoint for overall survival in this setting.
The high rate of crossover to vorasidenib is another issue because it may limit a longer-term analysis of overall survival. If, for instance, overall survival is the same between the groups, it could signal that the drug is effective in both groups or, alternatively, that the drug has no effect on survival in either group.
“That is a legitimate concern,” Seema Nagpal, MD, a neuro-oncologist at Stanford University in California, and a site principal investigator for the INDIGO trial, said in an interview. “We don’t know that this drug changes overall survival, and I think we’re not going to get a super clean answer on that.”
Another major issue centers on the standard of care assigned to control patients in the INDIGO trial.
In the trial, vorasidenib was compared with placebo — an appropriate standard-of-care comparison for patients with low-risk gliomas. These patients often initially undergo watch-and-wait to delay chemoradiation. But Lazarev and Sindhu argue that the patients in INDIGO were really high risk, which means the control group should have received the standard of care for these patients: Chemoradiation following surgery.
This question about the appropriate standard of care stems from ongoing uncertainty about the distinction between high- and low-risk gliomas.
The classification for gliomas falls into either low risk or high risk for early disease progression. The RTOG 9802 criteria, often used for glioma risk stratification, defines low-risk patients as those younger than 40 years with gross total resection and high-risk patients as those aged 40 years or older with any extent of resection or those younger than 40 years with subtotal or biopsy resection.
But an evolving understanding of genetic anomalies that affect prognoses in this tumor type has muddied the current high- and low-risk distinctions.
“People haven’t totally figured out what high and low risk means,” Nagpal acknowledged.
This uncertainty has spilled over into the INDIGO trial.
While the trial excluded patients who had any features indicating high risk, such as brain stem involvement or neurocognitive deficits, the researchers also did not explicitly define patients as low risk. However, the inclusion criteria specified that patients had to be observed for at least 1 year after surgery and be considered appropriate for a watch-and-wait protocol, which does suggest patients were considered low risk, said Nagpal.
Still, some experts argue that the patients in INDIGO were not low risk.
Patients had residual or recurrent disease so “wouldn’t be classified as low risk,” said Sindhu in an interview. The standard of care for these patients is chemoradiation, Lazarev added.
“The definition of a phase 3 clinical trial is that you compare the novel intervention to the standard of care,” said Lazarev. “Level 1 evidence clearly shows that omitting chemoradiation leads to worse outcomes, with patients literally dying sooner. For the investigators to knowingly exclude this proven treatment raises serious ethical and methodological questions about the study’s design.”
In a recent opinion piece, Nagpal agreed that most patients selected for INDIGO would not have been considered low risk by many providers. All patients selected for INDIGO had postoperative residual/recurrent disease and many were older than 40 years.
But, Nagpal explained, the risk stratification of the INDIGO patients was still lower than what is commonly considered high risk. The patients had all been observed for a year or more already, “so by definition, the clinician treating them already decided they were not high risk,” she said.
In another recent opinion piece, oncologists suggested that, because patients in the INDIGO trial do not squarely fall into either category, instead representing a “grey area,” it’s time to create a new risk category.
“Perhaps the time has come to abandon the old binary risk stratification (“low risk” vs “high risk”), which still contains arbitrary elements (such as the age cutoff), proving impractical in real-world clinical decision-making, and to adopt a new one, also taking into account many emerging prognostic biomarkers,” the authors wrote.
Despite the uncertainty surrounding risk categories, the INDIGO authors justified their study design.
A watch-and-wait period for patients in the trial, which “represents the earliest clinical phase in tumorigenesis of IDH-mutant WHO grade 2 glioma,” is “an opportunity to detect a clear signal of antitumor activity for new therapies in placebo-controlled trials” and “postpone the use of radiation therapy and chemotherapy,” the authors explained.
Lazarev, however, questioned the premise that chemoradiation should be delayed.
Oncologists’ desire to delay chemoradiation for their patients reflects “a limited understanding of modern irradiation therapy,” Lazarev said. “Modern technology has improved dramatically. We’re more precise, our understanding about late side effects is better. So, the big picture is that the absolute risk of late neurocognitive affects that actually will affect patients’ quality of life, their ability to work, go to school, succeed on a personal or professional level is exceedingly low.”
Nagpal strongly disagreed.
“Please come to my clinic and ask an actual patient,” said Nagpal. “Once a radiation oncologist has irradiated the patient, they almost never seen them again. People who are on the medical side, who follow these patients from beginning to end, recognize that delaying radiation is a huge deal.”
