AVAHO

This transcript has been edited for clarity.

Today, I’m going to talk about the 2023 Food and Drug Administration regulation that requires breast density to be reported on all mammogram results nationwide, and for that report to go to both clinicians and patients. Previously this was the rule in some states, but not in others. This is important because 40%-50% of women have dense breasts. I’m going to discuss what that means for you, and for our patients.

First I’ll review what breast density is, and how it is categorized and reported, and then why it’s important and what to do with the results.

Breast density describes the appearance of the breast on mammography. Appearance varies on the basis of breast tissue composition, with fibroglandular tissue being more dense than fatty tissue. Breast density is important because it relates to both the risk for cancer and the ability of mammography to detect cancer.

Breast density is defined and classified according to the American College of Radiology’s BI-RADS four-category scale. Categories 1 and 2 refer to breast tissue that is not dense, accounting for about 50% of the population. Categories 3 and 4 describe heterogeneously dense and extremely dense breast tissue, which occur in approximately 40% and 50% of women, respectively. When speaking about dense breast tissue readings on mammography, we are referring to categories 3 and 4.

Women with dense breast tissue have an increased risk of developing breast cancer and are less likely to have early breast cancer detected on mammography.

Let’s go over the details by category:

For women in categories 1 and 2 (considered not dense breast tissue), the sensitivity of mammography for detecting early breast cancer is 80%-90%. In categories 3 and 4, the sensitivity of mammography drops to 60%-70%.

Compared with women with average breast density, the risk of developing breast cancer is 20% higher in women with BI-RADS category 3 breasts, and more than twice as high (relative risk, 2.1) in those with BI-RADS category 4 breasts. Thus, the risk of developing breast cancer is higher, but the sensitivity of the test is lower.

Neil Skolnik, MD, is a professor, department of family medicine, at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director, department of family medicine, Abington (Pennsylvania) Jefferson Health.

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

This transcript has been edited for clarity.

Today, I’m going to talk about the 2023 Food and Drug Administration regulation that requires breast density to be reported on all mammogram results nationwide, and for that report to go to both clinicians and patients. Previously this was the rule in some states, but not in others. This is important because 40%-50% of women have dense breasts. I’m going to discuss what that means for you, and for our patients.

First I’ll review what breast density is, and how it is categorized and reported, and then why it’s important and what to do with the results.

Breast density describes the appearance of the breast on mammography. Appearance varies on the basis of breast tissue composition, with fibroglandular tissue being more dense than fatty tissue. Breast density is important because it relates to both the risk for cancer and the ability of mammography to detect cancer.

Breast density is defined and classified according to the American College of Radiology’s BI-RADS four-category scale. Categories 1 and 2 refer to breast tissue that is not dense, accounting for about 50% of the population. Categories 3 and 4 describe heterogeneously dense and extremely dense breast tissue, which occur in approximately 40% and 50% of women, respectively. When speaking about dense breast tissue readings on mammography, we are referring to categories 3 and 4.

Women with dense breast tissue have an increased risk of developing breast cancer and are less likely to have early breast cancer detected on mammography.

Let’s go over the details by category:

For women in categories 1 and 2 (considered not dense breast tissue), the sensitivity of mammography for detecting early breast cancer is 80%-90%. In categories 3 and 4, the sensitivity of mammography drops to 60%-70%.

Compared with women with average breast density, the risk of developing breast cancer is 20% higher in women with BI-RADS category 3 breasts, and more than twice as high (relative risk, 2.1) in those with BI-RADS category 4 breasts. Thus, the risk of developing breast cancer is higher, but the sensitivity of the test is lower.

Neil Skolnik, MD, is a professor, department of family medicine, at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director, department of family medicine, Abington (Pennsylvania) Jefferson Health.

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

This transcript has been edited for clarity.

Today, I’m going to talk about the 2023 Food and Drug Administration regulation that requires breast density to be reported on all mammogram results nationwide, and for that report to go to both clinicians and patients. Previously this was the rule in some states, but not in others. This is important because 40%-50% of women have dense breasts. I’m going to discuss what that means for you, and for our patients.

First I’ll review what breast density is, and how it is categorized and reported, and then why it’s important and what to do with the results.

Breast density describes the appearance of the breast on mammography. Appearance varies on the basis of breast tissue composition, with fibroglandular tissue being more dense than fatty tissue. Breast density is important because it relates to both the risk for cancer and the ability of mammography to detect cancer.

Breast density is defined and classified according to the American College of Radiology’s BI-RADS four-category scale. Categories 1 and 2 refer to breast tissue that is not dense, accounting for about 50% of the population. Categories 3 and 4 describe heterogeneously dense and extremely dense breast tissue, which occur in approximately 40% and 50% of women, respectively. When speaking about dense breast tissue readings on mammography, we are referring to categories 3 and 4.

Women with dense breast tissue have an increased risk of developing breast cancer and are less likely to have early breast cancer detected on mammography.

Let’s go over the details by category:

For women in categories 1 and 2 (considered not dense breast tissue), the sensitivity of mammography for detecting early breast cancer is 80%-90%. In categories 3 and 4, the sensitivity of mammography drops to 60%-70%.

Compared with women with average breast density, the risk of developing breast cancer is 20% higher in women with BI-RADS category 3 breasts, and more than twice as high (relative risk, 2.1) in those with BI-RADS category 4 breasts. Thus, the risk of developing breast cancer is higher, but the sensitivity of the test is lower.

Neil Skolnik, MD, is a professor, department of family medicine, at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director, department of family medicine, Abington (Pennsylvania) Jefferson Health.

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

Artificial intelligence chatbots can give accurate information to common questions about cancer but not so much when it comes to providing evidence-based cancer treatment recommendations, two new studies suggest.

AI chatbots, such as ChatGPT (OpenAI), are becoming go-to sources for health information. However, no studies have rigorously evaluated the quality of their medical advice, especially for cancer.

Two new studies published in JAMA Oncology did just that.

One, which looked at common cancer-related Google searches, found that AI chatbots generally provide accurate information to consumers, but the information’s usefulness may be limited by its complexity.

The other, which assessed cancer treatment recommendations, found that AI chatbots overall missed the mark on providing recommendations for breast, prostate, and lung cancers in line with national treatment guidelines.

The medical world is becoming “enamored with our newest potential helper, large language models (LLMs) and in particular chatbots, such as ChatGPT,” Atul Butte, MD, PhD, who heads the Bakar Computational Health Sciences Institute, University of California, San Francisco, wrote in an editorial accompanying the studies. “But maybe our core belief in GPT technology as a clinical partner has not sufficiently been earned yet.”

The first study by Alexander Pan of the State University of New York, Brooklyn, and colleagues analyzed the quality of responses to the top five most searched questions on skin, lung, breast, colorectal, and prostate cancer provided by four AI chatbots: ChatGPT-3.5, Perplexity (Perplexity.AI), Chatsonic (Writesonic), and Bing AI (Microsoft).

Questions included what is skin cancer and what are symptoms of prostate, lung, or breast cancer? The team rated the responses for quality, clarity, actionability, misinformation, and readability.

The researchers found that the four chatbots generated “high-quality” responses about the five cancers and did not appear to spread misinformation. Three of the four chatbots cited reputable sources, such as the American Cancer Society, Mayo Clinic, and Centers for Disease Controls and Prevention, which is “reassuring,” the researchers said.

However, the team also found that the usefulness of the information was “limited” because responses were often written at a college reading level. Another limitation: AI chatbots provided concise answers with no visual aids, which may not be sufficient to explain more complex ideas to consumers.

“These limitations suggest that AI chatbots should be used [supplementally] and not as a primary source for medical information,” the authors said, adding that the chatbots “typically acknowledged their limitations in providing individualized advice and encouraged users to seek medical attention.”

A related study in the journal highlighted the ability of AI chatbots to generate appropriate cancer treatment recommendations.

In this analysis, Shan Chen, MS, with the AI in Medicine Program, Mass General Brigham, Harvard Medical School, Boston, and colleagues benchmarked cancer treatment recommendations made by ChatGPT-3.5 against 2021 National Comprehensive Cancer Network guidelines.

The team created 104 prompts designed to elicit basic treatment strategies for various types of cancer, including breast, prostate, and lung cancer. Questions included “What is the treatment for stage I breast cancer?” Several oncologists then assessed the level of concordance between the chatbot responses and NCCN guidelines.

In 62% of the prompts and answers, all the recommended treatments aligned with the oncologists’ views.

The chatbot provided at least one guideline-concordant treatment for 98% of prompts. However, for 34% of prompts, the chatbot also recommended at least one nonconcordant treatment.

And about 13% of recommended treatments were “hallucinated,” that is, not part of any recommended treatment. Hallucinations were primarily recommendations for localized treatment of advanced disease, targeted therapy, or immunotherapy.

Based on the findings, the team recommended that clinicians advise patients that AI chatbots are not a reliable source of cancer treatment information.

“The chatbot did not perform well at providing accurate cancer treatment recommendations,” the authors said. “The chatbot was most likely to mix in incorrect recommendations among correct ones, an error difficult even for experts to detect.”

In his editorial, Dr. Butte highlighted several caveats, including that the teams evaluated “off the shelf” chatbots, which likely had no specific medical training, and the prompts

designed in both studies were very basic, which may have limited their specificity or actionability. Newer LLMs with specific health care training are being released, he explained.

Despite the mixed study findings, Dr. Butte remains optimistic about the future of AI in medicine.

“Today, the reality is that the highest-quality care is concentrated within a few premier medical systems like the NCI Comprehensive Cancer Centers, accessible only to a small fraction of the global population,” Dr. Butte explained. “However, AI has the potential to change this.”

How can we make this happen?

AI algorithms would need to be trained with “data from the best medical systems globally” and “the latest guidelines from NCCN and elsewhere.” Digital health platforms powered by AI could then be designed to provide resources and advice to patients around the globe, Dr. Butte said.

Although “these algorithms will need to be carefully monitored as they are brought into health systems,” Dr. Butte said, it does not change their potential to “improve care for both the haves and have-nots of health care.”

The study by Mr. Pan and colleagues had no specific funding; one author, Stacy Loeb, MD, MSc, PhD, reported a disclosure; no other disclosures were reported. The study by Shan Chen and colleagues was supported by the Woods Foundation; several authors reported disclosures outside the submitted work. Dr. Butte disclosed relationships with several pharmaceutical companies.

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

Artificial intelligence chatbots can give accurate information to common questions about cancer but not so much when it comes to providing evidence-based cancer treatment recommendations, two new studies suggest.

AI chatbots, such as ChatGPT (OpenAI), are becoming go-to sources for health information. However, no studies have rigorously evaluated the quality of their medical advice, especially for cancer.

Two new studies published in JAMA Oncology did just that.

One, which looked at common cancer-related Google searches, found that AI chatbots generally provide accurate information to consumers, but the information’s usefulness may be limited by its complexity.

The other, which assessed cancer treatment recommendations, found that AI chatbots overall missed the mark on providing recommendations for breast, prostate, and lung cancers in line with national treatment guidelines.

The medical world is becoming “enamored with our newest potential helper, large language models (LLMs) and in particular chatbots, such as ChatGPT,” Atul Butte, MD, PhD, who heads the Bakar Computational Health Sciences Institute, University of California, San Francisco, wrote in an editorial accompanying the studies. “But maybe our core belief in GPT technology as a clinical partner has not sufficiently been earned yet.”

The first study by Alexander Pan of the State University of New York, Brooklyn, and colleagues analyzed the quality of responses to the top five most searched questions on skin, lung, breast, colorectal, and prostate cancer provided by four AI chatbots: ChatGPT-3.5, Perplexity (Perplexity.AI), Chatsonic (Writesonic), and Bing AI (Microsoft).

Questions included what is skin cancer and what are symptoms of prostate, lung, or breast cancer? The team rated the responses for quality, clarity, actionability, misinformation, and readability.

The researchers found that the four chatbots generated “high-quality” responses about the five cancers and did not appear to spread misinformation. Three of the four chatbots cited reputable sources, such as the American Cancer Society, Mayo Clinic, and Centers for Disease Controls and Prevention, which is “reassuring,” the researchers said.

However, the team also found that the usefulness of the information was “limited” because responses were often written at a college reading level. Another limitation: AI chatbots provided concise answers with no visual aids, which may not be sufficient to explain more complex ideas to consumers.

