AVAHO

TOPLINE:

Adding cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.

METHODOLOGY:

• Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
• The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
• Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m² loading dose, followed by 250 mg/m² weekly) or RT alone.
• The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
• Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.

TAKEAWAY:

• OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
• DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
• Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P < .0001), primarily affecting skin and mucosa, though late toxicity rates were similar (33.2% vs 29.0%; P = .3101).
• The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.

IN PRACTICE:

RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.

SOURCE:

This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online  in Journal of Clinical Oncology.

LIMITATIONS:

According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.

DISCLOSURES:

This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. Additional disclosures are noted in the original article.

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

TOPLINE:

Adding cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.

METHODOLOGY:

• Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
• The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
• Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m² loading dose, followed by 250 mg/m² weekly) or RT alone.
• The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
• Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.

TAKEAWAY:

• OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
• DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
• Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P < .0001), primarily affecting skin and mucosa, though late toxicity rates were similar (33.2% vs 29.0%; P = .3101).
• The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.

IN PRACTICE:

RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.

SOURCE:

This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online  in Journal of Clinical Oncology.

LIMITATIONS:

According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.

DISCLOSURES:

This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. Additional disclosures are noted in the original article.

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

TOPLINE:

Adding cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.

METHODOLOGY:

• Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
• The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
• Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m² loading dose, followed by 250 mg/m² weekly) or RT alone.
• The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
• Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.

TAKEAWAY:

• OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
• DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
• Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P < .0001), primarily affecting skin and mucosa, though late toxicity rates were similar (33.2% vs 29.0%; P = .3101).
• The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.

IN PRACTICE:

RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.

SOURCE:

This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online  in Journal of Clinical Oncology.

LIMITATIONS:

According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.

DISCLOSURES:

This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. Additional disclosures are noted in the original article.

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

Heavy menstrual bleeding is more than an inconvenience in adolescents: It often leads to significant medical complications, in addition to disruptions in quality of life. While measuring the true level of bleeding can be a challenge, hematologists say treatments are helpful and can be as simple — and surprising — as doses of aspirin.

About 90% of adolescents with heavy menstrual bleeding will have low ferritin, and 70% will develop anemia, said benign hematologist Juliana Perez Botero, MD, of the Mayo Clinic in Rochester, Minnesota, in a presentation at the American Society of Hematology (ASH) 2024 Annual Meeting. “This is an issue of big magnitude that has public health implications, but it’s also an issue of gender equality and social justice.”

 

Measuring Menstruation: What Counts as Heavy Bleeding?

According to hematologist Allison Wheeler, MD, of the University of Washington in Seattle, normal menstrual bleeding is defined as lasting for about 5 days with 30-50 mL of blood loss.

“Historically, heavy menstrual bleeding was defined as bleeding as > 7 days or > 80 mL of blood loss,” Wheeler said. “It’s pretty hard to measure those mL. So a more modern definition is increased menstrual blood loss that interferes with a female’s physical, social, emotional, or material quality of life.”

Measuring blood loss during menstruation isn’t simple. The alkaline hematin method, which measures blood in feminine hygiene products, is the “gold standard, but that’s all I’m going to say about that,” Wheeler said.

An alternative is the Pictorial Blood Loss Assessment Chart, a visual tool that patients can use to estimate blood loss, she said, although there have been questions about its accuracy. In addition, it only covers pads and tampons even though other products are now available.

Another option is the Adolescent Menstrual Bleeding Questionnaire. “It captures both how much patients are bleeding and a lot of quality-of-life aspects,” she said.

 

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Surprisingly, Can Be Effective Treatments

It seems counterintuitive that NSAIDs can be helpful in patients with heavy bleeding. “We don’t think about them because Cox inhibition ends up leading to decreases in thromboxane A2, which is going to increase bleeding,” Wheeler said. However, she said, the drugs also decrease prostaglandin within the endometrium, which can improve menstrual bleeding.

“In a meta-analysis, when NSAIDs were compared to placebo, there was decreased menstrual bleeding,” she said. “It was pretty similar to estrogen-progesterone formulations together. And when compared to antifibrinolytics, there was a little more menstrual bleeding with the NSAID use.”

Wheeler cautioned that “it’s important to optimize NSAID dosage. You really can’t use lower doses, and you can’t use sporadic doses.”

 

Other Options: Tranexamic Acid, Hormone Management

Tranexamic acid is the most common antifibrinolytic treatment for heavy bleeding, Wheeler said. “This is a lysine analog that’s going to inhibit the conversion from plasminogen to plasmin,” she said. “This is going to strengthen and stabilize blood clots that are already formed.”

Multiple clinical trials have studied the treatment in heavy menstrual bleeding, she said. “There’s no increased risk of venous or arterial thrombosis among participants in these clinical trials, but patients with a history of thrombosis were excluded from the majority of them. So we do need to keep that in mind.”

As for adverse effects, they’re mild and sporadic and include headaches and stomach upset, she said.

Another treatment option is estrogen and progesterone therapy using pill, patch, or vaginal ring, Wheeler said. The treatment leads to a “stable and thin very endometrium,” and typically takes 3-6 months to fully kick in. Studies have suggested the therapy can lead to 35%-80% reduction in menstrual blood loss, she said.

Keep in mind, Wheeler noted, “that there are many contraindications associated with estrogen use. Please take note of this, especially in consideration of discussions with patients shifting over to progesterone-only hormonal therapy” — another option to treat excess bleeding.

In most patients, she added, progesterone-only therapy “is going to result in irregular bleeding when you first start taking it. That irregular bleeding can last from up to 3-6 months. It’s something that’s really important to discuss with patients.”

She also noted that this therapy can be given to patients in forms that do not prevent pregnancy.

Botero had no disclosures. Wheeler reported relationships with Novo Nordisk, Bayer, BioMarin, Bioverativ, CSL Behring, Genentech, HEMA, Octapharma, Pfizer, Sanofi-Aventis, Shire North America, Spark, and Takeda.

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

Heavy menstrual bleeding is more than an inconvenience in adolescents: It often leads to significant medical complications, in addition to disruptions in quality of life. While measuring the true level of bleeding can be a challenge, hematologists say treatments are helpful and can be as simple — and surprising — as doses of aspirin.

About 90% of adolescents with heavy menstrual bleeding will have low ferritin, and 70% will develop anemia, said benign hematologist Juliana Perez Botero, MD, of the Mayo Clinic in Rochester, Minnesota, in a presentation at the American Society of Hematology (ASH) 2024 Annual Meeting. “This is an issue of big magnitude that has public health implications, but it’s also an issue of gender equality and social justice.”

 

Measuring Menstruation: What Counts as Heavy Bleeding?

According to hematologist Allison Wheeler, MD, of the University of Washington in Seattle, normal menstrual bleeding is defined as lasting for about 5 days with 30-50 mL of blood loss.

“Historically, heavy menstrual bleeding was defined as bleeding as > 7 days or > 80 mL of blood loss,” Wheeler said. “It’s pretty hard to measure those mL. So a more modern definition is increased menstrual blood loss that interferes with a female’s physical, social, emotional, or material quality of life.”

Measuring blood loss during menstruation isn’t simple. The alkaline hematin method, which measures blood in feminine hygiene products, is the “gold standard, but that’s all I’m going to say about that,” Wheeler said.

An alternative is the Pictorial Blood Loss Assessment Chart, a visual tool that patients can use to estimate blood loss, she said, although there have been questions about its accuracy. In addition, it only covers pads and tampons even though other products are now available.

Another option is the Adolescent Menstrual Bleeding Questionnaire. “It captures both how much patients are bleeding and a lot of quality-of-life aspects,” she said.

 

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Surprisingly, Can Be Effective Treatments

It seems counterintuitive that NSAIDs can be helpful in patients with heavy bleeding. “We don’t think about them because Cox inhibition ends up leading to decreases in thromboxane A2, which is going to increase bleeding,” Wheeler said. However, she said, the drugs also decrease prostaglandin within the endometrium, which can improve menstrual bleeding.

“In a meta-analysis, when NSAIDs were compared to placebo, there was decreased menstrual bleeding,” she said. “It was pretty similar to estrogen-progesterone formulations together. And when compared to antifibrinolytics, there was a little more menstrual bleeding with the NSAID use.”

Wheeler cautioned that “it’s important to optimize NSAID dosage. You really can’t use lower doses, and you can’t use sporadic doses.”

 

Other Options: Tranexamic Acid, Hormone Management

Tranexamic acid is the most common antifibrinolytic treatment for heavy bleeding, Wheeler said. “This is a lysine analog that’s going to inhibit the conversion from plasminogen to plasmin,” she said. “This is going to strengthen and stabilize blood clots that are already formed.”

Multiple clinical trials have studied the treatment in heavy menstrual bleeding, she said. “There’s no increased risk of venous or arterial thrombosis among participants in these clinical trials, but patients with a history of thrombosis were excluded from the majority of them. So we do need to keep that in mind.”

As for adverse effects, they’re mild and sporadic and include headaches and stomach upset, she said.

Another treatment option is estrogen and progesterone therapy using pill, patch, or vaginal ring, Wheeler said. The treatment leads to a “stable and thin very endometrium,” and typically takes 3-6 months to fully kick in. Studies have suggested the therapy can lead to 35%-80% reduction in menstrual blood loss, she said.

Keep in mind, Wheeler noted, “that there are many contraindications associated with estrogen use. Please take note of this, especially in consideration of discussions with patients shifting over to progesterone-only hormonal therapy” — another option to treat excess bleeding.

In most patients, she added, progesterone-only therapy “is going to result in irregular bleeding when you first start taking it. That irregular bleeding can last from up to 3-6 months. It’s something that’s really important to discuss with patients.”

She also noted that this therapy can be given to patients in forms that do not prevent pregnancy.

Botero had no disclosures. Wheeler reported relationships with Novo Nordisk, Bayer, BioMarin, Bioverativ, CSL Behring, Genentech, HEMA, Octapharma, Pfizer, Sanofi-Aventis, Shire North America, Spark, and Takeda.

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

Heavy menstrual bleeding is more than an inconvenience in adolescents: It often leads to significant medical complications, in addition to disruptions in quality of life. While measuring the true level of bleeding can be a challenge, hematologists say treatments are helpful and can be as simple — and surprising — as doses of aspirin.

About 90% of adolescents with heavy menstrual bleeding will have low ferritin, and 70% will develop anemia, said benign hematologist Juliana Perez Botero, MD, of the Mayo Clinic in Rochester, Minnesota, in a presentation at the American Society of Hematology (ASH) 2024 Annual Meeting. “This is an issue of big magnitude that has public health implications, but it’s also an issue of gender equality and social justice.”

 

Measuring Menstruation: What Counts as Heavy Bleeding?

According to hematologist Allison Wheeler, MD, of the University of Washington in Seattle, normal menstrual bleeding is defined as lasting for about 5 days with 30-50 mL of blood loss.

“Historically, heavy menstrual bleeding was defined as bleeding as > 7 days or > 80 mL of blood loss,” Wheeler said. “It’s pretty hard to measure those mL. So a more modern definition is increased menstrual blood loss that interferes with a female’s physical, social, emotional, or material quality of life.”

Measuring blood loss during menstruation isn’t simple. The alkaline hematin method, which measures blood in feminine hygiene products, is the “gold standard, but that’s all I’m going to say about that,” Wheeler said.

An alternative is the Pictorial Blood Loss Assessment Chart, a visual tool that patients can use to estimate blood loss, she said, although there have been questions about its accuracy. In addition, it only covers pads and tampons even though other products are now available.

Another option is the Adolescent Menstrual Bleeding Questionnaire. “It captures both how much patients are bleeding and a lot of quality-of-life aspects,” she said.

 

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Surprisingly, Can Be Effective Treatments

It seems counterintuitive that NSAIDs can be helpful in patients with heavy bleeding. “We don’t think about them because Cox inhibition ends up leading to decreases in thromboxane A2, which is going to increase bleeding,” Wheeler said. However, she said, the drugs also decrease prostaglandin within the endometrium, which can improve menstrual bleeding.

“In a meta-analysis, when NSAIDs were compared to placebo, there was decreased menstrual bleeding,” she said. “It was pretty similar to estrogen-progesterone formulations together. And when compared to antifibrinolytics, there was a little more menstrual bleeding with the NSAID use.”

Wheeler cautioned that “it’s important to optimize NSAID dosage. You really can’t use lower doses, and you can’t use sporadic doses.”

 

Other Options: Tranexamic Acid, Hormone Management

Tranexamic acid is the most common antifibrinolytic treatment for heavy bleeding, Wheeler said. “This is a lysine analog that’s going to inhibit the conversion from plasminogen to plasmin,” she said. “This is going to strengthen and stabilize blood clots that are already formed.”

Multiple clinical trials have studied the treatment in heavy menstrual bleeding, she said. “There’s no increased risk of venous or arterial thrombosis among participants in these clinical trials, but patients with a history of thrombosis were excluded from the majority of them. So we do need to keep that in mind.”

As for adverse effects, they’re mild and sporadic and include headaches and stomach upset, she said.

Another treatment option is estrogen and progesterone therapy using pill, patch, or vaginal ring, Wheeler said. The treatment leads to a “stable and thin very endometrium,” and typically takes 3-6 months to fully kick in. Studies have suggested the therapy can lead to 35%-80% reduction in menstrual blood loss, she said.

Keep in mind, Wheeler noted, “that there are many contraindications associated with estrogen use. Please take note of this, especially in consideration of discussions with patients shifting over to progesterone-only hormonal therapy” — another option to treat excess bleeding.

In most patients, she added, progesterone-only therapy “is going to result in irregular bleeding when you first start taking it. That irregular bleeding can last from up to 3-6 months. It’s something that’s really important to discuss with patients.”

She also noted that this therapy can be given to patients in forms that do not prevent pregnancy.