Although vorasidenib isn’t a cure, Nagpal said, it is a less toxic way to delay radiation “because that is a real and disabling thing” for patients and is why neuro-oncologists are excited about alternative treatment options.
Another issue surrounding the vorasidenib approval lies in the FDA’s vague prescribing information. The prescribing information does not specify that patients should be followed for at least 1 year post surgery or that patients need to be lower risk. Prescribing physicians may, therefore, think vorasidenib is appropriate for any patient with a grade-2 IDH mutant glioma at any time and defer or not offer chemoradiation to high-risk patients.
Amid lingering questions about the INDIGO trial design and ongoing uncertainties about how to define and treat this patient population, experts remain divided on whether vorasidenib is worth it.
“If vorasidenib is truly transformative, it should be feasible to demonstrate its superiority over chemoradiotherapy,” Lazarev and Sindhu wrote. “For a drug with such a staggering price tag, an imperative should be placed on the investigators and manufacturer to provide clear evidence of efficacy, whether in terms of improved [overall survival] or quality of life, before vorasidenib is recommended for the treatment of IDH-mutant low-grade gliomas.”
The INDIGO trial was supported by Servier, the manufacturer of vorasidenib. Many of the study authors reported employment or support from the company. Nagpal reported consulting fees from Servier and AnHeart Therapeutics. Lazarev and Sindhu reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Inside the Patient-Oncologist Bond: Why It’s Often So Strong
Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.
“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”
That was 21 years ago. Today, her current cancer status is “no evidence of disease.”
Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.
In that time,
“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.
Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.
The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.
Gerber isn’t alone in calling out the depth of the oncologist-patient bond.
Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.
“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.
Connecting Through Stress
Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.
Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.
The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.
“I consider my patient’s battles to be my battles,” Khan wrote.
The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.
According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.
The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.
With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”
What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.
“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.
In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.
“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”
A ‘Special Relationship’
Ralph V. Boccia, MD, is often asked what he does.
The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.
“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”
Boccia thinks about one long-term patient who captures this bond.
Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.
Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.
Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.
“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”
Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.
Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.
Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.
More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.
“He has kept me alive,” said Pinson.
The Dying Patient
Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.
After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.
Several months later, Vyas was called for an inpatient consult. It was the same woman.
Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.
The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.
“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”
From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.
For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.
“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.
Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.
Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.
“Doc, I don’t want to die and my kids find me dead. What can we do about it?”
Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.
When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”
But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”
Khan had no relevant disclosures. Boccia and Vyas had no disclosures.
A version of this article appeared on Medscape.com.
Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.
“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”
That was 21 years ago. Today, her current cancer status is “no evidence of disease.”
Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.
In that time,
“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.
Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.
The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.
Gerber isn’t alone in calling out the depth of the oncologist-patient bond.
Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.
“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.
Connecting Through Stress
Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.
Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.
The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.
“I consider my patient’s battles to be my battles,” Khan wrote.
The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.
According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.
The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.
With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”
What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.
“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.
In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.
“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”
A ‘Special Relationship’
Ralph V. Boccia, MD, is often asked what he does.
The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.
“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”
Boccia thinks about one long-term patient who captures this bond.
Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.
Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.
Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.
“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”
Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.
Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.
Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.
More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.
“He has kept me alive,” said Pinson.
The Dying Patient
Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.
After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.
Several months later, Vyas was called for an inpatient consult. It was the same woman.
Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.
The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.
“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”
From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.
For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.
“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.
Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.
Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.
“Doc, I don’t want to die and my kids find me dead. What can we do about it?”
Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.
When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”
But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”
Khan had no relevant disclosures. Boccia and Vyas had no disclosures.
A version of this article appeared on Medscape.com.
Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.
“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”
That was 21 years ago. Today, her current cancer status is “no evidence of disease.”
Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.
In that time,
“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.
Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.
The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.
Gerber isn’t alone in calling out the depth of the oncologist-patient bond.
Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.
“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.
Connecting Through Stress
Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.
Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.
The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.
“I consider my patient’s battles to be my battles,” Khan wrote.
The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.
According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.
The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.
With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”
What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.
“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.
In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.
“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”
A ‘Special Relationship’
Ralph V. Boccia, MD, is often asked what he does.
The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.
“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”
Boccia thinks about one long-term patient who captures this bond.
Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.
Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.
Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.
“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”
Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.
Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.
Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.
More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.
“He has kept me alive,” said Pinson.
The Dying Patient
Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.
After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.
Several months later, Vyas was called for an inpatient consult. It was the same woman.
Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.
The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.
“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”
From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.
For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.
“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.
Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.
Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.
“Doc, I don’t want to die and my kids find me dead. What can we do about it?”
Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.