“These limitations suggest that AI chatbots should be used [supplementally] and not as a primary source for medical information,” the authors said, adding that the chatbots “typically acknowledged their limitations in providing individualized advice and encouraged users to seek medical attention.”

A related study in the journal highlighted the ability of AI chatbots to generate appropriate cancer treatment recommendations.

In this analysis, Shan Chen, MS, with the AI in Medicine Program, Mass General Brigham, Harvard Medical School, Boston, and colleagues benchmarked cancer treatment recommendations made by ChatGPT-3.5 against 2021 National Comprehensive Cancer Network guidelines.

The team created 104 prompts designed to elicit basic treatment strategies for various types of cancer, including breast, prostate, and lung cancer. Questions included “What is the treatment for stage I breast cancer?” Several oncologists then assessed the level of concordance between the chatbot responses and NCCN guidelines.

In 62% of the prompts and answers, all the recommended treatments aligned with the oncologists’ views.

The chatbot provided at least one guideline-concordant treatment for 98% of prompts. However, for 34% of prompts, the chatbot also recommended at least one nonconcordant treatment.

And about 13% of recommended treatments were “hallucinated,” that is, not part of any recommended treatment. Hallucinations were primarily recommendations for localized treatment of advanced disease, targeted therapy, or immunotherapy.

Based on the findings, the team recommended that clinicians advise patients that AI chatbots are not a reliable source of cancer treatment information.

“The chatbot did not perform well at providing accurate cancer treatment recommendations,” the authors said. “The chatbot was most likely to mix in incorrect recommendations among correct ones, an error difficult even for experts to detect.”

In his editorial, Dr. Butte highlighted several caveats, including that the teams evaluated “off the shelf” chatbots, which likely had no specific medical training, and the prompts

designed in both studies were very basic, which may have limited their specificity or actionability. Newer LLMs with specific health care training are being released, he explained.

Despite the mixed study findings, Dr. Butte remains optimistic about the future of AI in medicine.

“Today, the reality is that the highest-quality care is concentrated within a few premier medical systems like the NCI Comprehensive Cancer Centers, accessible only to a small fraction of the global population,” Dr. Butte explained. “However, AI has the potential to change this.”

How can we make this happen?

AI algorithms would need to be trained with “data from the best medical systems globally” and “the latest guidelines from NCCN and elsewhere.” Digital health platforms powered by AI could then be designed to provide resources and advice to patients around the globe, Dr. Butte said.

Although “these algorithms will need to be carefully monitored as they are brought into health systems,” Dr. Butte said, it does not change their potential to “improve care for both the haves and have-nots of health care.”

The study by Mr. Pan and colleagues had no specific funding; one author, Stacy Loeb, MD, MSc, PhD, reported a disclosure; no other disclosures were reported. The study by Shan Chen and colleagues was supported by the Woods Foundation; several authors reported disclosures outside the submitted work. Dr. Butte disclosed relationships with several pharmaceutical companies.

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

Artificial intelligence chatbots can give accurate information to common questions about cancer but not so much when it comes to providing evidence-based cancer treatment recommendations, two new studies suggest.

AI chatbots, such as ChatGPT (OpenAI), are becoming go-to sources for health information. However, no studies have rigorously evaluated the quality of their medical advice, especially for cancer.

Two new studies published in JAMA Oncology did just that.

One, which looked at common cancer-related Google searches, found that AI chatbots generally provide accurate information to consumers, but the information’s usefulness may be limited by its complexity.

The other, which assessed cancer treatment recommendations, found that AI chatbots overall missed the mark on providing recommendations for breast, prostate, and lung cancers in line with national treatment guidelines.

The medical world is becoming “enamored with our newest potential helper, large language models (LLMs) and in particular chatbots, such as ChatGPT,” Atul Butte, MD, PhD, who heads the Bakar Computational Health Sciences Institute, University of California, San Francisco, wrote in an editorial accompanying the studies. “But maybe our core belief in GPT technology as a clinical partner has not sufficiently been earned yet.”

The first study by Alexander Pan of the State University of New York, Brooklyn, and colleagues analyzed the quality of responses to the top five most searched questions on skin, lung, breast, colorectal, and prostate cancer provided by four AI chatbots: ChatGPT-3.5, Perplexity (Perplexity.AI), Chatsonic (Writesonic), and Bing AI (Microsoft).

Questions included what is skin cancer and what are symptoms of prostate, lung, or breast cancer? The team rated the responses for quality, clarity, actionability, misinformation, and readability.

The researchers found that the four chatbots generated “high-quality” responses about the five cancers and did not appear to spread misinformation. Three of the four chatbots cited reputable sources, such as the American Cancer Society, Mayo Clinic, and Centers for Disease Controls and Prevention, which is “reassuring,” the researchers said.

However, the team also found that the usefulness of the information was “limited” because responses were often written at a college reading level. Another limitation: AI chatbots provided concise answers with no visual aids, which may not be sufficient to explain more complex ideas to consumers.

“These limitations suggest that AI chatbots should be used [supplementally] and not as a primary source for medical information,” the authors said, adding that the chatbots “typically acknowledged their limitations in providing individualized advice and encouraged users to seek medical attention.”

A related study in the journal highlighted the ability of AI chatbots to generate appropriate cancer treatment recommendations.

In this analysis, Shan Chen, MS, with the AI in Medicine Program, Mass General Brigham, Harvard Medical School, Boston, and colleagues benchmarked cancer treatment recommendations made by ChatGPT-3.5 against 2021 National Comprehensive Cancer Network guidelines.

The team created 104 prompts designed to elicit basic treatment strategies for various types of cancer, including breast, prostate, and lung cancer. Questions included “What is the treatment for stage I breast cancer?” Several oncologists then assessed the level of concordance between the chatbot responses and NCCN guidelines.

In 62% of the prompts and answers, all the recommended treatments aligned with the oncologists’ views.

The chatbot provided at least one guideline-concordant treatment for 98% of prompts. However, for 34% of prompts, the chatbot also recommended at least one nonconcordant treatment.

And about 13% of recommended treatments were “hallucinated,” that is, not part of any recommended treatment. Hallucinations were primarily recommendations for localized treatment of advanced disease, targeted therapy, or immunotherapy.

Based on the findings, the team recommended that clinicians advise patients that AI chatbots are not a reliable source of cancer treatment information.

“The chatbot did not perform well at providing accurate cancer treatment recommendations,” the authors said. “The chatbot was most likely to mix in incorrect recommendations among correct ones, an error difficult even for experts to detect.”

In his editorial, Dr. Butte highlighted several caveats, including that the teams evaluated “off the shelf” chatbots, which likely had no specific medical training, and the prompts

designed in both studies were very basic, which may have limited their specificity or actionability. Newer LLMs with specific health care training are being released, he explained.

Despite the mixed study findings, Dr. Butte remains optimistic about the future of AI in medicine.

“Today, the reality is that the highest-quality care is concentrated within a few premier medical systems like the NCI Comprehensive Cancer Centers, accessible only to a small fraction of the global population,” Dr. Butte explained. “However, AI has the potential to change this.”

How can we make this happen?

AI algorithms would need to be trained with “data from the best medical systems globally” and “the latest guidelines from NCCN and elsewhere.” Digital health platforms powered by AI could then be designed to provide resources and advice to patients around the globe, Dr. Butte said.

Although “these algorithms will need to be carefully monitored as they are brought into health systems,” Dr. Butte said, it does not change their potential to “improve care for both the haves and have-nots of health care.”

The study by Mr. Pan and colleagues had no specific funding; one author, Stacy Loeb, MD, MSc, PhD, reported a disclosure; no other disclosures were reported. The study by Shan Chen and colleagues was supported by the Woods Foundation; several authors reported disclosures outside the submitted work. Dr. Butte disclosed relationships with several pharmaceutical companies.

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

TOPLINE:

The Kettles Esophageal and Cardia Adenocarcinoma prediction (K-ECAN) tool predicts esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA) using data from the electronic health record (EHR) and is more accurate than other tools, a large study suggests.

METHODOLOGY:

• Researchers performed a case-control study using data from the Veterans Affairs Central Cancer Registry.
• They identified 8,430 patients with EAC and 2,965 patients GCA; these patients were compared with more than 10 million control patients.
• K-ECAN uses basic information in the EHR to determine an individual’s future risk of developing EAC or GCA.

TAKEAWAY:

• With an area under the receiver operating characteristic of 0.77, K-ECAN demonstrated better discrimination than previously validated models and published guidelines.
• Using only data from 3 to 5 years prior to diagnosis only slightly diminished its accuracy (AUROC, 0.75).
• K-ECAN remained the most accurate tool when undersampling men to simulate a non-VHA population (AUROC, 0.85).
• Although gastroesophageal reflux disease (GERD) was strongly associated with EAC, it only contributed a small proportion of gain in information for prediction.

IN PRACTICE:

Because K-ECAN does not rely heavily on GERD symptoms to assess risk, it has the “potential to guide providers to increase appropriate uptake of screening. De-emphasizing GERD in decisions to offer screening could paradoxically increase appropriate uptake of screening for EAC and GCA,” the authors wrote.

SOURCE:

The study, with first author Joel H. Rubenstein, MD, with the LTC Charles S. Kettles VA Medical Center, Ann Arbor, Mich., was published online in Gastroenterology.

LIMITATIONS:

K-ECAN was developed and validated among U.S. veterans and needs to be validated in other populations.

DISCLOSURES:

Funding for the study was provided by the Department of Defense. Dr. Rubenstein has received research support from Lucid Diagnostics.

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

TOPLINE:

The Kettles Esophageal and Cardia Adenocarcinoma prediction (K-ECAN) tool predicts esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA) using data from the electronic health record (EHR) and is more accurate than other tools, a large study suggests.

METHODOLOGY:

• Researchers performed a case-control study using data from the Veterans Affairs Central Cancer Registry.
• They identified 8,430 patients with EAC and 2,965 patients GCA; these patients were compared with more than 10 million control patients.
• K-ECAN uses basic information in the EHR to determine an individual’s future risk of developing EAC or GCA.

TAKEAWAY:

• With an area under the receiver operating characteristic of 0.77, K-ECAN demonstrated better discrimination than previously validated models and published guidelines.
• Using only data from 3 to 5 years prior to diagnosis only slightly diminished its accuracy (AUROC, 0.75).
• K-ECAN remained the most accurate tool when undersampling men to simulate a non-VHA population (AUROC, 0.85).
• Although gastroesophageal reflux disease (GERD) was strongly associated with EAC, it only contributed a small proportion of gain in information for prediction.

IN PRACTICE:

Because K-ECAN does not rely heavily on GERD symptoms to assess risk, it has the “potential to guide providers to increase appropriate uptake of screening. De-emphasizing GERD in decisions to offer screening could paradoxically increase appropriate uptake of screening for EAC and GCA,” the authors wrote.

SOURCE:

The study, with first author Joel H. Rubenstein, MD, with the LTC Charles S. Kettles VA Medical Center, Ann Arbor, Mich., was published online in Gastroenterology.

LIMITATIONS:

K-ECAN was developed and validated among U.S. veterans and needs to be validated in other populations.

DISCLOSURES:

Funding for the study was provided by the Department of Defense. Dr. Rubenstein has received research support from Lucid Diagnostics.

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

TOPLINE:

The Kettles Esophageal and Cardia Adenocarcinoma prediction (K-ECAN) tool predicts esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA) using data from the electronic health record (EHR) and is more accurate than other tools, a large study suggests.

METHODOLOGY:

• Researchers performed a case-control study using data from the Veterans Affairs Central Cancer Registry.
• They identified 8,430 patients with EAC and 2,965 patients GCA; these patients were compared with more than 10 million control patients.
• K-ECAN uses basic information in the EHR to determine an individual’s future risk of developing EAC or GCA.

TAKEAWAY:

• With an area under the receiver operating characteristic of 0.77, K-ECAN demonstrated better discrimination than previously validated models and published guidelines.
• Using only data from 3 to 5 years prior to diagnosis only slightly diminished its accuracy (AUROC, 0.75).
• K-ECAN remained the most accurate tool when undersampling men to simulate a non-VHA population (AUROC, 0.85).
• Although gastroesophageal reflux disease (GERD) was strongly associated with EAC, it only contributed a small proportion of gain in information for prediction.

IN PRACTICE:

Because K-ECAN does not rely heavily on GERD symptoms to assess risk, it has the “potential to guide providers to increase appropriate uptake of screening. De-emphasizing GERD in decisions to offer screening could paradoxically increase appropriate uptake of screening for EAC and GCA,” the authors wrote.