Botero had no disclosures. Wheeler reported relationships with Novo Nordisk, Bayer, BioMarin, Bioverativ, CSL Behring, Genentech, HEMA, Octapharma, Pfizer, Sanofi-Aventis, Shire North America, Spark, and Takeda.

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

TOPLINE:

A cross-sectional survey of patients preparing for their first radiation therapy consultation found that many patients worried about the physical effects of radiation therapy, including pain, memory loss, and nausea, and more than 60% said they were concerned about their ability to perform daily activities. Respondents reported a range of other worries, including the financial cost of treatment, transportation to treatment sessions, and the ability to continue working, as well as misconceptions about radiation therapy, such as concerns about emitting radiation to others.

METHODOLOGY:

• Toxicities from cancer therapies can significantly affect patients’ quality of life and may contribute to their apprehensions before starting a new treatment. Some studies have indicated that patients may have misconceptions about chemotherapy, but less is known about patients’ perceptions of radiation therapy.
• Researchers conducted a cross-sectional survey of patients presenting for initial radiation therapy consultation at a single academic institution and analyzed responses from 214 patients (52% men; 51% White individuals) with no prior radiation therapy experience.
• The patients completed a 30-question electronic survey about radiation therapy perceptions and fears or concerns prior to their initial radiation consultation.
• Cancer diagnoses spanned 18 disease sites, with hematologic malignancies (21%), breast cancer (18%), and lung cancer (15%) being the most common.

TAKEAWAY:

• Physical adverse effects were the top concern for patients. These included radiation-induced pain (67%), memory loss (62%), nausea/vomiting (60%), and skin reactions (58%).
• Patients expressed concerns about the impact radiation therapy would have on daily activities, with 62% reporting being moderately or very concerned about their ability to perform daily activities and 37% worried about their ability to continue working. Other concerns included the ability to exercise (over half of respondents), financial cost (36%), and transportation to treatment sessions (26%).
• Misconceptions among patients were also common, with 48% expressing concerns about emitting radiation to others and 45% worrying about excreting radioactive urine or stool.
• Patients had varied levels of prior understanding of radiation therapy. Half of patients reported a complete lack of knowledge about radiation therapy, and 35% said they had read or heard stories about bad adverse effects.

IN PRACTICE:

“Our study suggests that a survey administered prior to radiation oncology consultation can reveal patients’ primary concerns which could promote a more patient-centered discussion that addresses specific concerns and involves appropriate services to help the patient,” the authors wrote.

SOURCE:

This study, led by Jennifer Novak, MD, MS, Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California, was published online in Advances in Radiation Oncology.

LIMITATIONS:

Limitations included response bias and time constraints, which prevented many eligible patients from completing the survey. The single-institution design limits the generalizability of the findings. The survey results also showed a disproportionate focus on physical effects over the social impacts of radiation therapy, which could have limited the comprehensiveness of the findings.

DISCLOSURES:

The authors reported no specific funding for this work and no relevant competing financial interests or personal relationships that could have influenced the work.

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

TOPLINE:

A cross-sectional survey of patients preparing for their first radiation therapy consultation found that many patients worried about the physical effects of radiation therapy, including pain, memory loss, and nausea, and more than 60% said they were concerned about their ability to perform daily activities. Respondents reported a range of other worries, including the financial cost of treatment, transportation to treatment sessions, and the ability to continue working, as well as misconceptions about radiation therapy, such as concerns about emitting radiation to others.

METHODOLOGY:

• Toxicities from cancer therapies can significantly affect patients’ quality of life and may contribute to their apprehensions before starting a new treatment. Some studies have indicated that patients may have misconceptions about chemotherapy, but less is known about patients’ perceptions of radiation therapy.
• Researchers conducted a cross-sectional survey of patients presenting for initial radiation therapy consultation at a single academic institution and analyzed responses from 214 patients (52% men; 51% White individuals) with no prior radiation therapy experience.
• The patients completed a 30-question electronic survey about radiation therapy perceptions and fears or concerns prior to their initial radiation consultation.
• Cancer diagnoses spanned 18 disease sites, with hematologic malignancies (21%), breast cancer (18%), and lung cancer (15%) being the most common.

TAKEAWAY:

• Physical adverse effects were the top concern for patients. These included radiation-induced pain (67%), memory loss (62%), nausea/vomiting (60%), and skin reactions (58%).
• Patients expressed concerns about the impact radiation therapy would have on daily activities, with 62% reporting being moderately or very concerned about their ability to perform daily activities and 37% worried about their ability to continue working. Other concerns included the ability to exercise (over half of respondents), financial cost (36%), and transportation to treatment sessions (26%).
• Misconceptions among patients were also common, with 48% expressing concerns about emitting radiation to others and 45% worrying about excreting radioactive urine or stool.
• Patients had varied levels of prior understanding of radiation therapy. Half of patients reported a complete lack of knowledge about radiation therapy, and 35% said they had read or heard stories about bad adverse effects.

IN PRACTICE:

“Our study suggests that a survey administered prior to radiation oncology consultation can reveal patients’ primary concerns which could promote a more patient-centered discussion that addresses specific concerns and involves appropriate services to help the patient,” the authors wrote.

SOURCE:

This study, led by Jennifer Novak, MD, MS, Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California, was published online in Advances in Radiation Oncology.

LIMITATIONS:

Limitations included response bias and time constraints, which prevented many eligible patients from completing the survey. The single-institution design limits the generalizability of the findings. The survey results also showed a disproportionate focus on physical effects over the social impacts of radiation therapy, which could have limited the comprehensiveness of the findings.

DISCLOSURES:

The authors reported no specific funding for this work and no relevant competing financial interests or personal relationships that could have influenced the work.

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

TOPLINE:

A cross-sectional survey of patients preparing for their first radiation therapy consultation found that many patients worried about the physical effects of radiation therapy, including pain, memory loss, and nausea, and more than 60% said they were concerned about their ability to perform daily activities. Respondents reported a range of other worries, including the financial cost of treatment, transportation to treatment sessions, and the ability to continue working, as well as misconceptions about radiation therapy, such as concerns about emitting radiation to others.

METHODOLOGY:

• Toxicities from cancer therapies can significantly affect patients’ quality of life and may contribute to their apprehensions before starting a new treatment. Some studies have indicated that patients may have misconceptions about chemotherapy, but less is known about patients’ perceptions of radiation therapy.
• Researchers conducted a cross-sectional survey of patients presenting for initial radiation therapy consultation at a single academic institution and analyzed responses from 214 patients (52% men; 51% White individuals) with no prior radiation therapy experience.
• The patients completed a 30-question electronic survey about radiation therapy perceptions and fears or concerns prior to their initial radiation consultation.
• Cancer diagnoses spanned 18 disease sites, with hematologic malignancies (21%), breast cancer (18%), and lung cancer (15%) being the most common.

TAKEAWAY:

• Physical adverse effects were the top concern for patients. These included radiation-induced pain (67%), memory loss (62%), nausea/vomiting (60%), and skin reactions (58%).
• Patients expressed concerns about the impact radiation therapy would have on daily activities, with 62% reporting being moderately or very concerned about their ability to perform daily activities and 37% worried about their ability to continue working. Other concerns included the ability to exercise (over half of respondents), financial cost (36%), and transportation to treatment sessions (26%).
• Misconceptions among patients were also common, with 48% expressing concerns about emitting radiation to others and 45% worrying about excreting radioactive urine or stool.
• Patients had varied levels of prior understanding of radiation therapy. Half of patients reported a complete lack of knowledge about radiation therapy, and 35% said they had read or heard stories about bad adverse effects.

IN PRACTICE:

“Our study suggests that a survey administered prior to radiation oncology consultation can reveal patients’ primary concerns which could promote a more patient-centered discussion that addresses specific concerns and involves appropriate services to help the patient,” the authors wrote.

SOURCE:

This study, led by Jennifer Novak, MD, MS, Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California, was published online in Advances in Radiation Oncology.

LIMITATIONS:

Limitations included response bias and time constraints, which prevented many eligible patients from completing the survey. The single-institution design limits the generalizability of the findings. The survey results also showed a disproportionate focus on physical effects over the social impacts of radiation therapy, which could have limited the comprehensiveness of the findings.

DISCLOSURES:

The authors reported no specific funding for this work and no relevant competing financial interests or personal relationships that could have influenced the work.

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

Last year, Eric Singhi, MD, a thoracic medical oncologist at MD Anderson Cancer Center in Houston, noticed a shift in his team. The small band of four clinicians, once motivated and enthusiastic, were now withdrawn and distant.

“We had to take a break from clinic one day. We went out, got food and…acknowledged something was off,” Singhi recalled.

That something: Intense emotional exhaustion.

No thoracic oncology team has it easy. Lung cancer remains the leading cause of cancer deaths. But over the last 12 months Singhi’s team had taken on more and more cases in younger patients. Watching patients so close to their own age struggle and ultimately be consumed by this disease took its toll, Singhi said. And the toll was showing up in the lives of his colleagues.

Singhi’s team was suffering from compassion fatigue — the mental, physical, or emotional exhaustion brought on by prolonged exposure to the trauma of people in one’s care. Also referred to secondary trauma, compassion fatigue “leaves someone feeling numb, detached, or like they don’t have emotional resources to keep on giving,” Singhi said.

This fatigue is common among people who work in high-stress caretaking professions. Those involved in cancer care, who frequently find themselves navigating life and death conversations and experiences with patients, are particularly at risk, experts told this news organization.

“I think anyone in medical oncology or hematology who has practiced long enough will feel this,” said Alfred Lee, MD, PhD, burnout researcher and director of the hematology/oncology fellowship at Yale School of Medicine in New Haven, Connecticut. “It’s par for the course, even in training.”

Still, compassion fatigue can be hard to detect without help. Left unaddressed, compassion fatigue can undermine good patient care, even lead to burnout.

“I’ve absolutely treated people leaving the field who think they shouldn’t be a doctor anymore,” said Jennifer Bickel, MD, recently named MD Anderson’s inaugural vice president and chief wellness officer. Those are preventable losses the field can’t afford in a provider shortage, she said.

 

Recognizing the Signs

Compassion is an essential part of patient care as is empathy. Expressing compassion or feeling empathy toward patients can foster the doctor-patient bond and help both navigate challenging conversations and decisions.

“Compassion and being able to empathize are so important — it’s how you gain trust,” Singhi said. This is especially true for patients who may be underrepresented. “That’s how they become a partner in their care, how they agree to listen about a clinical trial or agree to adhere to their treatment plan,” Singhi noted.

But there’s a risk when clinicians start to give too much.

Overtime, repeated exposure to patients’ trauma can create a sense of heaviness and fatigue, and ultimately cause caregivers to detach, Lee said.

A case study of compassion fatigue, based on the experience of one oncologist, highlighted that the condition parallels posttraumatic stress disorder, aligning on three main symptoms: Feeling hyperarousal, notably hypervigilance or irritability, avoiding stressful situations, and reliving traumatic events.

The initial phases of compassion fatigue, however, can be subtle and easily dismissed. An oncologist may begin to feel a creeping sense of detachment — a divide slowly growing with their patients, a buzz of dissatisfaction on the job, unusual mood changes.

While it’s normal for healthcare workers to experience moments of irritability, dissatisfaction, exhaustion or avoidance, when these experiences become pervasive, compassion fatigue could be the culprit, according to Marra Ackerman, MD, a psychiatrist at NYU Langone Health in New York City.

Compassion fatigue is “a form of coping more than anything,” Ackerman explained. Most of the time, it’s not a conscious choice, she said. When a brain experiences repeated distressing inputs it can shift into self-protection mode. The tipping point is different for everyone, but eventually the brain tries to detach and distance itself from the stressor, Ackerman said. And, in oncology, that stressor is often very sick patients.

If not addressed, the emotional exhaustion can limit a doctor’s efficacy at work. Clinicians suffering from compassion fatigue may find themselves calling in sick more often, making more mistakes, avoiding very sick patients, or having panic attacks at work, said Ackerman.

Clinicians also might use food, drugs, or alcohol to feel better, or detach from their patients, Lee added. “We find if you detach, you can’t provide the care patients need,” he said.

When trying to identify the issue, it’s important to understand that compassion fatigue is not burnout. The two issues can look similar, sharing symptoms like emotional detachment or disillusionment, and may co-exist, but the phenomena stem from different root causes.

While compassion fatigue is rooted in emotions and isn’t necessarily tied to work, burnout is a product of work-related stress. It’s often caused by system-level problems that leave clinicians feeling their work has lost its meaning. Inefficient technology or excessive data entry, for instance, could be drivers of burnout for oncologists because these tasks can pull the doctor away from the meaningful work of treating patients.

 

What Can Be Done

Oncology comes with its own set of risks and traumas, but for a long time, doctors weren’t equipped or encouraged to see the constant life-or-death tension of the job as a risk factor to their well-being, said Bickel.

“It’s not something we are inherently taught to identify and it’s not something we can identify without time for self-reflection,” Bickel told this news organization. In fact, many people don’t see their own compassion fatigue until a colleague points it out or they’re already past it and have some distance.

Although common among oncology clinicians, compassion fatigue is not inevitable. Oncologists can learn strategies to help manage their exposures to suffering and stave off reverting to coping mechanisms that only perpetuate the problem.

The key, Bickel said, is creating environments where people can feel safe and share their vulnerabilities. Formal peer support check-ins are a good example because they normalize regular communication about day-to-day difficulties as they happen and create space to experience grief. In these groups, no one has to worry that they’re complaining, she said.

Formalized groups also serve as a training ground where staff can learn to be better listeners. Healthcare providers are more likely to reach out to peers because so few people outside their field can relate to the challenges, Bickel explained. That’s why Moffitt Cancer Center, where Bickel recently worked before moving to MD Anderson, offers trainings to help staff learn to listen more effectively. Thirty doctors, nurses and health professionals have received the training so far and serve as a point of contact for colleagues who might be struggling, Bickel said. They can offer their peers an empathic ear, without providing unsolicited advice or commentary.