When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”
But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”
Khan had no relevant disclosures. Boccia and Vyas had no disclosures.
A version of this article appeared on Medscape.com.
Is 1-Week Radiotherapy Safe for Breast Cancer?
TOPLINE:
Most patients also reported that the reduced treatment time was a major benefit of the 1-week radiotherapy schedule.
METHODOLOGY:
- In March 2020, during the COVID-19 pandemic, international and national guidelines recommended adopting a 1-week ultrahypofractionated radiotherapy schedule for patients with node-negative breast cancer. Subsequently, a phase 3 trial demonstrated that a 1-week regimen of 26 Gy in five fractions led to similar breast cancer outcomes compared with a standard moderately hypofractionated regimen.
- In this study, researchers wanted to assess real world toxicities following ultrahypofractionated radiotherapy and enrolled 135 consecutive patients who received 1-week ultrahypofractionated adjuvant radiation of 26 Gy in five fractions from March to August 2020 at three centers in Ireland, with 33 patients (25%) receiving a sequential boost.
- Researchers recorded patient-reported outcomes on breast pain, swelling, firmness, and hypersensitivity at baseline, 3, 6, and 12 months. Virtual consultations without video occurred at baseline, 3 months, 6 months, and video consultations were offered at 1 year for a physician-led breast evaluation.
- Researchers assessed patient perspectives on this new schedule and telehealth workflows using questionnaires.
- Overall, 90% of patients completed the 1-year assessment plus another assessment. The primary endpoint was the worst toxicity reported at each time point.
TAKEAWAY:
- Overall, 76% of patients reported no or mild toxicities at 3 and 6 months, and 82% reported no or mild toxicities 12 months.
- At 1 year, 20 patients (17%) reported moderate toxicity, most commonly breast pain, and only two patients (2%) reported marked toxicities, including breast firmness and skin changes.
- Researchers found no difference in toxicities between patients who received only 26 Gy in five fractions and those who received an additional sequential boost.
- Most patients reported reduced treatment time (78.6%) and infection control (59%) as major benefits of the 1-week radiotherapy regimen. Patients also reported high satisfaction with the use of telehealth, with 97.3% feeling well-informed about their diagnosis, 88% feeling well-informed about treatment side effects, and 94% feeling supported by the medical team. However, only 27% agreed to video consultations for breast inspections at 1 year.
IN PRACTICE:
“Ultrahypofractionated whole breast radiotherapy leads to acceptable late toxicity rates at 1 year even when followed by a hypofractionated tumour bed boost,” the authors wrote. “Patient satisfaction with ultrahypofractionated treatment and virtual consultations without video was high.”
SOURCE:
The study, led by Jill Nicholson, MBBS, MRCP, FFFRRCSI, St Luke’s Radiation Oncology Network, St. Luke’s Hospital, Dublin, Ireland, was published online in Advances in Radiation Oncology.
LIMITATIONS:
The short follow-up period might not capture all late toxicities. Variability in patient-reported outcomes could affect consistency. The range in boost received (four to eight fractions) could have influenced patients’ experiences.
DISCLOSURES:
Nicholson received funding from the St. Luke’s Institute of Cancer Research, Dublin, Ireland. No other relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Most patients also reported that the reduced treatment time was a major benefit of the 1-week radiotherapy schedule.
METHODOLOGY:
- In March 2020, during the COVID-19 pandemic, international and national guidelines recommended adopting a 1-week ultrahypofractionated radiotherapy schedule for patients with node-negative breast cancer. Subsequently, a phase 3 trial demonstrated that a 1-week regimen of 26 Gy in five fractions led to similar breast cancer outcomes compared with a standard moderately hypofractionated regimen.
- In this study, researchers wanted to assess real world toxicities following ultrahypofractionated radiotherapy and enrolled 135 consecutive patients who received 1-week ultrahypofractionated adjuvant radiation of 26 Gy in five fractions from March to August 2020 at three centers in Ireland, with 33 patients (25%) receiving a sequential boost.
- Researchers recorded patient-reported outcomes on breast pain, swelling, firmness, and hypersensitivity at baseline, 3, 6, and 12 months. Virtual consultations without video occurred at baseline, 3 months, 6 months, and video consultations were offered at 1 year for a physician-led breast evaluation.
- Researchers assessed patient perspectives on this new schedule and telehealth workflows using questionnaires.
- Overall, 90% of patients completed the 1-year assessment plus another assessment. The primary endpoint was the worst toxicity reported at each time point.
TAKEAWAY:
- Overall, 76% of patients reported no or mild toxicities at 3 and 6 months, and 82% reported no or mild toxicities 12 months.