SOURCE:

The study, with first author Joel H. Rubenstein, MD, with the LTC Charles S. Kettles VA Medical Center, Ann Arbor, Mich., was published online in Gastroenterology.

LIMITATIONS:

K-ECAN was developed and validated among U.S. veterans and needs to be validated in other populations.

DISCLOSURES:

Funding for the study was provided by the Department of Defense. Dr. Rubenstein has received research support from Lucid Diagnostics.

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

TOPLINE:

Holding off on palliative chemotherapy until symptoms start appears to improve quality of life (QoL) without affecting survival for asymptomatic patients with advanced cancer.

METHODOLOGY:

• Traditionally, chemotherapy is started immediately when advanced cancer is diagnosed, but delaying chemotherapy until symptoms start could improve QoL.
• To find out, investigators performed a meta-analysis of five studies that explored the timing of palliative chemotherapy. The analysis included three randomized trials in advanced colorectal cancer (CRC), one in advanced ovarian cancer, and a review of patients with stage IV gastric cancer.
• Of the 919 patients, treatment was delayed for 467 patients (50.8%) until symptoms started in the colorectal trials. It was delayed until tumor recurrence in the ovarian cancer trial, and it was delayed until a month or more had passed in the gastric cancer study, regardless of symptoms.
• QoL was assessed largely by the EORTC-QLQ-C30 questionnaire. Median follow-up ranged from 11 to 60 months.

TAKEAWAY:

• The researchers found no significant differences in overall survival between patients for whom chemotherapy was delayed and those for whom chemotherapy began immediately (pooled hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.90-1.22; P = .52).
• Median overall survival was 11.9 to 25.7 months with immediate treatment, vs. 9 to 27.1 months with delayed treatment.
• In the three studies that evaluated QoL, the findings suggested that QoL was largely better among patients whose treatment was delayed. In the CRC studies that assessed QoL, for instance, global health status in the delayed treatment group was higher than that in the immediate treatment group at almost all time points, but not significantly so.
• Rates of grade 3/4 toxicities, evaluated in two studies, did not differ significantly between the groups.

IN PRACTICE:

There is limited evidence on the optimal timing for starting chemotherapy for asymptomatic patients with advanced cancer. In these studies, delaying chemotherapy until symptoms occurred did not result in worse overall survival compared with immediate treatment and may have resulted in better QoL, the researchers concluded. They noted that for asymptomatic patients, delaying the start of systemic therapy should be discussed with the patient.

SOURCE:

The study, led by Simone Augustinus of the University of Amsterdam, was published online Aug. 17 in The Oncologist.

LIMITATIONS:

• Only three types of cancer were included in the analysis, and the findings may not be generalizable to other types of cancer.
• Some of the studies were older and employed out-of-date treatment regimens.
• QoL was only evaluated in three of five studies and could not be evaluated overall in the meta-analysis because of the different time points measured in each trial.

DISCLOSURES:

The study received no external funding. Two investigators have advisory, speaker, and/or research ties to Celgene, Novartis, AstraZeneca, and other companies.

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

TOPLINE:

Holding off on palliative chemotherapy until symptoms start appears to improve quality of life (QoL) without affecting survival for asymptomatic patients with advanced cancer.

METHODOLOGY:

• Traditionally, chemotherapy is started immediately when advanced cancer is diagnosed, but delaying chemotherapy until symptoms start could improve QoL.
• To find out, investigators performed a meta-analysis of five studies that explored the timing of palliative chemotherapy. The analysis included three randomized trials in advanced colorectal cancer (CRC), one in advanced ovarian cancer, and a review of patients with stage IV gastric cancer.
• Of the 919 patients, treatment was delayed for 467 patients (50.8%) until symptoms started in the colorectal trials. It was delayed until tumor recurrence in the ovarian cancer trial, and it was delayed until a month or more had passed in the gastric cancer study, regardless of symptoms.
• QoL was assessed largely by the EORTC-QLQ-C30 questionnaire. Median follow-up ranged from 11 to 60 months.

TAKEAWAY:

• The researchers found no significant differences in overall survival between patients for whom chemotherapy was delayed and those for whom chemotherapy began immediately (pooled hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.90-1.22; P = .52).
• Median overall survival was 11.9 to 25.7 months with immediate treatment, vs. 9 to 27.1 months with delayed treatment.
• In the three studies that evaluated QoL, the findings suggested that QoL was largely better among patients whose treatment was delayed. In the CRC studies that assessed QoL, for instance, global health status in the delayed treatment group was higher than that in the immediate treatment group at almost all time points, but not significantly so.
• Rates of grade 3/4 toxicities, evaluated in two studies, did not differ significantly between the groups.

IN PRACTICE:

There is limited evidence on the optimal timing for starting chemotherapy for asymptomatic patients with advanced cancer. In these studies, delaying chemotherapy until symptoms occurred did not result in worse overall survival compared with immediate treatment and may have resulted in better QoL, the researchers concluded. They noted that for asymptomatic patients, delaying the start of systemic therapy should be discussed with the patient.

SOURCE:

The study, led by Simone Augustinus of the University of Amsterdam, was published online Aug. 17 in The Oncologist.

LIMITATIONS:

• Only three types of cancer were included in the analysis, and the findings may not be generalizable to other types of cancer.
• Some of the studies were older and employed out-of-date treatment regimens.
• QoL was only evaluated in three of five studies and could not be evaluated overall in the meta-analysis because of the different time points measured in each trial.

DISCLOSURES:

The study received no external funding. Two investigators have advisory, speaker, and/or research ties to Celgene, Novartis, AstraZeneca, and other companies.

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

TOPLINE:

Holding off on palliative chemotherapy until symptoms start appears to improve quality of life (QoL) without affecting survival for asymptomatic patients with advanced cancer.

METHODOLOGY:

• Traditionally, chemotherapy is started immediately when advanced cancer is diagnosed, but delaying chemotherapy until symptoms start could improve QoL.
• To find out, investigators performed a meta-analysis of five studies that explored the timing of palliative chemotherapy. The analysis included three randomized trials in advanced colorectal cancer (CRC), one in advanced ovarian cancer, and a review of patients with stage IV gastric cancer.
• Of the 919 patients, treatment was delayed for 467 patients (50.8%) until symptoms started in the colorectal trials. It was delayed until tumor recurrence in the ovarian cancer trial, and it was delayed until a month or more had passed in the gastric cancer study, regardless of symptoms.
• QoL was assessed largely by the EORTC-QLQ-C30 questionnaire. Median follow-up ranged from 11 to 60 months.

TAKEAWAY:

• The researchers found no significant differences in overall survival between patients for whom chemotherapy was delayed and those for whom chemotherapy began immediately (pooled hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.90-1.22; P = .52).
• Median overall survival was 11.9 to 25.7 months with immediate treatment, vs. 9 to 27.1 months with delayed treatment.
• In the three studies that evaluated QoL, the findings suggested that QoL was largely better among patients whose treatment was delayed. In the CRC studies that assessed QoL, for instance, global health status in the delayed treatment group was higher than that in the immediate treatment group at almost all time points, but not significantly so.
• Rates of grade 3/4 toxicities, evaluated in two studies, did not differ significantly between the groups.

IN PRACTICE:

There is limited evidence on the optimal timing for starting chemotherapy for asymptomatic patients with advanced cancer. In these studies, delaying chemotherapy until symptoms occurred did not result in worse overall survival compared with immediate treatment and may have resulted in better QoL, the researchers concluded. They noted that for asymptomatic patients, delaying the start of systemic therapy should be discussed with the patient.

SOURCE:

The study, led by Simone Augustinus of the University of Amsterdam, was published online Aug. 17 in The Oncologist.

LIMITATIONS:

• Only three types of cancer were included in the analysis, and the findings may not be generalizable to other types of cancer.
• Some of the studies were older and employed out-of-date treatment regimens.
• QoL was only evaluated in three of five studies and could not be evaluated overall in the meta-analysis because of the different time points measured in each trial.

DISCLOSURES:

The study received no external funding. Two investigators have advisory, speaker, and/or research ties to Celgene, Novartis, AstraZeneca, and other companies.

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

Concizumab (Novo Nordisk), a subcutaneous monoclonal antibody administered once daily, shows significant reductions in annualized bleeding rates in patients with hemophilia A or B with inhibitors, potentially representing the first subcutaneous treatment option for patients with hemophilia B with inhibitors.

“These results demonstrate the potential of concizumab as an efficacious treatment option for people living with hemophilia A or B with inhibitors – the latter a population with severely limited treatment options,” first author Tadashi Matsushita, MD, PhD, of the department of transfusion medicine, Nagoya (Japan) University Hospital, said in an interview regarding the study, published in the New England Journal of Medicine.

The results are from the prospective, multicenter, phase 3 explorer7 trial, involving 133 patients, including 80 with hemophilia A and 53 had hemophilia B, all with inhibitors, a complication of hemophilia therapy in which antibodies ‘inhibit’ clot formation and complicate standard treatment.

The patients, aged 12 or older and all receiving on-demand treatment with bypassing agents, were randomized to receive no prophylaxis for at least 24 weeks (n = 19) or concizumab prophylaxis for at least 32 weeks (n = 33), with the remaining patients nonrandomly assigned to two groups receiving concizumab prophylaxis for at least 24 weeks (n = 81).

For the primary endpoint of the estimated mean annualized bleeding rate, the rate in the no-prophylaxis group was 11.8 episodes versus just 1.7 episodes in the concizumab prophylaxis 32-week group (rate ratio, 0.14; P < .001).

The overall median annualized bleeding rate for patients in all three groups receiving concizumab was zero episodes.

Annualized rates of treated spontaneous, joint, and target joint bleeding episodes were also lower in the concizumab groups versus the no-prophylaxis group, with annualized rate ratios that were similar to the annualized rate ratio for the primary endpoint.

While similar annualized bleeding rates were observed in hemophilia subtypes, the study wasn’t powered to show superiority according the hemophilia A or B, the authors noted.

Plasma concentrations of concizumab remained stable over the course of the study.

There were no significant differences in terms of key secondary endpoints of change in bodily pain and physical functioning scores from the start of treatment to week 24.
 

Pause for safety

Treatment in the study was paused for 6 months from March 2020 to August 2020 following nonfatal thromboembolic events occurring in three patients receiving concizumab, including one in the explorer7 trial and two in the concurrent explorer8 trial, evaluating the drug in patients with hemophilia without inhibitors.

The authors wrote that the three patients had all received concomitant treatment for bleeding and had thrombotic risk factors including obesity and other comorbidities.

The trial resumed following mitigation measures that included revising the dosing regimen to include a 1–mg/kg concizumab loading dose, followed by a subcutaneous once-daily dose of 0.2 mg/kg concizumab. No further thromboembolic events were reported after the pause. Otherwise, adverse events were mainly low grade, with serious events being rare.
 

Option for hemophilia B important

Of the two disease types, hemophilia A is much more common, with an estimated prevalence in the United States of 12 cases per 100,000 males versus hemophilia B, which has a rate of only 3.7 cases per 100,000, according to the Centers for Disease Control and Prevention. Women make up only about 1% of cases with moderate to severe hemophilia.

A standard treatment of hemophilia A or B is prophylaxis with factor replacement therapies allow for improved clotting and reduced bleeding. However, one caveat is the need for intravenous injections, as often as once daily in some cases.

The development of inhibitors in response to replacement therapy may further necessitate the need for treatment with bypassing agents for breakthrough bleeding.

As an alternative, non–factor replacement therapies can promote coagulation, notably the factor VIII mimetic emicizumab, given by subcutaneous injection, and approved by the Food and Drug Administration in 2018 for patients with and without inhibitors.

Emicizumab is recommended by the World Federation on Hemophilia over bypassing agents as prophylaxis for patients with hemophilia A and persistent inhibitors.

Importantly, however, there are no effective prophylactic treatments or easily administered subcutaneous therapies available for hemophilia B with inhibitors, underscoring the potential importance of concizumab, which targets the tissue factor pathway inhibitor protein, linked to coagulation.

“Concizumab has the potential to become the first subcutaneous and first-in-class treatment for hemophilia B with inhibitors,” Dr. Matsushita said. “There are other therapies investigated for hemophilia B with and without inhibitors still in clinical development,” he noted.
 