NYU Langone has a similar offering, Ackerman said. Providers can reach out to fellow nurses or doctors who have more mental health training. The conversation isn’t recorded like an appointment with a therapist may be. It’s more like mentorship where doctors can be open about what they are facing and find some comradery from someone who understands, without fear of stigma.

Talking to colleagues or having debriefs with your care team is critical because it eliminates the isolation that allows compassion fatigue to fester, Lee said. “Reflecting on positive encounters can help inspire us to keep going. Reflecting on the negative can be therapeutic and help find that sense of balance that everyone needs to find.”

As for Singhi’s team, “lots has changed since we’ve become more open,” he said. The team talks about hard patients early and often. These discussions have helped team members keep the challenges at work from seeping into their home life.

Experts agree that the threshold for seeking out help and guidance should be low. Waiting for depression or more severe symptoms to set in is not the best point of intervention, Bickel said. As soon as an oncologist begins to acknowledge a shift in how they connect with patients and the job, that’s enough to reach out.

“It’s not about what you can handle, it’s about how can you thrive and find joy,” she said.

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

Last year, Eric Singhi, MD, a thoracic medical oncologist at MD Anderson Cancer Center in Houston, noticed a shift in his team. The small band of four clinicians, once motivated and enthusiastic, were now withdrawn and distant.

“We had to take a break from clinic one day. We went out, got food and…acknowledged something was off,” Singhi recalled.

That something: Intense emotional exhaustion.

No thoracic oncology team has it easy. Lung cancer remains the leading cause of cancer deaths. But over the last 12 months Singhi’s team had taken on more and more cases in younger patients. Watching patients so close to their own age struggle and ultimately be consumed by this disease took its toll, Singhi said. And the toll was showing up in the lives of his colleagues.

Singhi’s team was suffering from compassion fatigue — the mental, physical, or emotional exhaustion brought on by prolonged exposure to the trauma of people in one’s care. Also referred to secondary trauma, compassion fatigue “leaves someone feeling numb, detached, or like they don’t have emotional resources to keep on giving,” Singhi said.

This fatigue is common among people who work in high-stress caretaking professions. Those involved in cancer care, who frequently find themselves navigating life and death conversations and experiences with patients, are particularly at risk, experts told this news organization.

“I think anyone in medical oncology or hematology who has practiced long enough will feel this,” said Alfred Lee, MD, PhD, burnout researcher and director of the hematology/oncology fellowship at Yale School of Medicine in New Haven, Connecticut. “It’s par for the course, even in training.”

Still, compassion fatigue can be hard to detect without help. Left unaddressed, compassion fatigue can undermine good patient care, even lead to burnout.

“I’ve absolutely treated people leaving the field who think they shouldn’t be a doctor anymore,” said Jennifer Bickel, MD, recently named MD Anderson’s inaugural vice president and chief wellness officer. Those are preventable losses the field can’t afford in a provider shortage, she said.

 

Recognizing the Signs

Compassion is an essential part of patient care as is empathy. Expressing compassion or feeling empathy toward patients can foster the doctor-patient bond and help both navigate challenging conversations and decisions.

“Compassion and being able to empathize are so important — it’s how you gain trust,” Singhi said. This is especially true for patients who may be underrepresented. “That’s how they become a partner in their care, how they agree to listen about a clinical trial or agree to adhere to their treatment plan,” Singhi noted.

But there’s a risk when clinicians start to give too much.

Overtime, repeated exposure to patients’ trauma can create a sense of heaviness and fatigue, and ultimately cause caregivers to detach, Lee said.

A case study of compassion fatigue, based on the experience of one oncologist, highlighted that the condition parallels posttraumatic stress disorder, aligning on three main symptoms: Feeling hyperarousal, notably hypervigilance or irritability, avoiding stressful situations, and reliving traumatic events.

The initial phases of compassion fatigue, however, can be subtle and easily dismissed. An oncologist may begin to feel a creeping sense of detachment — a divide slowly growing with their patients, a buzz of dissatisfaction on the job, unusual mood changes.

While it’s normal for healthcare workers to experience moments of irritability, dissatisfaction, exhaustion or avoidance, when these experiences become pervasive, compassion fatigue could be the culprit, according to Marra Ackerman, MD, a psychiatrist at NYU Langone Health in New York City.

Compassion fatigue is “a form of coping more than anything,” Ackerman explained. Most of the time, it’s not a conscious choice, she said. When a brain experiences repeated distressing inputs it can shift into self-protection mode. The tipping point is different for everyone, but eventually the brain tries to detach and distance itself from the stressor, Ackerman said. And, in oncology, that stressor is often very sick patients.

If not addressed, the emotional exhaustion can limit a doctor’s efficacy at work. Clinicians suffering from compassion fatigue may find themselves calling in sick more often, making more mistakes, avoiding very sick patients, or having panic attacks at work, said Ackerman.

Clinicians also might use food, drugs, or alcohol to feel better, or detach from their patients, Lee added. “We find if you detach, you can’t provide the care patients need,” he said.

When trying to identify the issue, it’s important to understand that compassion fatigue is not burnout. The two issues can look similar, sharing symptoms like emotional detachment or disillusionment, and may co-exist, but the phenomena stem from different root causes.

While compassion fatigue is rooted in emotions and isn’t necessarily tied to work, burnout is a product of work-related stress. It’s often caused by system-level problems that leave clinicians feeling their work has lost its meaning. Inefficient technology or excessive data entry, for instance, could be drivers of burnout for oncologists because these tasks can pull the doctor away from the meaningful work of treating patients.

 

What Can Be Done

Oncology comes with its own set of risks and traumas, but for a long time, doctors weren’t equipped or encouraged to see the constant life-or-death tension of the job as a risk factor to their well-being, said Bickel.

“It’s not something we are inherently taught to identify and it’s not something we can identify without time for self-reflection,” Bickel told this news organization. In fact, many people don’t see their own compassion fatigue until a colleague points it out or they’re already past it and have some distance.

Although common among oncology clinicians, compassion fatigue is not inevitable. Oncologists can learn strategies to help manage their exposures to suffering and stave off reverting to coping mechanisms that only perpetuate the problem.

The key, Bickel said, is creating environments where people can feel safe and share their vulnerabilities. Formal peer support check-ins are a good example because they normalize regular communication about day-to-day difficulties as they happen and create space to experience grief. In these groups, no one has to worry that they’re complaining, she said.

Formalized groups also serve as a training ground where staff can learn to be better listeners. Healthcare providers are more likely to reach out to peers because so few people outside their field can relate to the challenges, Bickel explained. That’s why Moffitt Cancer Center, where Bickel recently worked before moving to MD Anderson, offers trainings to help staff learn to listen more effectively. Thirty doctors, nurses and health professionals have received the training so far and serve as a point of contact for colleagues who might be struggling, Bickel said. They can offer their peers an empathic ear, without providing unsolicited advice or commentary.

NYU Langone has a similar offering, Ackerman said. Providers can reach out to fellow nurses or doctors who have more mental health training. The conversation isn’t recorded like an appointment with a therapist may be. It’s more like mentorship where doctors can be open about what they are facing and find some comradery from someone who understands, without fear of stigma.

Talking to colleagues or having debriefs with your care team is critical because it eliminates the isolation that allows compassion fatigue to fester, Lee said. “Reflecting on positive encounters can help inspire us to keep going. Reflecting on the negative can be therapeutic and help find that sense of balance that everyone needs to find.”

As for Singhi’s team, “lots has changed since we’ve become more open,” he said. The team talks about hard patients early and often. These discussions have helped team members keep the challenges at work from seeping into their home life.

Experts agree that the threshold for seeking out help and guidance should be low. Waiting for depression or more severe symptoms to set in is not the best point of intervention, Bickel said. As soon as an oncologist begins to acknowledge a shift in how they connect with patients and the job, that’s enough to reach out.

“It’s not about what you can handle, it’s about how can you thrive and find joy,” she said.

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

Last year, Eric Singhi, MD, a thoracic medical oncologist at MD Anderson Cancer Center in Houston, noticed a shift in his team. The small band of four clinicians, once motivated and enthusiastic, were now withdrawn and distant.

“We had to take a break from clinic one day. We went out, got food and…acknowledged something was off,” Singhi recalled.

That something: Intense emotional exhaustion.

No thoracic oncology team has it easy. Lung cancer remains the leading cause of cancer deaths. But over the last 12 months Singhi’s team had taken on more and more cases in younger patients. Watching patients so close to their own age struggle and ultimately be consumed by this disease took its toll, Singhi said. And the toll was showing up in the lives of his colleagues.

Singhi’s team was suffering from compassion fatigue — the mental, physical, or emotional exhaustion brought on by prolonged exposure to the trauma of people in one’s care. Also referred to secondary trauma, compassion fatigue “leaves someone feeling numb, detached, or like they don’t have emotional resources to keep on giving,” Singhi said.

This fatigue is common among people who work in high-stress caretaking professions. Those involved in cancer care, who frequently find themselves navigating life and death conversations and experiences with patients, are particularly at risk, experts told this news organization.

“I think anyone in medical oncology or hematology who has practiced long enough will feel this,” said Alfred Lee, MD, PhD, burnout researcher and director of the hematology/oncology fellowship at Yale School of Medicine in New Haven, Connecticut. “It’s par for the course, even in training.”

Still, compassion fatigue can be hard to detect without help. Left unaddressed, compassion fatigue can undermine good patient care, even lead to burnout.

“I’ve absolutely treated people leaving the field who think they shouldn’t be a doctor anymore,” said Jennifer Bickel, MD, recently named MD Anderson’s inaugural vice president and chief wellness officer. Those are preventable losses the field can’t afford in a provider shortage, she said.

 

Recognizing the Signs

Compassion is an essential part of patient care as is empathy. Expressing compassion or feeling empathy toward patients can foster the doctor-patient bond and help both navigate challenging conversations and decisions.

“Compassion and being able to empathize are so important — it’s how you gain trust,” Singhi said. This is especially true for patients who may be underrepresented. “That’s how they become a partner in their care, how they agree to listen about a clinical trial or agree to adhere to their treatment plan,” Singhi noted.

But there’s a risk when clinicians start to give too much.

Overtime, repeated exposure to patients’ trauma can create a sense of heaviness and fatigue, and ultimately cause caregivers to detach, Lee said.

A case study of compassion fatigue, based on the experience of one oncologist, highlighted that the condition parallels posttraumatic stress disorder, aligning on three main symptoms: Feeling hyperarousal, notably hypervigilance or irritability, avoiding stressful situations, and reliving traumatic events.

The initial phases of compassion fatigue, however, can be subtle and easily dismissed. An oncologist may begin to feel a creeping sense of detachment — a divide slowly growing with their patients, a buzz of dissatisfaction on the job, unusual mood changes.

While it’s normal for healthcare workers to experience moments of irritability, dissatisfaction, exhaustion or avoidance, when these experiences become pervasive, compassion fatigue could be the culprit, according to Marra Ackerman, MD, a psychiatrist at NYU Langone Health in New York City.

Compassion fatigue is “a form of coping more than anything,” Ackerman explained. Most of the time, it’s not a conscious choice, she said. When a brain experiences repeated distressing inputs it can shift into self-protection mode. The tipping point is different for everyone, but eventually the brain tries to detach and distance itself from the stressor, Ackerman said. And, in oncology, that stressor is often very sick patients.

If not addressed, the emotional exhaustion can limit a doctor’s efficacy at work. Clinicians suffering from compassion fatigue may find themselves calling in sick more often, making more mistakes, avoiding very sick patients, or having panic attacks at work, said Ackerman.

Clinicians also might use food, drugs, or alcohol to feel better, or detach from their patients, Lee added. “We find if you detach, you can’t provide the care patients need,” he said.

When trying to identify the issue, it’s important to understand that compassion fatigue is not burnout. The two issues can look similar, sharing symptoms like emotional detachment or disillusionment, and may co-exist, but the phenomena stem from different root causes.

While compassion fatigue is rooted in emotions and isn’t necessarily tied to work, burnout is a product of work-related stress. It’s often caused by system-level problems that leave clinicians feeling their work has lost its meaning. Inefficient technology or excessive data entry, for instance, could be drivers of burnout for oncologists because these tasks can pull the doctor away from the meaningful work of treating patients.

 

What Can Be Done

Oncology comes with its own set of risks and traumas, but for a long time, doctors weren’t equipped or encouraged to see the constant life-or-death tension of the job as a risk factor to their well-being, said Bickel.

“It’s not something we are inherently taught to identify and it’s not something we can identify without time for self-reflection,” Bickel told this news organization. In fact, many people don’t see their own compassion fatigue until a colleague points it out or they’re already past it and have some distance.

Although common among oncology clinicians, compassion fatigue is not inevitable. Oncologists can learn strategies to help manage their exposures to suffering and stave off reverting to coping mechanisms that only perpetuate the problem.

The key, Bickel said, is creating environments where people can feel safe and share their vulnerabilities. Formal peer support check-ins are a good example because they normalize regular communication about day-to-day difficulties as they happen and create space to experience grief. In these groups, no one has to worry that they’re complaining, she said.

Formalized groups also serve as a training ground where staff can learn to be better listeners. Healthcare providers are more likely to reach out to peers because so few people outside their field can relate to the challenges, Bickel explained. That’s why Moffitt Cancer Center, where Bickel recently worked before moving to MD Anderson, offers trainings to help staff learn to listen more effectively. Thirty doctors, nurses and health professionals have received the training so far and serve as a point of contact for colleagues who might be struggling, Bickel said. They can offer their peers an empathic ear, without providing unsolicited advice or commentary.

NYU Langone has a similar offering, Ackerman said. Providers can reach out to fellow nurses or doctors who have more mental health training. The conversation isn’t recorded like an appointment with a therapist may be. It’s more like mentorship where doctors can be open about what they are facing and find some comradery from someone who understands, without fear of stigma.