- At 1 year, 20 patients (17%) reported moderate toxicity, most commonly breast pain, and only two patients (2%) reported marked toxicities, including breast firmness and skin changes.
- Researchers found no difference in toxicities between patients who received only 26 Gy in five fractions and those who received an additional sequential boost.
- Most patients reported reduced treatment time (78.6%) and infection control (59%) as major benefits of the 1-week radiotherapy regimen. Patients also reported high satisfaction with the use of telehealth, with 97.3% feeling well-informed about their diagnosis, 88% feeling well-informed about treatment side effects, and 94% feeling supported by the medical team. However, only 27% agreed to video consultations for breast inspections at 1 year.
IN PRACTICE:
“Ultrahypofractionated whole breast radiotherapy leads to acceptable late toxicity rates at 1 year even when followed by a hypofractionated tumour bed boost,” the authors wrote. “Patient satisfaction with ultrahypofractionated treatment and virtual consultations without video was high.”
SOURCE:
The study, led by Jill Nicholson, MBBS, MRCP, FFFRRCSI, St Luke’s Radiation Oncology Network, St. Luke’s Hospital, Dublin, Ireland, was published online in Advances in Radiation Oncology.
LIMITATIONS:
The short follow-up period might not capture all late toxicities. Variability in patient-reported outcomes could affect consistency. The range in boost received (four to eight fractions) could have influenced patients’ experiences.
DISCLOSURES:
Nicholson received funding from the St. Luke’s Institute of Cancer Research, Dublin, Ireland. No other relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
Most patients also reported that the reduced treatment time was a major benefit of the 1-week radiotherapy schedule.
METHODOLOGY:
- In March 2020, during the COVID-19 pandemic, international and national guidelines recommended adopting a 1-week ultrahypofractionated radiotherapy schedule for patients with node-negative breast cancer. Subsequently, a phase 3 trial demonstrated that a 1-week regimen of 26 Gy in five fractions led to similar breast cancer outcomes compared with a standard moderately hypofractionated regimen.
- In this study, researchers wanted to assess real world toxicities following ultrahypofractionated radiotherapy and enrolled 135 consecutive patients who received 1-week ultrahypofractionated adjuvant radiation of 26 Gy in five fractions from March to August 2020 at three centers in Ireland, with 33 patients (25%) receiving a sequential boost.
- Researchers recorded patient-reported outcomes on breast pain, swelling, firmness, and hypersensitivity at baseline, 3, 6, and 12 months. Virtual consultations without video occurred at baseline, 3 months, 6 months, and video consultations were offered at 1 year for a physician-led breast evaluation.
- Researchers assessed patient perspectives on this new schedule and telehealth workflows using questionnaires.
- Overall, 90% of patients completed the 1-year assessment plus another assessment. The primary endpoint was the worst toxicity reported at each time point.
TAKEAWAY:
- Overall, 76% of patients reported no or mild toxicities at 3 and 6 months, and 82% reported no or mild toxicities 12 months.
- At 1 year, 20 patients (17%) reported moderate toxicity, most commonly breast pain, and only two patients (2%) reported marked toxicities, including breast firmness and skin changes.
- Researchers found no difference in toxicities between patients who received only 26 Gy in five fractions and those who received an additional sequential boost.
- Most patients reported reduced treatment time (78.6%) and infection control (59%) as major benefits of the 1-week radiotherapy regimen. Patients also reported high satisfaction with the use of telehealth, with 97.3% feeling well-informed about their diagnosis, 88% feeling well-informed about treatment side effects, and 94% feeling supported by the medical team. However, only 27% agreed to video consultations for breast inspections at 1 year.
IN PRACTICE:
“Ultrahypofractionated whole breast radiotherapy leads to acceptable late toxicity rates at 1 year even when followed by a hypofractionated tumour bed boost,” the authors wrote. “Patient satisfaction with ultrahypofractionated treatment and virtual consultations without video was high.”
SOURCE:
The study, led by Jill Nicholson, MBBS, MRCP, FFFRRCSI, St Luke’s Radiation Oncology Network, St. Luke’s Hospital, Dublin, Ireland, was published online in Advances in Radiation Oncology.
LIMITATIONS:
The short follow-up period might not capture all late toxicities. Variability in patient-reported outcomes could affect consistency. The range in boost received (four to eight fractions) could have influenced patients’ experiences.
DISCLOSURES:
Nicholson received funding from the St. Luke’s Institute of Cancer Research, Dublin, Ireland. No other relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.