FDA resubmission planned

In May, Novo Nordisk announced that the FDA had rejected its application for concizumab, requesting more information on the drug’s manufacturing process and its system for the monitoring and dosing of patients to ensure proper drug administration. In a statement, Novo Nordisk reported its plans to move ahead.

“Novo Nordisk has begun addressing the FDA’s feedback and is working closely with the FDA as plans for resubmission continue,” the company reported. “We are confident in the potential of concizumab to address a significant unmet need, particularly for people with hemophilia B with inhibitors who currently have limited prophylactic options and are committed to bringing this important treatment to people with hemophilia with inhibitors living in the U.S.A.”

Meanwhile in Canada, concizumab was approved in March 2023 for the treatment of adolescent and adult patients with hemophilia B with inhibitors and who require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

The authors wrote that concizumab continues to be investigated across all hemophilia subtypes, including in the explorer10 study, which is evaluating the drug in children living with hemophilia A or B, with and without inhibitors.

The study was supported by Novo Nordisk. Dr. Matsushita reported speaking for and participating on a scientific advisory board of Novo Nordisk.

Concizumab (Novo Nordisk), a subcutaneous monoclonal antibody administered once daily, shows significant reductions in annualized bleeding rates in patients with hemophilia A or B with inhibitors, potentially representing the first subcutaneous treatment option for patients with hemophilia B with inhibitors.

“These results demonstrate the potential of concizumab as an efficacious treatment option for people living with hemophilia A or B with inhibitors – the latter a population with severely limited treatment options,” first author Tadashi Matsushita, MD, PhD, of the department of transfusion medicine, Nagoya (Japan) University Hospital, said in an interview regarding the study, published in the New England Journal of Medicine.

The results are from the prospective, multicenter, phase 3 explorer7 trial, involving 133 patients, including 80 with hemophilia A and 53 had hemophilia B, all with inhibitors, a complication of hemophilia therapy in which antibodies ‘inhibit’ clot formation and complicate standard treatment.

The patients, aged 12 or older and all receiving on-demand treatment with bypassing agents, were randomized to receive no prophylaxis for at least 24 weeks (n = 19) or concizumab prophylaxis for at least 32 weeks (n = 33), with the remaining patients nonrandomly assigned to two groups receiving concizumab prophylaxis for at least 24 weeks (n = 81).

For the primary endpoint of the estimated mean annualized bleeding rate, the rate in the no-prophylaxis group was 11.8 episodes versus just 1.7 episodes in the concizumab prophylaxis 32-week group (rate ratio, 0.14; P < .001).

The overall median annualized bleeding rate for patients in all three groups receiving concizumab was zero episodes.

Annualized rates of treated spontaneous, joint, and target joint bleeding episodes were also lower in the concizumab groups versus the no-prophylaxis group, with annualized rate ratios that were similar to the annualized rate ratio for the primary endpoint.

While similar annualized bleeding rates were observed in hemophilia subtypes, the study wasn’t powered to show superiority according the hemophilia A or B, the authors noted.

Plasma concentrations of concizumab remained stable over the course of the study.

There were no significant differences in terms of key secondary endpoints of change in bodily pain and physical functioning scores from the start of treatment to week 24.
 

Pause for safety

Treatment in the study was paused for 6 months from March 2020 to August 2020 following nonfatal thromboembolic events occurring in three patients receiving concizumab, including one in the explorer7 trial and two in the concurrent explorer8 trial, evaluating the drug in patients with hemophilia without inhibitors.

The authors wrote that the three patients had all received concomitant treatment for bleeding and had thrombotic risk factors including obesity and other comorbidities.

The trial resumed following mitigation measures that included revising the dosing regimen to include a 1–mg/kg concizumab loading dose, followed by a subcutaneous once-daily dose of 0.2 mg/kg concizumab. No further thromboembolic events were reported after the pause. Otherwise, adverse events were mainly low grade, with serious events being rare.
 

Option for hemophilia B important

Of the two disease types, hemophilia A is much more common, with an estimated prevalence in the United States of 12 cases per 100,000 males versus hemophilia B, which has a rate of only 3.7 cases per 100,000, according to the Centers for Disease Control and Prevention. Women make up only about 1% of cases with moderate to severe hemophilia.

A standard treatment of hemophilia A or B is prophylaxis with factor replacement therapies allow for improved clotting and reduced bleeding. However, one caveat is the need for intravenous injections, as often as once daily in some cases.

The development of inhibitors in response to replacement therapy may further necessitate the need for treatment with bypassing agents for breakthrough bleeding.

As an alternative, non–factor replacement therapies can promote coagulation, notably the factor VIII mimetic emicizumab, given by subcutaneous injection, and approved by the Food and Drug Administration in 2018 for patients with and without inhibitors.

Emicizumab is recommended by the World Federation on Hemophilia over bypassing agents as prophylaxis for patients with hemophilia A and persistent inhibitors.

Importantly, however, there are no effective prophylactic treatments or easily administered subcutaneous therapies available for hemophilia B with inhibitors, underscoring the potential importance of concizumab, which targets the tissue factor pathway inhibitor protein, linked to coagulation.

“Concizumab has the potential to become the first subcutaneous and first-in-class treatment for hemophilia B with inhibitors,” Dr. Matsushita said. “There are other therapies investigated for hemophilia B with and without inhibitors still in clinical development,” he noted.
 

FDA resubmission planned

In May, Novo Nordisk announced that the FDA had rejected its application for concizumab, requesting more information on the drug’s manufacturing process and its system for the monitoring and dosing of patients to ensure proper drug administration. In a statement, Novo Nordisk reported its plans to move ahead.

“Novo Nordisk has begun addressing the FDA’s feedback and is working closely with the FDA as plans for resubmission continue,” the company reported. “We are confident in the potential of concizumab to address a significant unmet need, particularly for people with hemophilia B with inhibitors who currently have limited prophylactic options and are committed to bringing this important treatment to people with hemophilia with inhibitors living in the U.S.A.”

Meanwhile in Canada, concizumab was approved in March 2023 for the treatment of adolescent and adult patients with hemophilia B with inhibitors and who require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

The authors wrote that concizumab continues to be investigated across all hemophilia subtypes, including in the explorer10 study, which is evaluating the drug in children living with hemophilia A or B, with and without inhibitors.

The study was supported by Novo Nordisk. Dr. Matsushita reported speaking for and participating on a scientific advisory board of Novo Nordisk.

Concizumab (Novo Nordisk), a subcutaneous monoclonal antibody administered once daily, shows significant reductions in annualized bleeding rates in patients with hemophilia A or B with inhibitors, potentially representing the first subcutaneous treatment option for patients with hemophilia B with inhibitors.

“These results demonstrate the potential of concizumab as an efficacious treatment option for people living with hemophilia A or B with inhibitors – the latter a population with severely limited treatment options,” first author Tadashi Matsushita, MD, PhD, of the department of transfusion medicine, Nagoya (Japan) University Hospital, said in an interview regarding the study, published in the New England Journal of Medicine.

The results are from the prospective, multicenter, phase 3 explorer7 trial, involving 133 patients, including 80 with hemophilia A and 53 had hemophilia B, all with inhibitors, a complication of hemophilia therapy in which antibodies ‘inhibit’ clot formation and complicate standard treatment.

The patients, aged 12 or older and all receiving on-demand treatment with bypassing agents, were randomized to receive no prophylaxis for at least 24 weeks (n = 19) or concizumab prophylaxis for at least 32 weeks (n = 33), with the remaining patients nonrandomly assigned to two groups receiving concizumab prophylaxis for at least 24 weeks (n = 81).

For the primary endpoint of the estimated mean annualized bleeding rate, the rate in the no-prophylaxis group was 11.8 episodes versus just 1.7 episodes in the concizumab prophylaxis 32-week group (rate ratio, 0.14; P < .001).

The overall median annualized bleeding rate for patients in all three groups receiving concizumab was zero episodes.

Annualized rates of treated spontaneous, joint, and target joint bleeding episodes were also lower in the concizumab groups versus the no-prophylaxis group, with annualized rate ratios that were similar to the annualized rate ratio for the primary endpoint.

While similar annualized bleeding rates were observed in hemophilia subtypes, the study wasn’t powered to show superiority according the hemophilia A or B, the authors noted.

Plasma concentrations of concizumab remained stable over the course of the study.

There were no significant differences in terms of key secondary endpoints of change in bodily pain and physical functioning scores from the start of treatment to week 24.
 

Pause for safety

Treatment in the study was paused for 6 months from March 2020 to August 2020 following nonfatal thromboembolic events occurring in three patients receiving concizumab, including one in the explorer7 trial and two in the concurrent explorer8 trial, evaluating the drug in patients with hemophilia without inhibitors.

The authors wrote that the three patients had all received concomitant treatment for bleeding and had thrombotic risk factors including obesity and other comorbidities.

The trial resumed following mitigation measures that included revising the dosing regimen to include a 1–mg/kg concizumab loading dose, followed by a subcutaneous once-daily dose of 0.2 mg/kg concizumab. No further thromboembolic events were reported after the pause. Otherwise, adverse events were mainly low grade, with serious events being rare.
 

Option for hemophilia B important

Of the two disease types, hemophilia A is much more common, with an estimated prevalence in the United States of 12 cases per 100,000 males versus hemophilia B, which has a rate of only 3.7 cases per 100,000, according to the Centers for Disease Control and Prevention. Women make up only about 1% of cases with moderate to severe hemophilia.

A standard treatment of hemophilia A or B is prophylaxis with factor replacement therapies allow for improved clotting and reduced bleeding. However, one caveat is the need for intravenous injections, as often as once daily in some cases.

The development of inhibitors in response to replacement therapy may further necessitate the need for treatment with bypassing agents for breakthrough bleeding.

As an alternative, non–factor replacement therapies can promote coagulation, notably the factor VIII mimetic emicizumab, given by subcutaneous injection, and approved by the Food and Drug Administration in 2018 for patients with and without inhibitors.

Emicizumab is recommended by the World Federation on Hemophilia over bypassing agents as prophylaxis for patients with hemophilia A and persistent inhibitors.

Importantly, however, there are no effective prophylactic treatments or easily administered subcutaneous therapies available for hemophilia B with inhibitors, underscoring the potential importance of concizumab, which targets the tissue factor pathway inhibitor protein, linked to coagulation.

“Concizumab has the potential to become the first subcutaneous and first-in-class treatment for hemophilia B with inhibitors,” Dr. Matsushita said. “There are other therapies investigated for hemophilia B with and without inhibitors still in clinical development,” he noted.
 

FDA resubmission planned

In May, Novo Nordisk announced that the FDA had rejected its application for concizumab, requesting more information on the drug’s manufacturing process and its system for the monitoring and dosing of patients to ensure proper drug administration. In a statement, Novo Nordisk reported its plans to move ahead.

“Novo Nordisk has begun addressing the FDA’s feedback and is working closely with the FDA as plans for resubmission continue,” the company reported. “We are confident in the potential of concizumab to address a significant unmet need, particularly for people with hemophilia B with inhibitors who currently have limited prophylactic options and are committed to bringing this important treatment to people with hemophilia with inhibitors living in the U.S.A.”

Meanwhile in Canada, concizumab was approved in March 2023 for the treatment of adolescent and adult patients with hemophilia B with inhibitors and who require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

The authors wrote that concizumab continues to be investigated across all hemophilia subtypes, including in the explorer10 study, which is evaluating the drug in children living with hemophilia A or B, with and without inhibitors.

The study was supported by Novo Nordisk. Dr. Matsushita reported speaking for and participating on a scientific advisory board of Novo Nordisk.

A simple urine test can accurately diagnose urothelial carcinoma as well as predict the risk for recurrence for those under surveillance, according to findings from a recent validation study.

The urinary comprehensive genomic profiling (uCGP) assay (UroAmp, Convergent Genomics) had a specificity of 95% and sensitivity of 90% for an initial diagnosis of urothelial carcinoma in patients with hematuria – identifying 95 of 100 people with urothelial carcinoma and 90 of 100 patients without the disease.

For patients under surveillance for urothelial cancer recurrence, the test was six times more accurate than traditional clinical risk factors for predicting recurrence.

“Considering its performance in multiple areas of urothelial carcinoma diagnosis and monitoring, uCGP shows great promise to enhance delivery of risk-stratified care,” Keyan Salari, MD, PhD, director of the prostate cancer genetics program at Massachusetts General Hospital in Boston, and colleagues wrote in a study published in Clinical Cancer Research.