Talking to colleagues or having debriefs with your care team is critical because it eliminates the isolation that allows compassion fatigue to fester, Lee said. “Reflecting on positive encounters can help inspire us to keep going. Reflecting on the negative can be therapeutic and help find that sense of balance that everyone needs to find.”

As for Singhi’s team, “lots has changed since we’ve become more open,” he said. The team talks about hard patients early and often. These discussions have helped team members keep the challenges at work from seeping into their home life.

Experts agree that the threshold for seeking out help and guidance should be low. Waiting for depression or more severe symptoms to set in is not the best point of intervention, Bickel said. As soon as an oncologist begins to acknowledge a shift in how they connect with patients and the job, that’s enough to reach out.

“It’s not about what you can handle, it’s about how can you thrive and find joy,” she said.

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

TOPLINE: A small study of veterans found that high-intensity focused ultrasound (HIFU) demonstrated similar oncologic outcomes when compared to standard treatments for localized prostate cancer, while maintaining erectile and urinary function. 

METHODOLOGY: 

•      A retrospective analysis at the Michael E. DeBakey Veterans Affairs Medical Center in Houston between 2018 and 2022, with data acquired from electronic health record.
•      A total of 43 veterans were included in the analysis; 31 patients (72%) receiving primary treatment and 12 patients (28%) receiving salvage therapy.
•      Patient risk stratification was performed using prostate specific antigen (PSA), Gleason Score, and clinical stage based on National Comprehensive Cancer Network and D'Amico criteria.
•      Follow-up assessments included serial PSA measurements at 3, 6, 12, 18, and 24 months, with functional outcomes evaluated through Sexual Health Inventory for Men and American Urological Association Symptom Score questionnaires.

TAKEAWAY:

•       The 31 patients in the primary treatment group had a median PSA nadir of 0.16, while the 12 patients in the salvage therapy group had a median PSA nadir of 0.12, with median follow-up periods of 23 and 25 months, respectively.
•       Local recurrence rates were comparable between groups, occurring in 5 patients (16%) in the primary group and 2 (17%) in the salvage group.
•       Sexual Health Inventory for Men scores and American Urological Association Symptom Score showed no statistically significant differences before and after HIFU therapy in both groups (P = .35). > .05).
•       Short- and intermediate-term results demonstrated HIFU's effectiveness in maintaining potency and urinary function while providing adequate oncological control for both primary and salvage therapies.
•      Two patients (7%) from the primary treatment group experienced 30-day complications, including one case of epididymo-orchitis and 1 case of urethral stricture.
•      Three patients (25%) from the salvage treatment group experienced 30-day complications, including one bladder neck contracture.

IN PRACTICE: "The application of HIFU in a veteran population is of particular interest due to the unique medical challenges this group faces. Veterans often present with complex medical conditions and a higher comorbidity burden compared to the general population, as indicated by a median Charleson Comorbidity Index of 7 in our primary HIFU group," wrote the authors of the study. 

SOURCE: The study was led by Sagar Patel and Ali Antar, Operative Care Line, Urology Section, Michael E. DeBakey Veteran Affairs Medical Center in Houston. It was published online in Life.

 LIMITATIONS: The study's relatively short median follow-up period of 23-25 months limits the assessment of long-term oncological outcomes in prostate cancer. The sample size, while substantial for an initial series, remains modest, particularly for the salvage therapy group. According to the authors, larger multi-center studies with longer follow-up periods will be necessary to confirm and extend these findings, especially for establishing the durability of oncological control and functional preservation. 

DISCLOSURES: The study received no external funding. The research was conducted in accordance with the Declaration of Helsinki and received approval from the Institutional Review Board in February 2024. Support was obtained from the Prostate Cancer Foundation-VALOR Challenge Program. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication

TOPLINE: A small study of veterans found that high-intensity focused ultrasound (HIFU) demonstrated similar oncologic outcomes when compared to standard treatments for localized prostate cancer, while maintaining erectile and urinary function. 

METHODOLOGY: 

•      A retrospective analysis at the Michael E. DeBakey Veterans Affairs Medical Center in Houston between 2018 and 2022, with data acquired from electronic health record.
•      A total of 43 veterans were included in the analysis; 31 patients (72%) receiving primary treatment and 12 patients (28%) receiving salvage therapy.
•      Patient risk stratification was performed using prostate specific antigen (PSA), Gleason Score, and clinical stage based on National Comprehensive Cancer Network and D'Amico criteria.
•      Follow-up assessments included serial PSA measurements at 3, 6, 12, 18, and 24 months, with functional outcomes evaluated through Sexual Health Inventory for Men and American Urological Association Symptom Score questionnaires.

TAKEAWAY:

•       The 31 patients in the primary treatment group had a median PSA nadir of 0.16, while the 12 patients in the salvage therapy group had a median PSA nadir of 0.12, with median follow-up periods of 23 and 25 months, respectively.
•       Local recurrence rates were comparable between groups, occurring in 5 patients (16%) in the primary group and 2 (17%) in the salvage group.
•       Sexual Health Inventory for Men scores and American Urological Association Symptom Score showed no statistically significant differences before and after HIFU therapy in both groups (P = .35). > .05).
•       Short- and intermediate-term results demonstrated HIFU's effectiveness in maintaining potency and urinary function while providing adequate oncological control for both primary and salvage therapies.
•      Two patients (7%) from the primary treatment group experienced 30-day complications, including one case of epididymo-orchitis and 1 case of urethral stricture.
•      Three patients (25%) from the salvage treatment group experienced 30-day complications, including one bladder neck contracture.

IN PRACTICE: "The application of HIFU in a veteran population is of particular interest due to the unique medical challenges this group faces. Veterans often present with complex medical conditions and a higher comorbidity burden compared to the general population, as indicated by a median Charleson Comorbidity Index of 7 in our primary HIFU group," wrote the authors of the study. 

SOURCE: The study was led by Sagar Patel and Ali Antar, Operative Care Line, Urology Section, Michael E. DeBakey Veteran Affairs Medical Center in Houston. It was published online in Life.

 LIMITATIONS: The study's relatively short median follow-up period of 23-25 months limits the assessment of long-term oncological outcomes in prostate cancer. The sample size, while substantial for an initial series, remains modest, particularly for the salvage therapy group. According to the authors, larger multi-center studies with longer follow-up periods will be necessary to confirm and extend these findings, especially for establishing the durability of oncological control and functional preservation. 

DISCLOSURES: The study received no external funding. The research was conducted in accordance with the Declaration of Helsinki and received approval from the Institutional Review Board in February 2024. Support was obtained from the Prostate Cancer Foundation-VALOR Challenge Program. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication

TOPLINE: A small study of veterans found that high-intensity focused ultrasound (HIFU) demonstrated similar oncologic outcomes when compared to standard treatments for localized prostate cancer, while maintaining erectile and urinary function. 

METHODOLOGY: 

•      A retrospective analysis at the Michael E. DeBakey Veterans Affairs Medical Center in Houston between 2018 and 2022, with data acquired from electronic health record.
•      A total of 43 veterans were included in the analysis; 31 patients (72%) receiving primary treatment and 12 patients (28%) receiving salvage therapy.
•      Patient risk stratification was performed using prostate specific antigen (PSA), Gleason Score, and clinical stage based on National Comprehensive Cancer Network and D'Amico criteria.
•      Follow-up assessments included serial PSA measurements at 3, 6, 12, 18, and 24 months, with functional outcomes evaluated through Sexual Health Inventory for Men and American Urological Association Symptom Score questionnaires.

TAKEAWAY:

•       The 31 patients in the primary treatment group had a median PSA nadir of 0.16, while the 12 patients in the salvage therapy group had a median PSA nadir of 0.12, with median follow-up periods of 23 and 25 months, respectively.
•       Local recurrence rates were comparable between groups, occurring in 5 patients (16%) in the primary group and 2 (17%) in the salvage group.
•       Sexual Health Inventory for Men scores and American Urological Association Symptom Score showed no statistically significant differences before and after HIFU therapy in both groups (P = .35). > .05).
•       Short- and intermediate-term results demonstrated HIFU's effectiveness in maintaining potency and urinary function while providing adequate oncological control for both primary and salvage therapies.
•      Two patients (7%) from the primary treatment group experienced 30-day complications, including one case of epididymo-orchitis and 1 case of urethral stricture.
•      Three patients (25%) from the salvage treatment group experienced 30-day complications, including one bladder neck contracture.

IN PRACTICE: "The application of HIFU in a veteran population is of particular interest due to the unique medical challenges this group faces. Veterans often present with complex medical conditions and a higher comorbidity burden compared to the general population, as indicated by a median Charleson Comorbidity Index of 7 in our primary HIFU group," wrote the authors of the study. 

SOURCE: The study was led by Sagar Patel and Ali Antar, Operative Care Line, Urology Section, Michael E. DeBakey Veteran Affairs Medical Center in Houston. It was published online in Life.

 LIMITATIONS: The study's relatively short median follow-up period of 23-25 months limits the assessment of long-term oncological outcomes in prostate cancer. The sample size, while substantial for an initial series, remains modest, particularly for the salvage therapy group. According to the authors, larger multi-center studies with longer follow-up periods will be necessary to confirm and extend these findings, especially for establishing the durability of oncological control and functional preservation. 

DISCLOSURES: The study received no external funding. The research was conducted in accordance with the Declaration of Helsinki and received approval from the Institutional Review Board in February 2024. Support was obtained from the Prostate Cancer Foundation-VALOR Challenge Program. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication

Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

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

Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

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

Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

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

The US Department of Veterans Affairs (VA) has outlined > 300,000 exemptions to the federal hiring freeze to fill essential benefits and health positions. The exempted positions are primarily medical support staff. While the exemptions include pharmacists, physicians and nurses were not included. The day after taking office for the second time, President Trump signed an Executive Order implementing a “freeze on the hiring of Federal civilian employees, to be applied throughout the executive branch” but left many of the details to individual agencies.

Set to last 90 days, the hiring freeze forced Federal agencies to develop plans to reduce the size of their workforces through efficiencies and attrition, Trump said. These agencies would also not be able to hire contractors.

Three days later, however, the VA responded “Following successful implementation of President Trump’s federal hiring freeze, the Department of Veterans Affairs announced several exemptions to the policy. These exemptions clarify the department’s ability to continue filling essential positions that provide health care and other vital services to Veterans and VA beneficiaries.”

This allowed > 304,000 jobs to be exempt from the freeze. Almost 92% of the VA’s 450,000 employees work in health care and health administration and support services. Most of the exemptions involve support staff. No physicians, mental health professionals or nursing positions are on the list. However, it does include 12,622 pharmacists and 5,975 pharmacy technicians. 

The VA worked in accordance with the White House and Office of Personnel Management to develop the updated guidance, Acting Veterans Affairs Secretary Todd Hunter said. In a Jan. 21 memo, Hunter wrote: "Positions critical to delivering care to veterans in the Veteran[s] Health Administration ... are exempted under the category of public safety.”

According to Hunter's memo, no other vacancies that existed as of midday Monday will be filled. Candidates who received job offers before noon on Jan. 20 and have a start date on or before Feb. 8 will be onboarded, while those with a start date after Feb. 8—or one that is undetermined—will have their offers rescinded.

The first Trump Administration began the same way in 2017, initiating a freeze on Federal hiring and receiving a similar response from the VA. In 2017, the hiring of doctors and nurses continued while that freeze was in effect, but onboarding of new support and administrative staff was not. Then-Secretary of Veterans Affairs Dr. David J. Shulkin said, “VA is committed to serving veterans, but at the same time improving efficiency and reducing bureaucracy.” 

The current Executive Order states it “shall not adversely impact veterans’ benefits and does not apply to positions related to public safety” (or military personnel, immigration enforcement, and national security). It also says it does not adversely impact the provision of Social Security, Medicare, or Veterans’ benefits. 

“Under President Trump’s leadership, VA will always do what is necessary to provide America’s Veterans with the benefits and services they have earned. The targeted hiring-freeze exemptions announced today underscore that fact,” said VA Director of Media Affairs Morgan Ackley.  

Some in Congress feel the VA should be doing more, though, and are pushing for an exemption of all VA employees. On Friday, Senate Veterans’ Affairs Committee Ranking Member Richard Blumenthal (D-CT) released a statement on the exemptions. “The latest Administration hiring freeze announcement still falls short. While I’m encouraged the President responded to our concerns by exempting certain VA personnel, only a clear, unequivocal statement to exempt all VA employees from the hiring freeze will reassure me—and veterans—they will receive the care and benefits they need and deserve. The exemptions listed yesterday provide more questions than answers and fail to include key personnel, including Veterans Benefits Administration employees. The Trump Administration is going to try to confuse the issue with a lot of vague assurances. We need a clear commitment every VA employee is exempt—effective immediately. Moreover, the Trump Administration must address the offers it has already rescinded that are now exempt.”

Blumenthal and 24 Democratic Senators also signed a letter to that effect, stressing concerns about the negative impact the hiring freeze will have on the delivery of veterans’ health care and benefits nationwide “if not quickly reversed.” Blumenthal also pressed Doug Collins (R-GA), Trump’s nominee for VA Secretary, to push back against a hiring freeze at VA, if his nomination is confirmed: “This is going to be a first test of your leadership.”

“We’ll take a look at the current levels of employees that we have and where they’re properly located,” Collins said, adding that he was “still examining” the freeze’s impact on the VA. “We will work under the Executive Order [Trump] has given us.” 

Blumenthal argued that the new exemptions exclude a number of critical positions at VA. Among them include all positions at the Veterans Benefits Administration and National Cemetery Administration, which provide veterans’ claims processing, survivor benefits, GI Bill education benefits, and burial scheduling and operations; many nonclinical positions critical to VA hospital functioning, including patient advocates, food service workers, and chaplains; and positions relating to construction project management for new hospitals and clinics, new nursing homes, new cemetery construction, leases, and repairs to existing VA facilities.