“The idea is that this could be used as kind of a first-pass screening tool for patients with hematuria that could potentially obviate the need for undergoing imaging such as CT scans or cystoscopy,” Dr. Salari said in an interview.

The uCGP test is a next-generation sequencing assay that identifies mutations in 60 genes associated with bladder cancer. An earlier analysis evaluating the test as a potential screening tool focused on 10 key genes covered in the assay. The study found the test accurately predicted future bladder cancer in 66% of urine samples, including some that had been collected more than a decade prior to being tested.

In the current case-control study, Dr. Salari and colleagues used a total of 581 samples – 333 samples for classifying disease and developing algorithms for initial diagnosis, surveillance, and molecular-grade prediction, as well as 248 samples for blinded validation. The test’s performance was evaluated by calculating sensitivity, specificity, positive predictive value, and negative predictive value.

Overall, the test demonstrated a specificity of 95% and sensitivity of 90% for an initial urothelial carcinoma diagnosis, but performed even better for the most aggressive tumors, with 100% sensitivity for diagnosing high-grade urothelial carcinoma and muscle-invasive tumors.

On the diagnosis front, the test had a positive predictive value of 88% and a negative predictive value of 99%.

Among patients under surveillance, the test predicted the risk of recurrence significantly better than standard clinical risk factors (hazard ratio, 6.2). The test demonstrated a positive predictive value similar to that observed for cytology (45% vs. 42%) but a much higher sensitivity (79% vs. 25%). The test also demonstrated a negative predictive value of 91% for recurrence.

The molecular-grade algorithm performed well, with a positive predictive value for high-grade disease of 88% and a specificity of 95% in the validation cohort.

Overall, “uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients,” the authors concluded. The test is not currently reimbursed by Medicare, but negotiations with third-party payers are reportedly underway.

The study was supported by the National Cancer Institute. Dr. Salari reported grants from Convergent Genomics during the conduct of the study as well as grants from Urology Care Foundation and Prostate Cancer Foundation, and personal fees from OrigiMed outside the submitted work. Several coauthors are employees and stockholders of Convergent Genomics.

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

A simple urine test can accurately diagnose urothelial carcinoma as well as predict the risk for recurrence for those under surveillance, according to findings from a recent validation study.

The urinary comprehensive genomic profiling (uCGP) assay (UroAmp, Convergent Genomics) had a specificity of 95% and sensitivity of 90% for an initial diagnosis of urothelial carcinoma in patients with hematuria – identifying 95 of 100 people with urothelial carcinoma and 90 of 100 patients without the disease.

For patients under surveillance for urothelial cancer recurrence, the test was six times more accurate than traditional clinical risk factors for predicting recurrence.

“Considering its performance in multiple areas of urothelial carcinoma diagnosis and monitoring, uCGP shows great promise to enhance delivery of risk-stratified care,” Keyan Salari, MD, PhD, director of the prostate cancer genetics program at Massachusetts General Hospital in Boston, and colleagues wrote in a study published in Clinical Cancer Research.

“The idea is that this could be used as kind of a first-pass screening tool for patients with hematuria that could potentially obviate the need for undergoing imaging such as CT scans or cystoscopy,” Dr. Salari said in an interview.

The uCGP test is a next-generation sequencing assay that identifies mutations in 60 genes associated with bladder cancer. An earlier analysis evaluating the test as a potential screening tool focused on 10 key genes covered in the assay. The study found the test accurately predicted future bladder cancer in 66% of urine samples, including some that had been collected more than a decade prior to being tested.

In the current case-control study, Dr. Salari and colleagues used a total of 581 samples – 333 samples for classifying disease and developing algorithms for initial diagnosis, surveillance, and molecular-grade prediction, as well as 248 samples for blinded validation. The test’s performance was evaluated by calculating sensitivity, specificity, positive predictive value, and negative predictive value.

Overall, the test demonstrated a specificity of 95% and sensitivity of 90% for an initial urothelial carcinoma diagnosis, but performed even better for the most aggressive tumors, with 100% sensitivity for diagnosing high-grade urothelial carcinoma and muscle-invasive tumors.

On the diagnosis front, the test had a positive predictive value of 88% and a negative predictive value of 99%.

Among patients under surveillance, the test predicted the risk of recurrence significantly better than standard clinical risk factors (hazard ratio, 6.2). The test demonstrated a positive predictive value similar to that observed for cytology (45% vs. 42%) but a much higher sensitivity (79% vs. 25%). The test also demonstrated a negative predictive value of 91% for recurrence.

The molecular-grade algorithm performed well, with a positive predictive value for high-grade disease of 88% and a specificity of 95% in the validation cohort.

Overall, “uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients,” the authors concluded. The test is not currently reimbursed by Medicare, but negotiations with third-party payers are reportedly underway.

The study was supported by the National Cancer Institute. Dr. Salari reported grants from Convergent Genomics during the conduct of the study as well as grants from Urology Care Foundation and Prostate Cancer Foundation, and personal fees from OrigiMed outside the submitted work. Several coauthors are employees and stockholders of Convergent Genomics.

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

A simple urine test can accurately diagnose urothelial carcinoma as well as predict the risk for recurrence for those under surveillance, according to findings from a recent validation study.

The urinary comprehensive genomic profiling (uCGP) assay (UroAmp, Convergent Genomics) had a specificity of 95% and sensitivity of 90% for an initial diagnosis of urothelial carcinoma in patients with hematuria – identifying 95 of 100 people with urothelial carcinoma and 90 of 100 patients without the disease.

For patients under surveillance for urothelial cancer recurrence, the test was six times more accurate than traditional clinical risk factors for predicting recurrence.

“Considering its performance in multiple areas of urothelial carcinoma diagnosis and monitoring, uCGP shows great promise to enhance delivery of risk-stratified care,” Keyan Salari, MD, PhD, director of the prostate cancer genetics program at Massachusetts General Hospital in Boston, and colleagues wrote in a study published in Clinical Cancer Research.

“The idea is that this could be used as kind of a first-pass screening tool for patients with hematuria that could potentially obviate the need for undergoing imaging such as CT scans or cystoscopy,” Dr. Salari said in an interview.

The uCGP test is a next-generation sequencing assay that identifies mutations in 60 genes associated with bladder cancer. An earlier analysis evaluating the test as a potential screening tool focused on 10 key genes covered in the assay. The study found the test accurately predicted future bladder cancer in 66% of urine samples, including some that had been collected more than a decade prior to being tested.

In the current case-control study, Dr. Salari and colleagues used a total of 581 samples – 333 samples for classifying disease and developing algorithms for initial diagnosis, surveillance, and molecular-grade prediction, as well as 248 samples for blinded validation. The test’s performance was evaluated by calculating sensitivity, specificity, positive predictive value, and negative predictive value.

Overall, the test demonstrated a specificity of 95% and sensitivity of 90% for an initial urothelial carcinoma diagnosis, but performed even better for the most aggressive tumors, with 100% sensitivity for diagnosing high-grade urothelial carcinoma and muscle-invasive tumors.

On the diagnosis front, the test had a positive predictive value of 88% and a negative predictive value of 99%.

Among patients under surveillance, the test predicted the risk of recurrence significantly better than standard clinical risk factors (hazard ratio, 6.2). The test demonstrated a positive predictive value similar to that observed for cytology (45% vs. 42%) but a much higher sensitivity (79% vs. 25%). The test also demonstrated a negative predictive value of 91% for recurrence.

The molecular-grade algorithm performed well, with a positive predictive value for high-grade disease of 88% and a specificity of 95% in the validation cohort.

Overall, “uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients,” the authors concluded. The test is not currently reimbursed by Medicare, but negotiations with third-party payers are reportedly underway.

The study was supported by the National Cancer Institute. Dr. Salari reported grants from Convergent Genomics during the conduct of the study as well as grants from Urology Care Foundation and Prostate Cancer Foundation, and personal fees from OrigiMed outside the submitted work. Several coauthors are employees and stockholders of Convergent Genomics.

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

This transcript from Impact Factor has been edited for clarity.

If you are my age or older, and like me, you are something of a rule follower, then you’re getting screened for various cancers.

Colonoscopies, mammograms, cervical cancer screening, chest CTs for people with a significant smoking history. The tests are done and usually, but not always, they are negative. And if positive, usually, but not always, follow-up tests are negative, and if they aren’t and a new cancer is diagnosed you tell yourself, Well, at least we caught it early. Isn’t it good that I’m a rule follower? My life was just saved.

But it turns out, proving that cancer screening actually saves lives is quite difficult. Is it possible that all this screening is for nothing?

The benefits, risks, or perhaps futility of cancer screening is in the news this week because of this article, appearing in JAMA Internal Medicine.

It’s a meta-analysis of very specific randomized trials of cancer screening modalities and concludes that, with the exception of sigmoidoscopy for colon cancer screening, none of them meaningfully change life expectancy.

Now – a bit of inside baseball here – I almost never choose to discuss meta-analyses on Impact Factor. It’s hard enough to dig deep into the methodology of a single study, but with a meta-analysis, you’re sort of obligated to review all the included studies, and, what’s worse, the studies that were not included but might bear on the central question.

In this case, though, the topic is important enough to think about a bit more, and the conclusions have large enough implications for public health that we should question them a bit.

First, let’s run down the study as presented.

The authors searched for randomized trials of cancer screening modalities. This is important, and I think appropriate. They wanted studies that took some people and assigned them to screening, and some people to no screening – avoiding the confounding that would come from observational data (rule followers like me tend to live longer owing to a variety of healthful behaviors, not just cancer screening).

Dr. F. Perry Wilson

JAMA Internal Medicine

Dr. F. Perry Wilson

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and his new book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

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

This transcript from Impact Factor has been edited for clarity.

If you are my age or older, and like me, you are something of a rule follower, then you’re getting screened for various cancers.

Colonoscopies, mammograms, cervical cancer screening, chest CTs for people with a significant smoking history. The tests are done and usually, but not always, they are negative. And if positive, usually, but not always, follow-up tests are negative, and if they aren’t and a new cancer is diagnosed you tell yourself, Well, at least we caught it early. Isn’t it good that I’m a rule follower? My life was just saved.

But it turns out, proving that cancer screening actually saves lives is quite difficult. Is it possible that all this screening is for nothing?

The benefits, risks, or perhaps futility of cancer screening is in the news this week because of this article, appearing in JAMA Internal Medicine.

It’s a meta-analysis of very specific randomized trials of cancer screening modalities and concludes that, with the exception of sigmoidoscopy for colon cancer screening, none of them meaningfully change life expectancy.

Now – a bit of inside baseball here – I almost never choose to discuss meta-analyses on Impact Factor. It’s hard enough to dig deep into the methodology of a single study, but with a meta-analysis, you’re sort of obligated to review all the included studies, and, what’s worse, the studies that were not included but might bear on the central question.

In this case, though, the topic is important enough to think about a bit more, and the conclusions have large enough implications for public health that we should question them a bit.

First, let’s run down the study as presented.

The authors searched for randomized trials of cancer screening modalities. This is important, and I think appropriate. They wanted studies that took some people and assigned them to screening, and some people to no screening – avoiding the confounding that would come from observational data (rule followers like me tend to live longer owing to a variety of healthful behaviors, not just cancer screening).

Dr. F. Perry Wilson

JAMA Internal Medicine

Dr. F. Perry Wilson

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and his new book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

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

This transcript from Impact Factor has been edited for clarity.

If you are my age or older, and like me, you are something of a rule follower, then you’re getting screened for various cancers.

Colonoscopies, mammograms, cervical cancer screening, chest CTs for people with a significant smoking history. The tests are done and usually, but not always, they are negative. And if positive, usually, but not always, follow-up tests are negative, and if they aren’t and a new cancer is diagnosed you tell yourself, Well, at least we caught it early. Isn’t it good that I’m a rule follower? My life was just saved.

But it turns out, proving that cancer screening actually saves lives is quite difficult. Is it possible that all this screening is for nothing?

The benefits, risks, or perhaps futility of cancer screening is in the news this week because of this article, appearing in JAMA Internal Medicine.

It’s a meta-analysis of very specific randomized trials of cancer screening modalities and concludes that, with the exception of sigmoidoscopy for colon cancer screening, none of them meaningfully change life expectancy.