The US Department of Veterans Affairs (VA) has outlined > 300,000 exemptions to the federal hiring freeze to fill essential benefits and health positions. The exempted positions are primarily medical support staff. While the exemptions include pharmacists, physicians and nurses were not included. The day after taking office for the second time, President Trump signed an Executive Order implementing a “freeze on the hiring of Federal civilian employees, to be applied throughout the executive branch” but left many of the details to individual agencies.

Set to last 90 days, the hiring freeze forced Federal agencies to develop plans to reduce the size of their workforces through efficiencies and attrition, Trump said. These agencies would also not be able to hire contractors.

Three days later, however, the VA responded “Following successful implementation of President Trump’s federal hiring freeze, the Department of Veterans Affairs announced several exemptions to the policy. These exemptions clarify the department’s ability to continue filling essential positions that provide health care and other vital services to Veterans and VA beneficiaries.”

This allowed > 304,000 jobs to be exempt from the freeze. Almost 92% of the VA’s 450,000 employees work in health care and health administration and support services. Most of the exemptions involve support staff. No physicians, mental health professionals or nursing positions are on the list. However, it does include 12,622 pharmacists and 5,975 pharmacy technicians. 

The VA worked in accordance with the White House and Office of Personnel Management to develop the updated guidance, Acting Veterans Affairs Secretary Todd Hunter said. In a Jan. 21 memo, Hunter wrote: "Positions critical to delivering care to veterans in the Veteran[s] Health Administration ... are exempted under the category of public safety.”

According to Hunter's memo, no other vacancies that existed as of midday Monday will be filled. Candidates who received job offers before noon on Jan. 20 and have a start date on or before Feb. 8 will be onboarded, while those with a start date after Feb. 8—or one that is undetermined—will have their offers rescinded.

The first Trump Administration began the same way in 2017, initiating a freeze on Federal hiring and receiving a similar response from the VA. In 2017, the hiring of doctors and nurses continued while that freeze was in effect, but onboarding of new support and administrative staff was not. Then-Secretary of Veterans Affairs Dr. David J. Shulkin said, “VA is committed to serving veterans, but at the same time improving efficiency and reducing bureaucracy.” 

The current Executive Order states it “shall not adversely impact veterans’ benefits and does not apply to positions related to public safety” (or military personnel, immigration enforcement, and national security). It also says it does not adversely impact the provision of Social Security, Medicare, or Veterans’ benefits. 

“Under President Trump’s leadership, VA will always do what is necessary to provide America’s Veterans with the benefits and services they have earned. The targeted hiring-freeze exemptions announced today underscore that fact,” said VA Director of Media Affairs Morgan Ackley.  

Some in Congress feel the VA should be doing more, though, and are pushing for an exemption of all VA employees. On Friday, Senate Veterans’ Affairs Committee Ranking Member Richard Blumenthal (D-CT) released a statement on the exemptions. “The latest Administration hiring freeze announcement still falls short. While I’m encouraged the President responded to our concerns by exempting certain VA personnel, only a clear, unequivocal statement to exempt all VA employees from the hiring freeze will reassure me—and veterans—they will receive the care and benefits they need and deserve. The exemptions listed yesterday provide more questions than answers and fail to include key personnel, including Veterans Benefits Administration employees. The Trump Administration is going to try to confuse the issue with a lot of vague assurances. We need a clear commitment every VA employee is exempt—effective immediately. Moreover, the Trump Administration must address the offers it has already rescinded that are now exempt.”

Blumenthal and 24 Democratic Senators also signed a letter to that effect, stressing concerns about the negative impact the hiring freeze will have on the delivery of veterans’ health care and benefits nationwide “if not quickly reversed.” Blumenthal also pressed Doug Collins (R-GA), Trump’s nominee for VA Secretary, to push back against a hiring freeze at VA, if his nomination is confirmed: “This is going to be a first test of your leadership.”

“We’ll take a look at the current levels of employees that we have and where they’re properly located,” Collins said, adding that he was “still examining” the freeze’s impact on the VA. “We will work under the Executive Order [Trump] has given us.” 

Blumenthal argued that the new exemptions exclude a number of critical positions at VA. Among them include all positions at the Veterans Benefits Administration and National Cemetery Administration, which provide veterans’ claims processing, survivor benefits, GI Bill education benefits, and burial scheduling and operations; many nonclinical positions critical to VA hospital functioning, including patient advocates, food service workers, and chaplains; and positions relating to construction project management for new hospitals and clinics, new nursing homes, new cemetery construction, leases, and repairs to existing VA facilities.

The US Department of Veterans Affairs (VA) has outlined > 300,000 exemptions to the federal hiring freeze to fill essential benefits and health positions. The exempted positions are primarily medical support staff. While the exemptions include pharmacists, physicians and nurses were not included. The day after taking office for the second time, President Trump signed an Executive Order implementing a “freeze on the hiring of Federal civilian employees, to be applied throughout the executive branch” but left many of the details to individual agencies.

Set to last 90 days, the hiring freeze forced Federal agencies to develop plans to reduce the size of their workforces through efficiencies and attrition, Trump said. These agencies would also not be able to hire contractors.

Three days later, however, the VA responded “Following successful implementation of President Trump’s federal hiring freeze, the Department of Veterans Affairs announced several exemptions to the policy. These exemptions clarify the department’s ability to continue filling essential positions that provide health care and other vital services to Veterans and VA beneficiaries.”

This allowed > 304,000 jobs to be exempt from the freeze. Almost 92% of the VA’s 450,000 employees work in health care and health administration and support services. Most of the exemptions involve support staff. No physicians, mental health professionals or nursing positions are on the list. However, it does include 12,622 pharmacists and 5,975 pharmacy technicians. 

The VA worked in accordance with the White House and Office of Personnel Management to develop the updated guidance, Acting Veterans Affairs Secretary Todd Hunter said. In a Jan. 21 memo, Hunter wrote: "Positions critical to delivering care to veterans in the Veteran[s] Health Administration ... are exempted under the category of public safety.”

According to Hunter's memo, no other vacancies that existed as of midday Monday will be filled. Candidates who received job offers before noon on Jan. 20 and have a start date on or before Feb. 8 will be onboarded, while those with a start date after Feb. 8—or one that is undetermined—will have their offers rescinded.

The first Trump Administration began the same way in 2017, initiating a freeze on Federal hiring and receiving a similar response from the VA. In 2017, the hiring of doctors and nurses continued while that freeze was in effect, but onboarding of new support and administrative staff was not. Then-Secretary of Veterans Affairs Dr. David J. Shulkin said, “VA is committed to serving veterans, but at the same time improving efficiency and reducing bureaucracy.” 

The current Executive Order states it “shall not adversely impact veterans’ benefits and does not apply to positions related to public safety” (or military personnel, immigration enforcement, and national security). It also says it does not adversely impact the provision of Social Security, Medicare, or Veterans’ benefits. 

“Under President Trump’s leadership, VA will always do what is necessary to provide America’s Veterans with the benefits and services they have earned. The targeted hiring-freeze exemptions announced today underscore that fact,” said VA Director of Media Affairs Morgan Ackley.  

Some in Congress feel the VA should be doing more, though, and are pushing for an exemption of all VA employees. On Friday, Senate Veterans’ Affairs Committee Ranking Member Richard Blumenthal (D-CT) released a statement on the exemptions. “The latest Administration hiring freeze announcement still falls short. While I’m encouraged the President responded to our concerns by exempting certain VA personnel, only a clear, unequivocal statement to exempt all VA employees from the hiring freeze will reassure me—and veterans—they will receive the care and benefits they need and deserve. The exemptions listed yesterday provide more questions than answers and fail to include key personnel, including Veterans Benefits Administration employees. The Trump Administration is going to try to confuse the issue with a lot of vague assurances. We need a clear commitment every VA employee is exempt—effective immediately. Moreover, the Trump Administration must address the offers it has already rescinded that are now exempt.”

Blumenthal and 24 Democratic Senators also signed a letter to that effect, stressing concerns about the negative impact the hiring freeze will have on the delivery of veterans’ health care and benefits nationwide “if not quickly reversed.” Blumenthal also pressed Doug Collins (R-GA), Trump’s nominee for VA Secretary, to push back against a hiring freeze at VA, if his nomination is confirmed: “This is going to be a first test of your leadership.”

“We’ll take a look at the current levels of employees that we have and where they’re properly located,” Collins said, adding that he was “still examining” the freeze’s impact on the VA. “We will work under the Executive Order [Trump] has given us.” 

Blumenthal argued that the new exemptions exclude a number of critical positions at VA. Among them include all positions at the Veterans Benefits Administration and National Cemetery Administration, which provide veterans’ claims processing, survivor benefits, GI Bill education benefits, and burial scheduling and operations; many nonclinical positions critical to VA hospital functioning, including patient advocates, food service workers, and chaplains; and positions relating to construction project management for new hospitals and clinics, new nursing homes, new cemetery construction, leases, and repairs to existing VA facilities.

New research, with the caveat of a relatively short follow-up, adds to encouraging data showing an overall low risk of the development of thyroid cancer associated with glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment.

However, a notably increased rate of thyroid cancer detections limited only to the first year after drug initiation — but not later, coupled with an increased rate of thyroid cancer screening during that period, raises the suggestion that a thyroid cancer concern among the millions of patients taking the immensely popular drugs could exacerbate the already problematic over-detection of incidental thyroid cancers.

“Our study confirms the increased likelihood of being diagnosed with what appears to be low-risk thyroid cancer after treatment with GLP-1 RAs — but not because patients treated with GLP-1 RAs are more likely to develop thyroid cancer but rather because they are more likely to be diagnosed with it because we, as clinicians, are more likely to look for it,” senior author Rozalina G. McCoy, MD, associate professor and associate division chief for clinical research in the Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine at the University of Maryland School of Medicine, in Baltimore, told this news organization.

The findings were published in JAMA Otolaryngology-Head & Neck Surgery.

Thyroid cancer concerns surrounding GLP-1 RAs stem from preclinical studies showing a risk for medullary thyroid cancer in rodents, resulting in a boxed warning from the US Food and Drug Administration recommending that those with a family history of the condition avoid the drugs.

More recent studies showing GLP-1 receptors in human papillary thyroid cancer cells has further raised concerns of a risk beyond medullary thyroid cancer, however, recent studies evaluating the risk have been inconclusive.

To further investigate, McCoy and colleagues evaluated claims data on 351,913 adult enrollees in Medicare Advantage and fee-for-service plans in the United States who had type 2 diabetes, a moderate risk for cardiovascular disease, and no history of thyroid cancer.

Of the patients, who were about half women, 41,112 started treatments with GLP-1 RAs; 76,093, started with dipeptidyl peptidase-4 (DPP-4) inhibitors; 43,499, with sodium-glucose cotransporter 2 (SGLT2i) inhibitors; and 191,209 with sulfonylurea therapy between January 2014 and December 2021.

After inverse probability weighting, baseline characteristics in the drug groups were well-balanced.

Overall, with median follow-up times of 660 days (range, 254-1157 days) in the GLP-1 RA group; approximately 4 years in the sulfonylurea and DPP-4 inhibitor groups; and about 2.5 years in the SGLT2 inhibitor group, the absolute risk for thyroid cancer diagnoses in the treatment groups were low, with a rate of 0.17% in the GLP-1 RA group, 0.23% in the DPP-4 inhibitor group, 0.17% in the SGLT2 inhibitor group, and 0.20% in the sulfonylurea group.

The modified intention to treat analysis concluded no increase with GLP-1 RA use in thyroid cancer risk compared with the other three diabetes drugs (hazard ratio [HR], 1.24).

 

Higher Cancers Detected in First Year Likely From Higher Screening

Importantly, the risk for thyroid cancer was significantly higher within the first year after GLP-1 RA initiation (HR, 1.85) and was also higher among patients who stayed on the medication and didn’t add other medication (HR, 2.07).

With the latency period for the development of thyroid cancer from external exposures taking several years (such as radiation, taking approximately 2.5 years), some studies in fact exclude patients diagnosed with cancers within a year of starting GLP-1s, as it is implausible for a cancer to develop so soon.

Cancers detected that early therefore are considered to likely have been found due to stepped up screening resulting from an increased concern of thyroid cancer with GLP-1 use.

In support of that theory, the study showed that those in the GLP-1 group had a significantly higher rate of receiving thyroid ultrasounds than those in the non−GLP-1 group, at 1.2% at 6 months for GLP-1RA initiators vs 0.8% for non−GLP-1 RA initiators, and an estimated 2.1% at 12 months for GLP-1RA initiators vs 1.5% for non−GLP-1RA initiators (P < .01).

Though the percentages were small, in relative terms, the 6-month rate of screening in the GLP-1 RA group is a 50% increase, and the 12-month rate represents a 40% increase, McCoy pointed out. 

“If we think about 1.2% of people getting an ultrasound in the context of over 41,000 patients, that is a lot of ultrasounds,” she said. 

“To my knowledge, this is the first study to actually look at rates of thyroid ultrasounds with GLP-1 RA initiation, so it will definitely be important to look at the trends more broadly,” McCoy added.

McCoy noted that a key caveat of the study is the relatively short follow-up of only about 2 years.

“We have not been able to follow patients for decades to know if there is risk of new thyroid cancers developing after prolonged exposure,” she said. “But we generally don’t know this for any medication until it is used by many millions of people for many decades.”

 

Consistent Findings in Recent Research

In another recent study evaluating the risk for thyroid cancer among patients receiving GLP-1s, with a longer follow-up of 3.9 years, Bjorn Pasternak, MD, PhD, of the Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, and colleagues reported similar findings — the overall risk for thyroid cancer with GLP-1s was not increased (HR, 0.93), and the risk beginning 1 year after treatment initiation was lower, at 0.83. 