Now – a bit of inside baseball here – I almost never choose to discuss meta-analyses on Impact Factor. It’s hard enough to dig deep into the methodology of a single study, but with a meta-analysis, you’re sort of obligated to review all the included studies, and, what’s worse, the studies that were not included but might bear on the central question.

In this case, though, the topic is important enough to think about a bit more, and the conclusions have large enough implications for public health that we should question them a bit.

First, let’s run down the study as presented.

The authors searched for randomized trials of cancer screening modalities. This is important, and I think appropriate. They wanted studies that took some people and assigned them to screening, and some people to no screening – avoiding the confounding that would come from observational data (rule followers like me tend to live longer owing to a variety of healthful behaviors, not just cancer screening).

Dr. F. Perry Wilson

JAMA Internal Medicine

Dr. F. Perry Wilson

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and his new book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

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

People on Medicare may in 2026 see prices drop for 10 medicines, including pricey diabetes, cancer, blood clot, and arthritis treatments, if advocates for federal drug-price negotiations can implement their plans amid tough opposition.

The Biden administration on Aug. 29 revealed the first 10 drugs selected for direct Medicare price negotiations in accordance with a process mandated by the Inflation Reduction Act of 2022.

It’s unclear at this time, though, how these negotiations will play out. The Chamber of Commerce has sided with pharmaceutical companies in bids to block direct Medicare negotiation of drug prices. Many influential Republicans in Congress oppose this plan, which has deep support from both Democrats and AARP.

While facing strong opposition to negotiations, the Centers for Medicare & Medicaid Services sought in its announcement to illustrate the high costs of the selected medicines.

CMS provided data on total Part D costs for selected medicines for the period from June 2022 to May 2023, along with tallies of the number of people taking these drugs. The 10 selected medicines are as follows:
 

• Eliquis (generic name: apixaban), used to prevent and treat serious blood clots. It is taken by about 3.7 million people through Part D plans. The estimated cost is $16.4 billion.
• Jardiance (generic name: empagliflozin), used for diabetes and heart failure. It is taken by almost 1.6 million people through Part D plans. The estimated cost is $7.06 billion.
• Xarelto (generic name: rivaroxaban), used for blood clots. It is taken by about 1.3 million people through Part D plans. The estimated cost is $6 billion.
• Januvia (generic name: sitagliptin), used for diabetes. It is taken by about 869,00 people through Part D plans. The estimated cost is $4.1 billion.
• Farxiga (generic name: dapagliflozin), used for diabetes, heart failure, and chronic kidney disease. It is taken by about 799,000 people through Part D plans. The estimated cost is almost $3.3 billion.
• Entresto (generic name: sacubitril/valsartan), used to treat heart failure. It is taken by 587,000 people through Part D plans. The estimated cost is $2.9 billion.
• Enbrel( generic name: etanercept), used for rheumatoid arthritis, psoriasis, and psoriatic arthritis. It is taken by 48,000 people through Part D plans. The estimated cost is $2.8 billion.
• Imbruvica (generic name: ibrutinib), used to treat some blood cancers. It is taken by about 20,000 people in Part D plans. The estimated cost is $2.7 billion.
• Stelara (generic name: ustekinumab), used to treat plaque psoriasis, psoriatic arthritis, or certain bowel conditions (Crohn’s disease, ulcerative colitis). It is used by about 22,000 people through Part D plans. The estimated cost is $2.6 billion.
• Fiasp; Fiasp FlexTouch; Fiasp PenFill; NovoLog; NovoLog FlexPen; NovoLog PenFill. These are forms of insulin used to treat diabetes. They are used by about 777,000 people through Part D plans. The estimated cost is $2.6 billion.

A vocal critic of Medicare drug negotiations, Joel White, president of the Council for Affordable Health Coverage, called the announcement of the 10 drugs selected for negotiation “a hollow victory lap.” A former Republican staffer on the House Ways and Means Committee, Mr. White aided with the development of the Medicare Part D plans and has kept tabs on the pharmacy programs since its launch in 2006.

“No one’s costs will go down now or for years because of this announcement” about Part D negotiations, Mr. White said in a statement.

According to its website, CAHC includes among its members the American Academy of Ophthalmology as well as some patient groups, drugmakers, such as Johnson & Johnson, and insurers and industry groups, such as the National Association of Manufacturers.

Separately, the influential Chamber of Commerce is making a strong push to at least delay the implementation of the Medicare Part D drug negotiations. On Aug. 28, the chamber released a letter sent to the Biden administration, raising concerns about a “rush” to implement the provisions of the Inflation Reduction Act.

The chamber also has filed suit to challenge the drug negotiation provisions of the Inflation Reduction Act, requesting that the court issue a preliminary injunction by Oct. 1, 2023.

Other pending legal challenges to direct Medicare drug negotiations include suits filed by Merck, Bristol-Myers Squibb, Johnson & Johnson, Boehringer Ingelheim, and AstraZeneca, according to an email from Pharmaceutical Research and Manufacturers of America. PhRMA also said it is a party to a case.

In addition, the three congressional Republicans with most direct influence over Medicare policy issued on Aug. 29 a joint statement outlining their objections to the planned negotiations on drug prices.

This drug-negotiation proposal is “an unworkable, legally dubious scheme that will lead to higher prices for new drugs coming to market, stifle the development of new cures, and destroy jobs,” said House Energy and Commerce Committee Chair Cathy McMorris Rodgers (R-Wash.), House Ways and Means Committee Chair Jason Smith (R-Mo.), and Senate Finance Committee Ranking Member Mike Crapo (R-Idaho).

Democrats were equally firm and vocal in their support of the negotiations. Senate Finance Chairman Ron Wyden (D-Ore.) issued a statement on Aug. 29 that said the release of the list of the 10 drugs selected for Medicare drug negotiations is part of a “seismic shift in the relationship between Big Pharma, the federal government, and seniors who are counting on lower prices.

“I will be following the negotiation process closely and will fight any attempt by Big Pharma to undo or undermine the progress that’s been made,” Mr. Wyden said.

In addition, AARP issued a statement of its continued support for Medicare drug negotiations.

“The No. 1 reason seniors skip or ration their prescriptions is because they can’t afford them. This must stop,” said AARP executive vice president and chief advocacy and engagement officer Nancy LeaMond in the statement. “The big drug companies and their allies continue suing to overturn the Medicare drug price negotiation program to keep up their price gouging. We can’t allow seniors to be Big Pharma’s cash machine anymore.”

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

People on Medicare may in 2026 see prices drop for 10 medicines, including pricey diabetes, cancer, blood clot, and arthritis treatments, if advocates for federal drug-price negotiations can implement their plans amid tough opposition.

The Biden administration on Aug. 29 revealed the first 10 drugs selected for direct Medicare price negotiations in accordance with a process mandated by the Inflation Reduction Act of 2022.

It’s unclear at this time, though, how these negotiations will play out. The Chamber of Commerce has sided with pharmaceutical companies in bids to block direct Medicare negotiation of drug prices. Many influential Republicans in Congress oppose this plan, which has deep support from both Democrats and AARP.

While facing strong opposition to negotiations, the Centers for Medicare & Medicaid Services sought in its announcement to illustrate the high costs of the selected medicines.

CMS provided data on total Part D costs for selected medicines for the period from June 2022 to May 2023, along with tallies of the number of people taking these drugs. The 10 selected medicines are as follows:
 

• Eliquis (generic name: apixaban), used to prevent and treat serious blood clots. It is taken by about 3.7 million people through Part D plans. The estimated cost is $16.4 billion.
• Jardiance (generic name: empagliflozin), used for diabetes and heart failure. It is taken by almost 1.6 million people through Part D plans. The estimated cost is $7.06 billion.
• Xarelto (generic name: rivaroxaban), used for blood clots. It is taken by about 1.3 million people through Part D plans. The estimated cost is $6 billion.
• Januvia (generic name: sitagliptin), used for diabetes. It is taken by about 869,00 people through Part D plans. The estimated cost is $4.1 billion.
• Farxiga (generic name: dapagliflozin), used for diabetes, heart failure, and chronic kidney disease. It is taken by about 799,000 people through Part D plans. The estimated cost is almost $3.3 billion.
• Entresto (generic name: sacubitril/valsartan), used to treat heart failure. It is taken by 587,000 people through Part D plans. The estimated cost is $2.9 billion.
• Enbrel( generic name: etanercept), used for rheumatoid arthritis, psoriasis, and psoriatic arthritis. It is taken by 48,000 people through Part D plans. The estimated cost is $2.8 billion.
• Imbruvica (generic name: ibrutinib), used to treat some blood cancers. It is taken by about 20,000 people in Part D plans. The estimated cost is $2.7 billion.
• Stelara (generic name: ustekinumab), used to treat plaque psoriasis, psoriatic arthritis, or certain bowel conditions (Crohn’s disease, ulcerative colitis). It is used by about 22,000 people through Part D plans. The estimated cost is $2.6 billion.
• Fiasp; Fiasp FlexTouch; Fiasp PenFill; NovoLog; NovoLog FlexPen; NovoLog PenFill. These are forms of insulin used to treat diabetes. They are used by about 777,000 people through Part D plans. The estimated cost is $2.6 billion.

A vocal critic of Medicare drug negotiations, Joel White, president of the Council for Affordable Health Coverage, called the announcement of the 10 drugs selected for negotiation “a hollow victory lap.” A former Republican staffer on the House Ways and Means Committee, Mr. White aided with the development of the Medicare Part D plans and has kept tabs on the pharmacy programs since its launch in 2006.

“No one’s costs will go down now or for years because of this announcement” about Part D negotiations, Mr. White said in a statement.

According to its website, CAHC includes among its members the American Academy of Ophthalmology as well as some patient groups, drugmakers, such as Johnson & Johnson, and insurers and industry groups, such as the National Association of Manufacturers.

Separately, the influential Chamber of Commerce is making a strong push to at least delay the implementation of the Medicare Part D drug negotiations. On Aug. 28, the chamber released a letter sent to the Biden administration, raising concerns about a “rush” to implement the provisions of the Inflation Reduction Act.

The chamber also has filed suit to challenge the drug negotiation provisions of the Inflation Reduction Act, requesting that the court issue a preliminary injunction by Oct. 1, 2023.

Other pending legal challenges to direct Medicare drug negotiations include suits filed by Merck, Bristol-Myers Squibb, Johnson & Johnson, Boehringer Ingelheim, and AstraZeneca, according to an email from Pharmaceutical Research and Manufacturers of America. PhRMA also said it is a party to a case.

In addition, the three congressional Republicans with most direct influence over Medicare policy issued on Aug. 29 a joint statement outlining their objections to the planned negotiations on drug prices.

This drug-negotiation proposal is “an unworkable, legally dubious scheme that will lead to higher prices for new drugs coming to market, stifle the development of new cures, and destroy jobs,” said House Energy and Commerce Committee Chair Cathy McMorris Rodgers (R-Wash.), House Ways and Means Committee Chair Jason Smith (R-Mo.), and Senate Finance Committee Ranking Member Mike Crapo (R-Idaho).

Democrats were equally firm and vocal in their support of the negotiations. Senate Finance Chairman Ron Wyden (D-Ore.) issued a statement on Aug. 29 that said the release of the list of the 10 drugs selected for Medicare drug negotiations is part of a “seismic shift in the relationship between Big Pharma, the federal government, and seniors who are counting on lower prices.

“I will be following the negotiation process closely and will fight any attempt by Big Pharma to undo or undermine the progress that’s been made,” Mr. Wyden said.

In addition, AARP issued a statement of its continued support for Medicare drug negotiations.

“The No. 1 reason seniors skip or ration their prescriptions is because they can’t afford them. This must stop,” said AARP executive vice president and chief advocacy and engagement officer Nancy LeaMond in the statement. “The big drug companies and their allies continue suing to overturn the Medicare drug price negotiation program to keep up their price gouging. We can’t allow seniors to be Big Pharma’s cash machine anymore.”

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

People on Medicare may in 2026 see prices drop for 10 medicines, including pricey diabetes, cancer, blood clot, and arthritis treatments, if advocates for federal drug-price negotiations can implement their plans amid tough opposition.

The Biden administration on Aug. 29 revealed the first 10 drugs selected for direct Medicare price negotiations in accordance with a process mandated by the Inflation Reduction Act of 2022.

It’s unclear at this time, though, how these negotiations will play out. The Chamber of Commerce has sided with pharmaceutical companies in bids to block direct Medicare negotiation of drug prices. Many influential Republicans in Congress oppose this plan, which has deep support from both Democrats and AARP.