However, the risk in that study only looking at the first year alone was again higher, at HR 1.47.

“Our analyses indicating a nominally increased risk restricted to the first year after starting treatment might be consistent with an increased detection of thyroid cancer among patients using GLP-1 RAs,” he told this news organization.

In addition to the short follow-up of the current study, Pasternak noted the caveat of the study’s inclusion mainly of patients who initiated the four diabetes drug groups, which is a limitation “because a high proportion of the patients with type 2 diabetes in routine care who start GLP-1 RAs have started it as their third, fourth, or even fifth diabetes drug, especially if they have had diabetes for some time.”

“To capture a larger proportion of the full population of GLP-1 RA users, it would have been preferable to create three different cohorts for the purpose of this study and investigate them separately, including GLP-1 vs DPP4i; GLP-1 vs SGLT2i; GLP-1 vs sulfonylurea,” he said.

 

Rise in Incidental Thyroid Cancer Detection, An Ongoing Concern

The advent of more advanced imaging and thyroid cancer testing in recent years has already led to a significant problem of over-detection and sometimes over-treatment of incidental, small thyroid cancers that will likely remain harmless in the majority of patients. 

With approximately 64 million prescriptions of GLP-1 RAs dispensed between 2000 and 2015 and the percentage increasing at a rate of about 10%-30% per year, increased thyroid testing among those patients could indeed add to the problem.

Meanwhile, thyroid testing is currently not recommended for patients on GLP-1s who do not have a thyroid cancer risk, and the results from the current and Pasternak’s studies, as well as several other recent studies, appear to support those recommendations.

“Collectively, these reassuring data could potentially help reduce [thyroid cancer] over-detection and screening,” Pasternak said. 

McCoy echoed that the evidence indicates that “for the vast majority of people there is no indication that GLP-1 RA causes thyroid cancer.”

She underscored that overdiagnosis can have important implications, sharing her own personal experience on the receiving end of a cancer diagnosis.

“Overdiagnosis of these low-risk thyroid cancers may ultimately lead to more harm for the patient than not making the diagnosis, since surgery for thyroid cancer carries real risks (including of death) and there are downstream consequences to having your thyroid removed and relying on lifelong hormone replacement,” McCoy said.

“As a cancer survivor myself, though of lymphoma, not thyroid cancer, I also know the profound impact that a cancer diagnosis has on the individual and their loved ones,” McCoy said.

“It is not something I would wish for anyone, which is why I always speak to my patients about searching for something we may not want to — or need to — find.”

The authors and Pasternak had no disclosures to report.

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

New research, with the caveat of a relatively short follow-up, adds to encouraging data showing an overall low risk of the development of thyroid cancer associated with glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment.

However, a notably increased rate of thyroid cancer detections limited only to the first year after drug initiation — but not later, coupled with an increased rate of thyroid cancer screening during that period, raises the suggestion that a thyroid cancer concern among the millions of patients taking the immensely popular drugs could exacerbate the already problematic over-detection of incidental thyroid cancers.

“Our study confirms the increased likelihood of being diagnosed with what appears to be low-risk thyroid cancer after treatment with GLP-1 RAs — but not because patients treated with GLP-1 RAs are more likely to develop thyroid cancer but rather because they are more likely to be diagnosed with it because we, as clinicians, are more likely to look for it,” senior author Rozalina G. McCoy, MD, associate professor and associate division chief for clinical research in the Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine at the University of Maryland School of Medicine, in Baltimore, told this news organization.

The findings were published in JAMA Otolaryngology-Head & Neck Surgery.

Thyroid cancer concerns surrounding GLP-1 RAs stem from preclinical studies showing a risk for medullary thyroid cancer in rodents, resulting in a boxed warning from the US Food and Drug Administration recommending that those with a family history of the condition avoid the drugs.

More recent studies showing GLP-1 receptors in human papillary thyroid cancer cells has further raised concerns of a risk beyond medullary thyroid cancer, however, recent studies evaluating the risk have been inconclusive.

To further investigate, McCoy and colleagues evaluated claims data on 351,913 adult enrollees in Medicare Advantage and fee-for-service plans in the United States who had type 2 diabetes, a moderate risk for cardiovascular disease, and no history of thyroid cancer.

Of the patients, who were about half women, 41,112 started treatments with GLP-1 RAs; 76,093, started with dipeptidyl peptidase-4 (DPP-4) inhibitors; 43,499, with sodium-glucose cotransporter 2 (SGLT2i) inhibitors; and 191,209 with sulfonylurea therapy between January 2014 and December 2021.

After inverse probability weighting, baseline characteristics in the drug groups were well-balanced.

Overall, with median follow-up times of 660 days (range, 254-1157 days) in the GLP-1 RA group; approximately 4 years in the sulfonylurea and DPP-4 inhibitor groups; and about 2.5 years in the SGLT2 inhibitor group, the absolute risk for thyroid cancer diagnoses in the treatment groups were low, with a rate of 0.17% in the GLP-1 RA group, 0.23% in the DPP-4 inhibitor group, 0.17% in the SGLT2 inhibitor group, and 0.20% in the sulfonylurea group.

The modified intention to treat analysis concluded no increase with GLP-1 RA use in thyroid cancer risk compared with the other three diabetes drugs (hazard ratio [HR], 1.24).

 

Higher Cancers Detected in First Year Likely From Higher Screening

Importantly, the risk for thyroid cancer was significantly higher within the first year after GLP-1 RA initiation (HR, 1.85) and was also higher among patients who stayed on the medication and didn’t add other medication (HR, 2.07).

With the latency period for the development of thyroid cancer from external exposures taking several years (such as radiation, taking approximately 2.5 years), some studies in fact exclude patients diagnosed with cancers within a year of starting GLP-1s, as it is implausible for a cancer to develop so soon.

Cancers detected that early therefore are considered to likely have been found due to stepped up screening resulting from an increased concern of thyroid cancer with GLP-1 use.

In support of that theory, the study showed that those in the GLP-1 group had a significantly higher rate of receiving thyroid ultrasounds than those in the non−GLP-1 group, at 1.2% at 6 months for GLP-1RA initiators vs 0.8% for non−GLP-1 RA initiators, and an estimated 2.1% at 12 months for GLP-1RA initiators vs 1.5% for non−GLP-1RA initiators (P < .01).

Though the percentages were small, in relative terms, the 6-month rate of screening in the GLP-1 RA group is a 50% increase, and the 12-month rate represents a 40% increase, McCoy pointed out. 

“If we think about 1.2% of people getting an ultrasound in the context of over 41,000 patients, that is a lot of ultrasounds,” she said. 

“To my knowledge, this is the first study to actually look at rates of thyroid ultrasounds with GLP-1 RA initiation, so it will definitely be important to look at the trends more broadly,” McCoy added.

McCoy noted that a key caveat of the study is the relatively short follow-up of only about 2 years.

“We have not been able to follow patients for decades to know if there is risk of new thyroid cancers developing after prolonged exposure,” she said. “But we generally don’t know this for any medication until it is used by many millions of people for many decades.”

 

Consistent Findings in Recent Research

In another recent study evaluating the risk for thyroid cancer among patients receiving GLP-1s, with a longer follow-up of 3.9 years, Bjorn Pasternak, MD, PhD, of the Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, and colleagues reported similar findings — the overall risk for thyroid cancer with GLP-1s was not increased (HR, 0.93), and the risk beginning 1 year after treatment initiation was lower, at 0.83. 

However, the risk in that study only looking at the first year alone was again higher, at HR 1.47.

“Our analyses indicating a nominally increased risk restricted to the first year after starting treatment might be consistent with an increased detection of thyroid cancer among patients using GLP-1 RAs,” he told this news organization.

In addition to the short follow-up of the current study, Pasternak noted the caveat of the study’s inclusion mainly of patients who initiated the four diabetes drug groups, which is a limitation “because a high proportion of the patients with type 2 diabetes in routine care who start GLP-1 RAs have started it as their third, fourth, or even fifth diabetes drug, especially if they have had diabetes for some time.”

“To capture a larger proportion of the full population of GLP-1 RA users, it would have been preferable to create three different cohorts for the purpose of this study and investigate them separately, including GLP-1 vs DPP4i; GLP-1 vs SGLT2i; GLP-1 vs sulfonylurea,” he said.

 

Rise in Incidental Thyroid Cancer Detection, An Ongoing Concern

The advent of more advanced imaging and thyroid cancer testing in recent years has already led to a significant problem of over-detection and sometimes over-treatment of incidental, small thyroid cancers that will likely remain harmless in the majority of patients. 

With approximately 64 million prescriptions of GLP-1 RAs dispensed between 2000 and 2015 and the percentage increasing at a rate of about 10%-30% per year, increased thyroid testing among those patients could indeed add to the problem.

Meanwhile, thyroid testing is currently not recommended for patients on GLP-1s who do not have a thyroid cancer risk, and the results from the current and Pasternak’s studies, as well as several other recent studies, appear to support those recommendations.

“Collectively, these reassuring data could potentially help reduce [thyroid cancer] over-detection and screening,” Pasternak said. 

McCoy echoed that the evidence indicates that “for the vast majority of people there is no indication that GLP-1 RA causes thyroid cancer.”

She underscored that overdiagnosis can have important implications, sharing her own personal experience on the receiving end of a cancer diagnosis.

“Overdiagnosis of these low-risk thyroid cancers may ultimately lead to more harm for the patient than not making the diagnosis, since surgery for thyroid cancer carries real risks (including of death) and there are downstream consequences to having your thyroid removed and relying on lifelong hormone replacement,” McCoy said.

“As a cancer survivor myself, though of lymphoma, not thyroid cancer, I also know the profound impact that a cancer diagnosis has on the individual and their loved ones,” McCoy said.

“It is not something I would wish for anyone, which is why I always speak to my patients about searching for something we may not want to — or need to — find.”

The authors and Pasternak had no disclosures to report.

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

New research, with the caveat of a relatively short follow-up, adds to encouraging data showing an overall low risk of the development of thyroid cancer associated with glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment.

However, a notably increased rate of thyroid cancer detections limited only to the first year after drug initiation — but not later, coupled with an increased rate of thyroid cancer screening during that period, raises the suggestion that a thyroid cancer concern among the millions of patients taking the immensely popular drugs could exacerbate the already problematic over-detection of incidental thyroid cancers.

“Our study confirms the increased likelihood of being diagnosed with what appears to be low-risk thyroid cancer after treatment with GLP-1 RAs — but not because patients treated with GLP-1 RAs are more likely to develop thyroid cancer but rather because they are more likely to be diagnosed with it because we, as clinicians, are more likely to look for it,” senior author Rozalina G. McCoy, MD, associate professor and associate division chief for clinical research in the Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine at the University of Maryland School of Medicine, in Baltimore, told this news organization.

The findings were published in JAMA Otolaryngology-Head & Neck Surgery.

Thyroid cancer concerns surrounding GLP-1 RAs stem from preclinical studies showing a risk for medullary thyroid cancer in rodents, resulting in a boxed warning from the US Food and Drug Administration recommending that those with a family history of the condition avoid the drugs.

More recent studies showing GLP-1 receptors in human papillary thyroid cancer cells has further raised concerns of a risk beyond medullary thyroid cancer, however, recent studies evaluating the risk have been inconclusive.

To further investigate, McCoy and colleagues evaluated claims data on 351,913 adult enrollees in Medicare Advantage and fee-for-service plans in the United States who had type 2 diabetes, a moderate risk for cardiovascular disease, and no history of thyroid cancer.

Of the patients, who were about half women, 41,112 started treatments with GLP-1 RAs; 76,093, started with dipeptidyl peptidase-4 (DPP-4) inhibitors; 43,499, with sodium-glucose cotransporter 2 (SGLT2i) inhibitors; and 191,209 with sulfonylurea therapy between January 2014 and December 2021.

After inverse probability weighting, baseline characteristics in the drug groups were well-balanced.

Overall, with median follow-up times of 660 days (range, 254-1157 days) in the GLP-1 RA group; approximately 4 years in the sulfonylurea and DPP-4 inhibitor groups; and about 2.5 years in the SGLT2 inhibitor group, the absolute risk for thyroid cancer diagnoses in the treatment groups were low, with a rate of 0.17% in the GLP-1 RA group, 0.23% in the DPP-4 inhibitor group, 0.17% in the SGLT2 inhibitor group, and 0.20% in the sulfonylurea group.

The modified intention to treat analysis concluded no increase with GLP-1 RA use in thyroid cancer risk compared with the other three diabetes drugs (hazard ratio [HR], 1.24).

 

Higher Cancers Detected in First Year Likely From Higher Screening

Importantly, the risk for thyroid cancer was significantly higher within the first year after GLP-1 RA initiation (HR, 1.85) and was also higher among patients who stayed on the medication and didn’t add other medication (HR, 2.07).

With the latency period for the development of thyroid cancer from external exposures taking several years (such as radiation, taking approximately 2.5 years), some studies in fact exclude patients diagnosed with cancers within a year of starting GLP-1s, as it is implausible for a cancer to develop so soon.

Cancers detected that early therefore are considered to likely have been found due to stepped up screening resulting from an increased concern of thyroid cancer with GLP-1 use.

In support of that theory, the study showed that those in the GLP-1 group had a significantly higher rate of receiving thyroid ultrasounds than those in the non−GLP-1 group, at 1.2% at 6 months for GLP-1RA initiators vs 0.8% for non−GLP-1 RA initiators, and an estimated 2.1% at 12 months for GLP-1RA initiators vs 1.5% for non−GLP-1RA initiators (P < .01).

Though the percentages were small, in relative terms, the 6-month rate of screening in the GLP-1 RA group is a 50% increase, and the 12-month rate represents a 40% increase, McCoy pointed out. 

“If we think about 1.2% of people getting an ultrasound in the context of over 41,000 patients, that is a lot of ultrasounds,” she said. 

“To my knowledge, this is the first study to actually look at rates of thyroid ultrasounds with GLP-1 RA initiation, so it will definitely be important to look at the trends more broadly,” McCoy added.

McCoy noted that a key caveat of the study is the relatively short follow-up of only about 2 years.

“We have not been able to follow patients for decades to know if there is risk of new thyroid cancers developing after prolonged exposure,” she said. “But we generally don’t know this for any medication until it is used by many millions of people for many decades.”

 

Consistent Findings in Recent Research

In another recent study evaluating the risk for thyroid cancer among patients receiving GLP-1s, with a longer follow-up of 3.9 years, Bjorn Pasternak, MD, PhD, of the Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, and colleagues reported similar findings — the overall risk for thyroid cancer with GLP-1s was not increased (HR, 0.93), and the risk beginning 1 year after treatment initiation was lower, at 0.83. 

However, the risk in that study only looking at the first year alone was again higher, at HR 1.47.

“Our analyses indicating a nominally increased risk restricted to the first year after starting treatment might be consistent with an increased detection of thyroid cancer among patients using GLP-1 RAs,” he told this news organization.

In addition to the short follow-up of the current study, Pasternak noted the caveat of the study’s inclusion mainly of patients who initiated the four diabetes drug groups, which is a limitation “because a high proportion of the patients with type 2 diabetes in routine care who start GLP-1 RAs have started it as their third, fourth, or even fifth diabetes drug, especially if they have had diabetes for some time.”

“To capture a larger proportion of the full population of GLP-1 RA users, it would have been preferable to create three different cohorts for the purpose of this study and investigate them separately, including GLP-1 vs DPP4i; GLP-1 vs SGLT2i; GLP-1 vs sulfonylurea,” he said.

 

Rise in Incidental Thyroid Cancer Detection, An Ongoing Concern

The advent of more advanced imaging and thyroid cancer testing in recent years has already led to a significant problem of over-detection and sometimes over-treatment of incidental, small thyroid cancers that will likely remain harmless in the majority of patients. 

With approximately 64 million prescriptions of GLP-1 RAs dispensed between 2000 and 2015 and the percentage increasing at a rate of about 10%-30% per year, increased thyroid testing among those patients could indeed add to the problem.

Meanwhile, thyroid testing is currently not recommended for patients on GLP-1s who do not have a thyroid cancer risk, and the results from the current and Pasternak’s studies, as well as several other recent studies, appear to support those recommendations.

“Collectively, these reassuring data could potentially help reduce [thyroid cancer] over-detection and screening,” Pasternak said. 

McCoy echoed that the evidence indicates that “for the vast majority of people there is no indication that GLP-1 RA causes thyroid cancer.”

She underscored that overdiagnosis can have important implications, sharing her own personal experience on the receiving end of a cancer diagnosis.

“Overdiagnosis of these low-risk thyroid cancers may ultimately lead to more harm for the patient than not making the diagnosis, since surgery for thyroid cancer carries real risks (including of death) and there are downstream consequences to having your thyroid removed and relying on lifelong hormone replacement,” McCoy said.

“As a cancer survivor myself, though of lymphoma, not thyroid cancer, I also know the profound impact that a cancer diagnosis has on the individual and their loved ones,” McCoy said.

“It is not something I would wish for anyone, which is why I always speak to my patients about searching for something we may not want to — or need to — find.”

The authors and Pasternak had no disclosures to report.

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

The use of surrogate endpoints to predict overall survival in oncology trials has been vigorously debated in the oncology community. 

In multiple studies, we have shown that the correlation of surrogate endpoints with overall survival has been weak and, in most cases, inadequate. However, others have made arguments against using overall survival as the gold standard endpoint for cancer drug trials. These arguments include claims that overall survival is not a feasible endpoint for pivotal cancer drug trials and that negative overall survival results may be unreliable.

In this column, we counter some of these arguments from the perspective of an oncologist who treats cancer and is engaged in oncology research and a patient advocate with lived experience of cancer.

Argument: Overall survival is not the only meaningful clinical endpoint. Response rates and progression-free survival also are important clinical endpoints because patients feel good when their tumor shrinks or they have more time without disease progression. Both situations can improve patients’ quality of life. 

Response: On the face of it, this argument sounds reasonable, but it treats response rates and progression-free survival as clinical endpoints rather than surrogate endpoints that need to be validated. A patient would surely welcome news that treatment has reduced the size of their tumor and would feel dismayed if the tumor is growing. However, these reactions rest on the belief that these changes signal recovery in the case of a shrinking tumor, or worsening symptoms in the case of a growing tumor, neither of which may be true. 

“Disease progression” and “progression-free survival” were developed as technical terms to signify whether a therapy in a phase 2 clinical trial was sufficiently promising to advance to phase 3. The terms were not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. In clinical trials, a progression event is defined as an increase in the sum of tumor diameters by more than 20%, or the appearance of a new lesion. These are both arbitrary benchmarks that in no way imply that a patient’s subjective experience of symptoms or their survival time would differ widely between a tumor growth of 19% vs 21%, or if a new, tiny lesion develops.

Of course, disease progression sometimes does affect a patient’s quality of life, but trials treat all progression events equally. An event in the brain that affects the patient’s ability to walk and an asymptomatic tumor growth in the lung from 1 cm to 1.3 cm are both considered disease progression in trials.

Patients care about progression-free survival because they mistakenly believe that an improvement will probably lead to improved overall survival or quality of life. But overall survival and quality of life can actually be affected detrimentally, despite progression-free survival gains, because the patient may experience treatment-related physical and financial toxicity without clinical benefit. Conversely, it is possible to have better overall survival and quality of life without any improvement in progression-free survival.

With response rates, the relationships to overall survival and quality of life are even weaker. Because progression-free survival and response rates do not represent clinical benefit, they cannot be considered clinical endpoints. They are surrogate endpoints that need to be validated.

A patient will reasonably welcome a treatment-related change that improves the prospect of living a longer life or enduring less suffering but should not be misled when these outcomes have not been demonstrated as being clinically beneficial.

Argument: It is not ethical to wait for overall survival when there is an unmet need.

Response: The phrase “unmet need” is used to represent the lack of effective treatment options for a particular condition. Regulators may expedite approval of a new drug that is intended to fulfil the need because waiting for overall survival may not seem ethical in these settings. 

In reality, however, the term is used inconsistently, both when the need is either questionable (the indication is indolent) or the need is real but one or more treatment options already exist. 

When the need for a drug with clinical benefit is genuinely unmet, presenting patients with just any drug is unethical; their need will continue to exist despite drug approvals if survival is not improved. In fact, approving ineffective drugs can impede the development of drugs that work.

Argument: Overall survival is not a practical endpoint for drug trials for rare cancers. 

Response: This argument has some practical validity because the low prevalence of a rare cancer may limit study recruitment opportunities. From an equity perspective, however, patients with rare cancers are no less deserving of treatments based on meaningful evidence of safety and efficacy than are patients with common cancers. Like any other patient with cancer, they should know those treatments have shown the potential for an overall survival or quality of life benefit before undergoing potentially toxic treatments. 

Several trials, such as FIRM-ACT, VIT-0910, AEWS0031, and rEECur, have shown that international collaboration makes randomized clinical trials with an endpoint of overall survival possible for most rare cancers. We support offering early access via accelerated approval when scientific evidence suggests a drug has potential benefit for patients, but the trial should be followed to confirm an overall survival benefit and the drug should be withdrawn if an overall survival benefit is lacking. 

Argument: The point of measuring overall survival is to ensure that the treatment does not worsen overall survival. 

Response: This argument is frequently made, even by regulators. However, unless a drug is tested in a justified noninferiority design trial where the aim is to determine whether it provides compensatory benefits — easier administration, lower cost, or fewer side effects than the alternative — the goal of new cancer drugs is to improve survival. Merely “not worsening survival” is incongruent with medicine’s fundamental goal of benevolence. All drugs have toxicities, some of which can be fatal. Recommending a treatment with toxicities because it did not worsen survival would harm patients and go against the Hippocratic Oath.

Argument: Overall survival in this trial was negative, but this was probably a false-negative finding. We expect future trials will be positive. 

Response: When a drug fails to improve overall survival, some experts will argue that it was a false-negative result and a future trial will be positive. For instance, to explain the negative overall survival findings in a 2020 confirmatory trial, the researchers cited a subgroup analysis in which the drug received accelerated approval based on early exploratory results. However, the subgroup analysis violated the statistical plan and raised the likelihood that the early trial’s favorable outcome was false-positive.

A second trend that increases the likelihood of false-positives is when the same anticancer medications are studied across multiple trials. If we run dozens of trials of the same drug, some of them will eventually be positive by chance alone. 

Dismissing a negative overall survival finding as a statistical artifact puts patients at risk because oncologists may continue to use the drug, despite it providing no discernable clinical benefit to patients. 

Argument: The overall survival was negative because of crossover so that patients in the control arm received the therapy at progression. 

Response: Highly effective drugs will continue to show overall survival gains despite crossover — that is, when patients in the control arm receive the experimental drug at the time of progression.

For example, a trial evaluating the addition of pertuzumab in first-line HER2-positive metastatic breast cancer allowed crossover and still showed a significant overall survival benefit. Another trial evaluating sunitinib vs placebo in advanced gastrointestinal stromal tumors showed a significant overall survival improvement despite 80% of patients in the placebo arm crossing over to sunitinib at progression.

However, in the SONIA trial, receiving cyclin-dependent kinase 4/6 inhibitors as first-line treatment of metastatic hormone receptor–positive breast cancer did not improve survival and added toxicities compared with receipt of the same agents as second-line treatment.

If crossover negates an overall survival benefit, this implies that patients in the experimental arm who received the drug upfront and patients in control arm who get the drug only at progression have no difference in survival times. If the survival outcomes in the groups are similar, that is evidence that the new drug should be given only to those who need treatment at the time of progression and not to everyone upfront. 

Giving patients the drug at the time of progression would spare patients toxicities, preserve efficacy, and save health systems costs.

Argument: Although overall survival is negative in the confirmatory trial, the clinical practice guidelines recommend using the drug, and the guidelines should be followed.

Response: We cannot ignore results of a confirmatory trial just because the drug is already in the guidelines. Guidelines should be updated on the basis of the latest evidence, rather than clinical practice being dictated by outdated guidelines. When a drug given accelerated approval appears in the guidelines, the confidence level of the evidence should be rated low until confirmatory results are available. If a confirmatory trial shows that overall survival does not improve, the guidelines should be quickly updated. However, even if they are not, physicians should not just blindly follow the guidelines.

Furthermore, practitioners should be aware that members of oncology guidelines committees often have financial conflicts of interest with pharmaceutical companies, which the literature shows can bias guideline recommendations.

 

The Bottom Line

We believe that despite arguments put forward against relying on or measuring overall survival, it continues to be the most patient-centric marker of clinical benefit. Patients deserve to know that the cancer drugs their oncologists recommend will contribute to a longer or better life.

Bishal Gyawali, Associate Professor, Department of Oncology and Department of Public Health Sciences; Scientist, Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada; Affiliated Faculty at the Program on Regulation, Therapeutics, and Law, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, has disclosed the financial relationship by receiving consulting fees from Vivio Health. Sharon Batt, Cancer survivor and patient advocate; Adjunct professor, Department of Bioethics and Department of Political Science, Dalhousie University, Halifax, Nova Scotia, Canada, has disclosed no relevant financial relationships.

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

The use of surrogate endpoints to predict overall survival in oncology trials has been vigorously debated in the oncology community. 

In multiple studies, we have shown that the correlation of surrogate endpoints with overall survival has been weak and, in most cases, inadequate. However, others have made arguments against using overall survival as the gold standard endpoint for cancer drug trials. These arguments include claims that overall survival is not a feasible endpoint for pivotal cancer drug trials and that negative overall survival results may be unreliable.

In this column, we counter some of these arguments from the perspective of an oncologist who treats cancer and is engaged in oncology research and a patient advocate with lived experience of cancer.

Argument: Overall survival is not the only meaningful clinical endpoint. Response rates and progression-free survival also are important clinical endpoints because patients feel good when their tumor shrinks or they have more time without disease progression. Both situations can improve patients’ quality of life. 

Response: On the face of it, this argument sounds reasonable, but it treats response rates and progression-free survival as clinical endpoints rather than surrogate endpoints that need to be validated. A patient would surely welcome news that treatment has reduced the size of their tumor and would feel dismayed if the tumor is growing. However, these reactions rest on the belief that these changes signal recovery in the case of a shrinking tumor, or worsening symptoms in the case of a growing tumor, neither of which may be true. 

“Disease progression” and “progression-free survival” were developed as technical terms to signify whether a therapy in a phase 2 clinical trial was sufficiently promising to advance to phase 3. The terms were not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. In clinical trials, a progression event is defined as an increase in the sum of tumor diameters by more than 20%, or the appearance of a new lesion. These are both arbitrary benchmarks that in no way imply that a patient’s subjective experience of symptoms or their survival time would differ widely between a tumor growth of 19% vs 21%, or if a new, tiny lesion develops.

Of course, disease progression sometimes does affect a patient’s quality of life, but trials treat all progression events equally. An event in the brain that affects the patient’s ability to walk and an asymptomatic tumor growth in the lung from 1 cm to 1.3 cm are both considered disease progression in trials.

Patients care about progression-free survival because they mistakenly believe that an improvement will probably lead to improved overall survival or quality of life. But overall survival and quality of life can actually be affected detrimentally, despite progression-free survival gains, because the patient may experience treatment-related physical and financial toxicity without clinical benefit. Conversely, it is possible to have better overall survival and quality of life without any improvement in progression-free survival.