While facing strong opposition to negotiations, the Centers for Medicare & Medicaid Services sought in its announcement to illustrate the high costs of the selected medicines.

CMS provided data on total Part D costs for selected medicines for the period from June 2022 to May 2023, along with tallies of the number of people taking these drugs. The 10 selected medicines are as follows:
 

• Eliquis (generic name: apixaban), used to prevent and treat serious blood clots. It is taken by about 3.7 million people through Part D plans. The estimated cost is $16.4 billion.
• Jardiance (generic name: empagliflozin), used for diabetes and heart failure. It is taken by almost 1.6 million people through Part D plans. The estimated cost is $7.06 billion.
• Xarelto (generic name: rivaroxaban), used for blood clots. It is taken by about 1.3 million people through Part D plans. The estimated cost is $6 billion.
• Januvia (generic name: sitagliptin), used for diabetes. It is taken by about 869,00 people through Part D plans. The estimated cost is $4.1 billion.
• Farxiga (generic name: dapagliflozin), used for diabetes, heart failure, and chronic kidney disease. It is taken by about 799,000 people through Part D plans. The estimated cost is almost $3.3 billion.
• Entresto (generic name: sacubitril/valsartan), used to treat heart failure. It is taken by 587,000 people through Part D plans. The estimated cost is $2.9 billion.
• Enbrel( generic name: etanercept), used for rheumatoid arthritis, psoriasis, and psoriatic arthritis. It is taken by 48,000 people through Part D plans. The estimated cost is $2.8 billion.
• Imbruvica (generic name: ibrutinib), used to treat some blood cancers. It is taken by about 20,000 people in Part D plans. The estimated cost is $2.7 billion.
• Stelara (generic name: ustekinumab), used to treat plaque psoriasis, psoriatic arthritis, or certain bowel conditions (Crohn’s disease, ulcerative colitis). It is used by about 22,000 people through Part D plans. The estimated cost is $2.6 billion.
• Fiasp; Fiasp FlexTouch; Fiasp PenFill; NovoLog; NovoLog FlexPen; NovoLog PenFill. These are forms of insulin used to treat diabetes. They are used by about 777,000 people through Part D plans. The estimated cost is $2.6 billion.

A vocal critic of Medicare drug negotiations, Joel White, president of the Council for Affordable Health Coverage, called the announcement of the 10 drugs selected for negotiation “a hollow victory lap.” A former Republican staffer on the House Ways and Means Committee, Mr. White aided with the development of the Medicare Part D plans and has kept tabs on the pharmacy programs since its launch in 2006.

“No one’s costs will go down now or for years because of this announcement” about Part D negotiations, Mr. White said in a statement.

According to its website, CAHC includes among its members the American Academy of Ophthalmology as well as some patient groups, drugmakers, such as Johnson & Johnson, and insurers and industry groups, such as the National Association of Manufacturers.

Separately, the influential Chamber of Commerce is making a strong push to at least delay the implementation of the Medicare Part D drug negotiations. On Aug. 28, the chamber released a letter sent to the Biden administration, raising concerns about a “rush” to implement the provisions of the Inflation Reduction Act.

The chamber also has filed suit to challenge the drug negotiation provisions of the Inflation Reduction Act, requesting that the court issue a preliminary injunction by Oct. 1, 2023.

Other pending legal challenges to direct Medicare drug negotiations include suits filed by Merck, Bristol-Myers Squibb, Johnson & Johnson, Boehringer Ingelheim, and AstraZeneca, according to an email from Pharmaceutical Research and Manufacturers of America. PhRMA also said it is a party to a case.

In addition, the three congressional Republicans with most direct influence over Medicare policy issued on Aug. 29 a joint statement outlining their objections to the planned negotiations on drug prices.

This drug-negotiation proposal is “an unworkable, legally dubious scheme that will lead to higher prices for new drugs coming to market, stifle the development of new cures, and destroy jobs,” said House Energy and Commerce Committee Chair Cathy McMorris Rodgers (R-Wash.), House Ways and Means Committee Chair Jason Smith (R-Mo.), and Senate Finance Committee Ranking Member Mike Crapo (R-Idaho).

Democrats were equally firm and vocal in their support of the negotiations. Senate Finance Chairman Ron Wyden (D-Ore.) issued a statement on Aug. 29 that said the release of the list of the 10 drugs selected for Medicare drug negotiations is part of a “seismic shift in the relationship between Big Pharma, the federal government, and seniors who are counting on lower prices.

“I will be following the negotiation process closely and will fight any attempt by Big Pharma to undo or undermine the progress that’s been made,” Mr. Wyden said.

In addition, AARP issued a statement of its continued support for Medicare drug negotiations.

“The No. 1 reason seniors skip or ration their prescriptions is because they can’t afford them. This must stop,” said AARP executive vice president and chief advocacy and engagement officer Nancy LeaMond in the statement. “The big drug companies and their allies continue suing to overturn the Medicare drug price negotiation program to keep up their price gouging. We can’t allow seniors to be Big Pharma’s cash machine anymore.”

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

Depression and anxiety were not associated with outcomes for most cancer types, including breast cancer, prostate cancer, and alcohol-related cancer, according to findings from a large, individual participant data meta-analysis.

An exception was for lung and smoking-related cancers, but key covariates appeared to explain the relationship between depression, anxiety, and these cancer types, the investigators reported.

The findings challenge a common theory that depression and anxiety increase cancer risk and should “change current thinking,” they argue.

“Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” first author Lonneke A. van Tuijl, PhD, of the University of Groningen and Utrecht University, the Netherlands, noted in a press release.

Analyses included data from up to nearly 320,000 individuals from the 18 prospective cohorts included in the international Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. The cohorts are from studies conducted in the Netherlands, United Kingdom, Norway, and Canada, and included 25,803 patients with cancer. During follow-up of up to 26 years and more than 3.2 million person-years, depression and anxiety symptoms and diagnoses showed no association with overall breast, prostate, colorectal, and alcohol-related cancers (hazard ratios, 0.98-1.05).

For the specific cancer types, the investigators “found no evidence for an association between depression or anxiety and the incidence of colorectal cancer (HRs, 0.88-1.13), prostate cancer (HRs, 0.97-1.17), or alcohol-related cancers (HRs, 0.97-1.06).”

“For breast cancer, all pooled HRs were consistently negative but mean pooled HRs were close to 1 (HRs, 0.92-0.98) and the upper limit of the 95% confidence intervals all exceeded 1 (with the exception of anxiety symptoms),” they noted.

An increase in risk observed between depression and anxiety symptoms and diagnoses and lung cancer (HRs, 1.12-1.60) and smoking-related cancers (HRs, 1.06-1.60), in minimally adjusted models, was substantially attenuated after adjusting for known risk factors such as smoking, alcohol use, and body mass index (HRs, 1.04-1.08), the investigators reported.

The findings were published online in Cancer.

“Depression and anxiety have long been hypothesized to increase the risk for cancer. It is thought that the increased cancer risk can occur via several pathways, including health behaviors, or by influencing mutation, viral oncogenes, cell proliferation, or DNA repair,” the authors explained, noting that “[c]onclusions drawn in meta-analyses vary greatly, with some supporting an association between depression, anxiety, and cancer incidence and others finding no or a negligible association.”

The current findings “may help health professionals to alleviate feelings of guilt and self-blame in patients with cancer who attribute their diagnosis to previous depression or anxiety,” they said, noting that the findings “also underscore the importance of addressing tobacco smoking and other unhealthy behaviors – including those that may develop as a result of anxiety or depression.”

“However, further research is needed to understand exactly how depression, anxiety, health behaviors, and lung cancer are related,” said Dr. Tuijl.

Dr. Tuijl has received grants and travel support from the Dutch Cancer Society (KWF).
 

Depression and anxiety were not associated with outcomes for most cancer types, including breast cancer, prostate cancer, and alcohol-related cancer, according to findings from a large, individual participant data meta-analysis.

An exception was for lung and smoking-related cancers, but key covariates appeared to explain the relationship between depression, anxiety, and these cancer types, the investigators reported.

The findings challenge a common theory that depression and anxiety increase cancer risk and should “change current thinking,” they argue.

“Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” first author Lonneke A. van Tuijl, PhD, of the University of Groningen and Utrecht University, the Netherlands, noted in a press release.

Analyses included data from up to nearly 320,000 individuals from the 18 prospective cohorts included in the international Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. The cohorts are from studies conducted in the Netherlands, United Kingdom, Norway, and Canada, and included 25,803 patients with cancer. During follow-up of up to 26 years and more than 3.2 million person-years, depression and anxiety symptoms and diagnoses showed no association with overall breast, prostate, colorectal, and alcohol-related cancers (hazard ratios, 0.98-1.05).

For the specific cancer types, the investigators “found no evidence for an association between depression or anxiety and the incidence of colorectal cancer (HRs, 0.88-1.13), prostate cancer (HRs, 0.97-1.17), or alcohol-related cancers (HRs, 0.97-1.06).”

“For breast cancer, all pooled HRs were consistently negative but mean pooled HRs were close to 1 (HRs, 0.92-0.98) and the upper limit of the 95% confidence intervals all exceeded 1 (with the exception of anxiety symptoms),” they noted.

An increase in risk observed between depression and anxiety symptoms and diagnoses and lung cancer (HRs, 1.12-1.60) and smoking-related cancers (HRs, 1.06-1.60), in minimally adjusted models, was substantially attenuated after adjusting for known risk factors such as smoking, alcohol use, and body mass index (HRs, 1.04-1.08), the investigators reported.

The findings were published online in Cancer.

“Depression and anxiety have long been hypothesized to increase the risk for cancer. It is thought that the increased cancer risk can occur via several pathways, including health behaviors, or by influencing mutation, viral oncogenes, cell proliferation, or DNA repair,” the authors explained, noting that “[c]onclusions drawn in meta-analyses vary greatly, with some supporting an association between depression, anxiety, and cancer incidence and others finding no or a negligible association.”

The current findings “may help health professionals to alleviate feelings of guilt and self-blame in patients with cancer who attribute their diagnosis to previous depression or anxiety,” they said, noting that the findings “also underscore the importance of addressing tobacco smoking and other unhealthy behaviors – including those that may develop as a result of anxiety or depression.”

“However, further research is needed to understand exactly how depression, anxiety, health behaviors, and lung cancer are related,” said Dr. Tuijl.

Dr. Tuijl has received grants and travel support from the Dutch Cancer Society (KWF).
 

Depression and anxiety were not associated with outcomes for most cancer types, including breast cancer, prostate cancer, and alcohol-related cancer, according to findings from a large, individual participant data meta-analysis.

An exception was for lung and smoking-related cancers, but key covariates appeared to explain the relationship between depression, anxiety, and these cancer types, the investigators reported.

The findings challenge a common theory that depression and anxiety increase cancer risk and should “change current thinking,” they argue.

“Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” first author Lonneke A. van Tuijl, PhD, of the University of Groningen and Utrecht University, the Netherlands, noted in a press release.

Analyses included data from up to nearly 320,000 individuals from the 18 prospective cohorts included in the international Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. The cohorts are from studies conducted in the Netherlands, United Kingdom, Norway, and Canada, and included 25,803 patients with cancer. During follow-up of up to 26 years and more than 3.2 million person-years, depression and anxiety symptoms and diagnoses showed no association with overall breast, prostate, colorectal, and alcohol-related cancers (hazard ratios, 0.98-1.05).

For the specific cancer types, the investigators “found no evidence for an association between depression or anxiety and the incidence of colorectal cancer (HRs, 0.88-1.13), prostate cancer (HRs, 0.97-1.17), or alcohol-related cancers (HRs, 0.97-1.06).”

“For breast cancer, all pooled HRs were consistently negative but mean pooled HRs were close to 1 (HRs, 0.92-0.98) and the upper limit of the 95% confidence intervals all exceeded 1 (with the exception of anxiety symptoms),” they noted.

An increase in risk observed between depression and anxiety symptoms and diagnoses and lung cancer (HRs, 1.12-1.60) and smoking-related cancers (HRs, 1.06-1.60), in minimally adjusted models, was substantially attenuated after adjusting for known risk factors such as smoking, alcohol use, and body mass index (HRs, 1.04-1.08), the investigators reported.

The findings were published online in Cancer.