With response rates, the relationships to overall survival and quality of life are even weaker. Because progression-free survival and response rates do not represent clinical benefit, they cannot be considered clinical endpoints. They are surrogate endpoints that need to be validated.

A patient will reasonably welcome a treatment-related change that improves the prospect of living a longer life or enduring less suffering but should not be misled when these outcomes have not been demonstrated as being clinically beneficial.

Argument: It is not ethical to wait for overall survival when there is an unmet need.

Response: The phrase “unmet need” is used to represent the lack of effective treatment options for a particular condition. Regulators may expedite approval of a new drug that is intended to fulfil the need because waiting for overall survival may not seem ethical in these settings. 

In reality, however, the term is used inconsistently, both when the need is either questionable (the indication is indolent) or the need is real but one or more treatment options already exist. 

When the need for a drug with clinical benefit is genuinely unmet, presenting patients with just any drug is unethical; their need will continue to exist despite drug approvals if survival is not improved. In fact, approving ineffective drugs can impede the development of drugs that work.

Argument: Overall survival is not a practical endpoint for drug trials for rare cancers. 

Response: This argument has some practical validity because the low prevalence of a rare cancer may limit study recruitment opportunities. From an equity perspective, however, patients with rare cancers are no less deserving of treatments based on meaningful evidence of safety and efficacy than are patients with common cancers. Like any other patient with cancer, they should know those treatments have shown the potential for an overall survival or quality of life benefit before undergoing potentially toxic treatments. 

Several trials, such as FIRM-ACT, VIT-0910, AEWS0031, and rEECur, have shown that international collaboration makes randomized clinical trials with an endpoint of overall survival possible for most rare cancers. We support offering early access via accelerated approval when scientific evidence suggests a drug has potential benefit for patients, but the trial should be followed to confirm an overall survival benefit and the drug should be withdrawn if an overall survival benefit is lacking. 

Argument: The point of measuring overall survival is to ensure that the treatment does not worsen overall survival. 

Response: This argument is frequently made, even by regulators. However, unless a drug is tested in a justified noninferiority design trial where the aim is to determine whether it provides compensatory benefits — easier administration, lower cost, or fewer side effects than the alternative — the goal of new cancer drugs is to improve survival. Merely “not worsening survival” is incongruent with medicine’s fundamental goal of benevolence. All drugs have toxicities, some of which can be fatal. Recommending a treatment with toxicities because it did not worsen survival would harm patients and go against the Hippocratic Oath.

Argument: Overall survival in this trial was negative, but this was probably a false-negative finding. We expect future trials will be positive. 

Response: When a drug fails to improve overall survival, some experts will argue that it was a false-negative result and a future trial will be positive. For instance, to explain the negative overall survival findings in a 2020 confirmatory trial, the researchers cited a subgroup analysis in which the drug received accelerated approval based on early exploratory results. However, the subgroup analysis violated the statistical plan and raised the likelihood that the early trial’s favorable outcome was false-positive.

A second trend that increases the likelihood of false-positives is when the same anticancer medications are studied across multiple trials. If we run dozens of trials of the same drug, some of them will eventually be positive by chance alone. 

Dismissing a negative overall survival finding as a statistical artifact puts patients at risk because oncologists may continue to use the drug, despite it providing no discernable clinical benefit to patients. 

Argument: The overall survival was negative because of crossover so that patients in the control arm received the therapy at progression. 

Response: Highly effective drugs will continue to show overall survival gains despite crossover — that is, when patients in the control arm receive the experimental drug at the time of progression.

For example, a trial evaluating the addition of pertuzumab in first-line HER2-positive metastatic breast cancer allowed crossover and still showed a significant overall survival benefit. Another trial evaluating sunitinib vs placebo in advanced gastrointestinal stromal tumors showed a significant overall survival improvement despite 80% of patients in the placebo arm crossing over to sunitinib at progression.

However, in the SONIA trial, receiving cyclin-dependent kinase 4/6 inhibitors as first-line treatment of metastatic hormone receptor–positive breast cancer did not improve survival and added toxicities compared with receipt of the same agents as second-line treatment.

If crossover negates an overall survival benefit, this implies that patients in the experimental arm who received the drug upfront and patients in control arm who get the drug only at progression have no difference in survival times. If the survival outcomes in the groups are similar, that is evidence that the new drug should be given only to those who need treatment at the time of progression and not to everyone upfront. 

Giving patients the drug at the time of progression would spare patients toxicities, preserve efficacy, and save health systems costs.

Argument: Although overall survival is negative in the confirmatory trial, the clinical practice guidelines recommend using the drug, and the guidelines should be followed.

Response: We cannot ignore results of a confirmatory trial just because the drug is already in the guidelines. Guidelines should be updated on the basis of the latest evidence, rather than clinical practice being dictated by outdated guidelines. When a drug given accelerated approval appears in the guidelines, the confidence level of the evidence should be rated low until confirmatory results are available. If a confirmatory trial shows that overall survival does not improve, the guidelines should be quickly updated. However, even if they are not, physicians should not just blindly follow the guidelines.

Furthermore, practitioners should be aware that members of oncology guidelines committees often have financial conflicts of interest with pharmaceutical companies, which the literature shows can bias guideline recommendations.

 

The Bottom Line

We believe that despite arguments put forward against relying on or measuring overall survival, it continues to be the most patient-centric marker of clinical benefit. Patients deserve to know that the cancer drugs their oncologists recommend will contribute to a longer or better life.

Bishal Gyawali, Associate Professor, Department of Oncology and Department of Public Health Sciences; Scientist, Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada; Affiliated Faculty at the Program on Regulation, Therapeutics, and Law, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, has disclosed the financial relationship by receiving consulting fees from Vivio Health. Sharon Batt, Cancer survivor and patient advocate; Adjunct professor, Department of Bioethics and Department of Political Science, Dalhousie University, Halifax, Nova Scotia, Canada, has disclosed no relevant financial relationships.

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

The use of surrogate endpoints to predict overall survival in oncology trials has been vigorously debated in the oncology community. 

In multiple studies, we have shown that the correlation of surrogate endpoints with overall survival has been weak and, in most cases, inadequate. However, others have made arguments against using overall survival as the gold standard endpoint for cancer drug trials. These arguments include claims that overall survival is not a feasible endpoint for pivotal cancer drug trials and that negative overall survival results may be unreliable.

In this column, we counter some of these arguments from the perspective of an oncologist who treats cancer and is engaged in oncology research and a patient advocate with lived experience of cancer.

Argument: Overall survival is not the only meaningful clinical endpoint. Response rates and progression-free survival also are important clinical endpoints because patients feel good when their tumor shrinks or they have more time without disease progression. Both situations can improve patients’ quality of life. 

Response: On the face of it, this argument sounds reasonable, but it treats response rates and progression-free survival as clinical endpoints rather than surrogate endpoints that need to be validated. A patient would surely welcome news that treatment has reduced the size of their tumor and would feel dismayed if the tumor is growing. However, these reactions rest on the belief that these changes signal recovery in the case of a shrinking tumor, or worsening symptoms in the case of a growing tumor, neither of which may be true. 

“Disease progression” and “progression-free survival” were developed as technical terms to signify whether a therapy in a phase 2 clinical trial was sufficiently promising to advance to phase 3. The terms were not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. In clinical trials, a progression event is defined as an increase in the sum of tumor diameters by more than 20%, or the appearance of a new lesion. These are both arbitrary benchmarks that in no way imply that a patient’s subjective experience of symptoms or their survival time would differ widely between a tumor growth of 19% vs 21%, or if a new, tiny lesion develops.

Of course, disease progression sometimes does affect a patient’s quality of life, but trials treat all progression events equally. An event in the brain that affects the patient’s ability to walk and an asymptomatic tumor growth in the lung from 1 cm to 1.3 cm are both considered disease progression in trials.

Patients care about progression-free survival because they mistakenly believe that an improvement will probably lead to improved overall survival or quality of life. But overall survival and quality of life can actually be affected detrimentally, despite progression-free survival gains, because the patient may experience treatment-related physical and financial toxicity without clinical benefit. Conversely, it is possible to have better overall survival and quality of life without any improvement in progression-free survival.

With response rates, the relationships to overall survival and quality of life are even weaker. Because progression-free survival and response rates do not represent clinical benefit, they cannot be considered clinical endpoints. They are surrogate endpoints that need to be validated.

A patient will reasonably welcome a treatment-related change that improves the prospect of living a longer life or enduring less suffering but should not be misled when these outcomes have not been demonstrated as being clinically beneficial.

Argument: It is not ethical to wait for overall survival when there is an unmet need.

Response: The phrase “unmet need” is used to represent the lack of effective treatment options for a particular condition. Regulators may expedite approval of a new drug that is intended to fulfil the need because waiting for overall survival may not seem ethical in these settings. 

In reality, however, the term is used inconsistently, both when the need is either questionable (the indication is indolent) or the need is real but one or more treatment options already exist. 

When the need for a drug with clinical benefit is genuinely unmet, presenting patients with just any drug is unethical; their need will continue to exist despite drug approvals if survival is not improved. In fact, approving ineffective drugs can impede the development of drugs that work.

Argument: Overall survival is not a practical endpoint for drug trials for rare cancers. 

Response: This argument has some practical validity because the low prevalence of a rare cancer may limit study recruitment opportunities. From an equity perspective, however, patients with rare cancers are no less deserving of treatments based on meaningful evidence of safety and efficacy than are patients with common cancers. Like any other patient with cancer, they should know those treatments have shown the potential for an overall survival or quality of life benefit before undergoing potentially toxic treatments. 

Several trials, such as FIRM-ACT, VIT-0910, AEWS0031, and rEECur, have shown that international collaboration makes randomized clinical trials with an endpoint of overall survival possible for most rare cancers. We support offering early access via accelerated approval when scientific evidence suggests a drug has potential benefit for patients, but the trial should be followed to confirm an overall survival benefit and the drug should be withdrawn if an overall survival benefit is lacking. 

Argument: The point of measuring overall survival is to ensure that the treatment does not worsen overall survival. 

Response: This argument is frequently made, even by regulators. However, unless a drug is tested in a justified noninferiority design trial where the aim is to determine whether it provides compensatory benefits — easier administration, lower cost, or fewer side effects than the alternative — the goal of new cancer drugs is to improve survival. Merely “not worsening survival” is incongruent with medicine’s fundamental goal of benevolence. All drugs have toxicities, some of which can be fatal. Recommending a treatment with toxicities because it did not worsen survival would harm patients and go against the Hippocratic Oath.

Argument: Overall survival in this trial was negative, but this was probably a false-negative finding. We expect future trials will be positive. 

Response: When a drug fails to improve overall survival, some experts will argue that it was a false-negative result and a future trial will be positive. For instance, to explain the negative overall survival findings in a 2020 confirmatory trial, the researchers cited a subgroup analysis in which the drug received accelerated approval based on early exploratory results. However, the subgroup analysis violated the statistical plan and raised the likelihood that the early trial’s favorable outcome was false-positive.

A second trend that increases the likelihood of false-positives is when the same anticancer medications are studied across multiple trials. If we run dozens of trials of the same drug, some of them will eventually be positive by chance alone. 

Dismissing a negative overall survival finding as a statistical artifact puts patients at risk because oncologists may continue to use the drug, despite it providing no discernable clinical benefit to patients. 

Argument: The overall survival was negative because of crossover so that patients in the control arm received the therapy at progression. 

Response: Highly effective drugs will continue to show overall survival gains despite crossover — that is, when patients in the control arm receive the experimental drug at the time of progression.

For example, a trial evaluating the addition of pertuzumab in first-line HER2-positive metastatic breast cancer allowed crossover and still showed a significant overall survival benefit. Another trial evaluating sunitinib vs placebo in advanced gastrointestinal stromal tumors showed a significant overall survival improvement despite 80% of patients in the placebo arm crossing over to sunitinib at progression.

However, in the SONIA trial, receiving cyclin-dependent kinase 4/6 inhibitors as first-line treatment of metastatic hormone receptor–positive breast cancer did not improve survival and added toxicities compared with receipt of the same agents as second-line treatment.

If crossover negates an overall survival benefit, this implies that patients in the experimental arm who received the drug upfront and patients in control arm who get the drug only at progression have no difference in survival times. If the survival outcomes in the groups are similar, that is evidence that the new drug should be given only to those who need treatment at the time of progression and not to everyone upfront. 

Giving patients the drug at the time of progression would spare patients toxicities, preserve efficacy, and save health systems costs.

Argument: Although overall survival is negative in the confirmatory trial, the clinical practice guidelines recommend using the drug, and the guidelines should be followed.

Response: We cannot ignore results of a confirmatory trial just because the drug is already in the guidelines. Guidelines should be updated on the basis of the latest evidence, rather than clinical practice being dictated by outdated guidelines. When a drug given accelerated approval appears in the guidelines, the confidence level of the evidence should be rated low until confirmatory results are available. If a confirmatory trial shows that overall survival does not improve, the guidelines should be quickly updated. However, even if they are not, physicians should not just blindly follow the guidelines.

Furthermore, practitioners should be aware that members of oncology guidelines committees often have financial conflicts of interest with pharmaceutical companies, which the literature shows can bias guideline recommendations.

 

The Bottom Line

We believe that despite arguments put forward against relying on or measuring overall survival, it continues to be the most patient-centric marker of clinical benefit. Patients deserve to know that the cancer drugs their oncologists recommend will contribute to a longer or better life.

Bishal Gyawali, Associate Professor, Department of Oncology and Department of Public Health Sciences; Scientist, Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada; Affiliated Faculty at the Program on Regulation, Therapeutics, and Law, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, has disclosed the financial relationship by receiving consulting fees from Vivio Health. Sharon Batt, Cancer survivor and patient advocate; Adjunct professor, Department of Bioethics and Department of Political Science, Dalhousie University, Halifax, Nova Scotia, Canada, has disclosed no relevant financial relationships.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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