“Depression and anxiety have long been hypothesized to increase the risk for cancer. It is thought that the increased cancer risk can occur via several pathways, including health behaviors, or by influencing mutation, viral oncogenes, cell proliferation, or DNA repair,” the authors explained, noting that “[c]onclusions drawn in meta-analyses vary greatly, with some supporting an association between depression, anxiety, and cancer incidence and others finding no or a negligible association.”

The current findings “may help health professionals to alleviate feelings of guilt and self-blame in patients with cancer who attribute their diagnosis to previous depression or anxiety,” they said, noting that the findings “also underscore the importance of addressing tobacco smoking and other unhealthy behaviors – including those that may develop as a result of anxiety or depression.”

“However, further research is needed to understand exactly how depression, anxiety, health behaviors, and lung cancer are related,” said Dr. Tuijl.

Dr. Tuijl has received grants and travel support from the Dutch Cancer Society (KWF).
 

Vitamin D supplementation significantly reduced the risk of relapse or death in a subgroup of patients with digestive tract cancer who were p53-immunoreactive, a recent analysis found.

In the p53-immunoreactive subgroup, daily vitamin D supplementation reduced the risk of relapse or death by 73%. Overall, the 5-year relapse-free survival (RFS) among those receiving vitamin D was 81% vs. almost 31% in the placebo group.

Vitamin D supplementation, however, had no effect on survival outcomes in the non–p53-immunoreactive subgroup.

©Kaspri/Fotolia.com

These findings represent a “game changer” for vitamin D and cancer, Michael Holick, PhD, MD, with Boston University, said in an editorial accompanying the study, published online in JAMA Network Open. The AMATERASU trial “provides an additional variable in our understanding of whether improving vitamin D status has any benefit for reducing risk of developing cancer as well as improving relapse-free and mortality outcomes.”

A growing body of research suggests that vitamin D supplementation may reduce the risk of cancer mortality, but the evidence remains mixed and efficacy may hinge on a patient’s tumor biology, specifically the p53 protein, the authors of the current analysis explained.

A 2019 randomized controlled trial from the research team found vitamin D supplements of 2000 IU/day did not improve RFS at 5 years in patients with digestive tract cancers. However, a post hoc analysis of the AMATERASU trial published in 2020 suggested that vitamin D supplementation improved RFS in a subgroup of patients with p53-positive digestive tract cancers, as seen using immunohistochemistry (IHC) staining (79% vs. 57% in the placebo group; hazard ratio, 0.52; P = .02).

In the current post hoc analysis of the AMATERASU trial, the research team explored whether vitamin D supplementation reduced the risk of relapse or death in the subgroup of patients who were p53 immunoreactive, defined as positivity for both nuclear accumulation of the p53 protein in more than 99% of cancer cells, as seen on IHC staining, as well as anti-p53 antibodies in serum.

In the trial, patients with stage I-III luminal gastrointestinal cancer who had undergone complete tumor resection were randomly assigned to receive placebo or oral vitamin D supplements of 2,000 IU/day from their first postoperative visit through the end of the trial, up to 8 years.

The current post hoc analysis by p53-immunoreactive status included 392 patients, of whom 47% had colorectal cancer, 43% had gastric cancer, 9% had esophageal cancer, and 0.5% had small-bowel cancer.

The post hoc analysis found that, among the p53-immunoreactive subgroup of 80 patients, relapse or death occurred in 9 of 54 patients (17%) in the vitamin D group and 14 of 26 patients (54%) in the placebo group. The 5-year RFS was significantly higher in the vitamin D group than the placebo group (81% vs. 31%; HR, 0.27; P = .002).

This was not the case in the 272 patients in the non–p53-immunoreactive subgroup. In this group, vitamin D supplementation had no apparent effect on 5-year RFS, compared with placebo (22% vs. 21%; HR, 1.09; 95% confidence interval, 0.65-1.84).

The main findings of this study were that daily supplementation of 2000 IU of vitamin D reduced the risk of relapse or death, compared with placebo, in the p53-immunoreactive subgroup, and they “suggest the importance of developing cancer immunotherapy targeting mutated p53 proteins,” study investigator Mitsuyoshi Urashima, MD, PhD, MPH, with Jikei University, Tokyo, and colleagues concluded.

Support for the study was provided by the Japan-Supported Program for the Strategic Research Foundation at Private Universities and a grant from the Japan Society for the Promotion of Science of the Ministry of Education, Culture, Sports, Science, and Technology. The authors report no relevant financial relationships. Dr. Holick reported grants from Carbogen Amcis and Solius; personal fees from Biogena, Sanofi, Faes Farma, Eric Anthony Nepute, and others; nonfinancial support from Ontometrics outside the submitted work; and had a patent for Novel Use of 25 hydroxy vitamin D pending for Carbogen Amcis BV and Aamanya AG.

A version of this article appeared on Medscape.com.

Vitamin D supplementation significantly reduced the risk of relapse or death in a subgroup of patients with digestive tract cancer who were p53-immunoreactive, a recent analysis found.

In the p53-immunoreactive subgroup, daily vitamin D supplementation reduced the risk of relapse or death by 73%. Overall, the 5-year relapse-free survival (RFS) among those receiving vitamin D was 81% vs. almost 31% in the placebo group.

Vitamin D supplementation, however, had no effect on survival outcomes in the non–p53-immunoreactive subgroup.

©Kaspri/Fotolia.com

These findings represent a “game changer” for vitamin D and cancer, Michael Holick, PhD, MD, with Boston University, said in an editorial accompanying the study, published online in JAMA Network Open. The AMATERASU trial “provides an additional variable in our understanding of whether improving vitamin D status has any benefit for reducing risk of developing cancer as well as improving relapse-free and mortality outcomes.”

A growing body of research suggests that vitamin D supplementation may reduce the risk of cancer mortality, but the evidence remains mixed and efficacy may hinge on a patient’s tumor biology, specifically the p53 protein, the authors of the current analysis explained.

A 2019 randomized controlled trial from the research team found vitamin D supplements of 2000 IU/day did not improve RFS at 5 years in patients with digestive tract cancers. However, a post hoc analysis of the AMATERASU trial published in 2020 suggested that vitamin D supplementation improved RFS in a subgroup of patients with p53-positive digestive tract cancers, as seen using immunohistochemistry (IHC) staining (79% vs. 57% in the placebo group; hazard ratio, 0.52; P = .02).

In the current post hoc analysis of the AMATERASU trial, the research team explored whether vitamin D supplementation reduced the risk of relapse or death in the subgroup of patients who were p53 immunoreactive, defined as positivity for both nuclear accumulation of the p53 protein in more than 99% of cancer cells, as seen on IHC staining, as well as anti-p53 antibodies in serum.

In the trial, patients with stage I-III luminal gastrointestinal cancer who had undergone complete tumor resection were randomly assigned to receive placebo or oral vitamin D supplements of 2,000 IU/day from their first postoperative visit through the end of the trial, up to 8 years.

The current post hoc analysis by p53-immunoreactive status included 392 patients, of whom 47% had colorectal cancer, 43% had gastric cancer, 9% had esophageal cancer, and 0.5% had small-bowel cancer.

The post hoc analysis found that, among the p53-immunoreactive subgroup of 80 patients, relapse or death occurred in 9 of 54 patients (17%) in the vitamin D group and 14 of 26 patients (54%) in the placebo group. The 5-year RFS was significantly higher in the vitamin D group than the placebo group (81% vs. 31%; HR, 0.27; P = .002).

This was not the case in the 272 patients in the non–p53-immunoreactive subgroup. In this group, vitamin D supplementation had no apparent effect on 5-year RFS, compared with placebo (22% vs. 21%; HR, 1.09; 95% confidence interval, 0.65-1.84).

The main findings of this study were that daily supplementation of 2000 IU of vitamin D reduced the risk of relapse or death, compared with placebo, in the p53-immunoreactive subgroup, and they “suggest the importance of developing cancer immunotherapy targeting mutated p53 proteins,” study investigator Mitsuyoshi Urashima, MD, PhD, MPH, with Jikei University, Tokyo, and colleagues concluded.

Support for the study was provided by the Japan-Supported Program for the Strategic Research Foundation at Private Universities and a grant from the Japan Society for the Promotion of Science of the Ministry of Education, Culture, Sports, Science, and Technology. The authors report no relevant financial relationships. Dr. Holick reported grants from Carbogen Amcis and Solius; personal fees from Biogena, Sanofi, Faes Farma, Eric Anthony Nepute, and others; nonfinancial support from Ontometrics outside the submitted work; and had a patent for Novel Use of 25 hydroxy vitamin D pending for Carbogen Amcis BV and Aamanya AG.

A version of this article appeared on Medscape.com.

Vitamin D supplementation significantly reduced the risk of relapse or death in a subgroup of patients with digestive tract cancer who were p53-immunoreactive, a recent analysis found.

In the p53-immunoreactive subgroup, daily vitamin D supplementation reduced the risk of relapse or death by 73%. Overall, the 5-year relapse-free survival (RFS) among those receiving vitamin D was 81% vs. almost 31% in the placebo group.

Vitamin D supplementation, however, had no effect on survival outcomes in the non–p53-immunoreactive subgroup.

©Kaspri/Fotolia.com

These findings represent a “game changer” for vitamin D and cancer, Michael Holick, PhD, MD, with Boston University, said in an editorial accompanying the study, published online in JAMA Network Open. The AMATERASU trial “provides an additional variable in our understanding of whether improving vitamin D status has any benefit for reducing risk of developing cancer as well as improving relapse-free and mortality outcomes.”

A growing body of research suggests that vitamin D supplementation may reduce the risk of cancer mortality, but the evidence remains mixed and efficacy may hinge on a patient’s tumor biology, specifically the p53 protein, the authors of the current analysis explained.

A 2019 randomized controlled trial from the research team found vitamin D supplements of 2000 IU/day did not improve RFS at 5 years in patients with digestive tract cancers. However, a post hoc analysis of the AMATERASU trial published in 2020 suggested that vitamin D supplementation improved RFS in a subgroup of patients with p53-positive digestive tract cancers, as seen using immunohistochemistry (IHC) staining (79% vs. 57% in the placebo group; hazard ratio, 0.52; P = .02).

In the current post hoc analysis of the AMATERASU trial, the research team explored whether vitamin D supplementation reduced the risk of relapse or death in the subgroup of patients who were p53 immunoreactive, defined as positivity for both nuclear accumulation of the p53 protein in more than 99% of cancer cells, as seen on IHC staining, as well as anti-p53 antibodies in serum.

In the trial, patients with stage I-III luminal gastrointestinal cancer who had undergone complete tumor resection were randomly assigned to receive placebo or oral vitamin D supplements of 2,000 IU/day from their first postoperative visit through the end of the trial, up to 8 years.

The current post hoc analysis by p53-immunoreactive status included 392 patients, of whom 47% had colorectal cancer, 43% had gastric cancer, 9% had esophageal cancer, and 0.5% had small-bowel cancer.

The post hoc analysis found that, among the p53-immunoreactive subgroup of 80 patients, relapse or death occurred in 9 of 54 patients (17%) in the vitamin D group and 14 of 26 patients (54%) in the placebo group. The 5-year RFS was significantly higher in the vitamin D group than the placebo group (81% vs. 31%; HR, 0.27; P = .002).

This was not the case in the 272 patients in the non–p53-immunoreactive subgroup. In this group, vitamin D supplementation had no apparent effect on 5-year RFS, compared with placebo (22% vs. 21%; HR, 1.09; 95% confidence interval, 0.65-1.84).

The main findings of this study were that daily supplementation of 2000 IU of vitamin D reduced the risk of relapse or death, compared with placebo, in the p53-immunoreactive subgroup, and they “suggest the importance of developing cancer immunotherapy targeting mutated p53 proteins,” study investigator Mitsuyoshi Urashima, MD, PhD, MPH, with Jikei University, Tokyo, and colleagues concluded.

Support for the study was provided by the Japan-Supported Program for the Strategic Research Foundation at Private Universities and a grant from the Japan Society for the Promotion of Science of the Ministry of Education, Culture, Sports, Science, and Technology. The authors report no relevant financial relationships. Dr. Holick reported grants from Carbogen Amcis and Solius; personal fees from Biogena, Sanofi, Faes Farma, Eric Anthony Nepute, and others; nonfinancial support from Ontometrics outside the submitted work; and had a patent for Novel Use of 25 hydroxy vitamin D pending for Carbogen Amcis BV and Aamanya AG.

A version of this article appeared on Medscape.com.