News

An AGA multidisciplinary panel has reached the conclusion that no recommendation can be made for or against the use of computer-aided detection (CADe)–assisted colonoscopy for colorectal cancer (CRC), the third most common cause of cancer mortality in the United States.

The systematic data review is a collaboration between AGA and The BMJ’s MAGIC Rapid Recommendations. The BMJ issued a separate recommendation against CADe shortly after the AGA guideline was published.

Led by Shahnaz S. Sultan, MD, MHSc, AGAF, of the Division of Gastroenterology, Hepatology, and Nutrition at University of Minnesota, Minneapolis, and recently published in Gastroenterology, found only very low certainty of GRADE-based evidence for several critical long-term outcomes, both desirable and undesirable. These included the following: 11 fewer CRCs per 10,000 individuals and two fewer CRC deaths per 10,000 individuals, an increased burden of more intensive surveillance colonoscopies (635 more per 10,000 individuals), and cost and resource implications.

This technology did, however, yield an 8% (95% CI, 6-10) absolute increase in the adenoma detection rate (ADR) and a 2% (95% CI, 0-4) increase in the detection rate of advanced adenomas and/or sessile serrated lesions. “How this translates into a reduction in CRC incidence or death is where we were uncertain,” Sultan said. “Our best effort at trying to translate the ADR and other endoscopy outcomes to CRC incidence and CRC death relied on the modeling study, which included a lot of assumptions, which also contributed to our overall lower certainty.”

The systematic and meta-analysis included 41 randomized controlled trials with more than 32,108 participants who underwent CADe-assisted colonoscopy. This technology was associated with a higher polyp detection rate than standard colonoscopy: 56.1% vs 47.9% (relative risk [RR], 1.22, 95% CI, 1.15-1.28). It also had a higher ADR: 44.8% vs 37.4% (RR, 1.22; 95% CI, 1.16-1.29).

But although CADe-assisted colonoscopy may increase ADR, it carries a risk for overdiagnosis, as most polyps detected during colonoscopy are diminutive (< 5 mm) and of low malignant potential, the panel noted. Approximately 25% of lesions are missed at colonoscopy. More than 15 million colonoscopies are performed annually in the United States, but studies have demonstrated variable quality of colonoscopies across key quality indicators.

“Artificial intelligence [AI] is revolutionizing medicine and healthcare in the field of GI [gastroenterology], and CADe in colonoscopy has been brought to commercialization,” Sultan told GI & Hepatology News. “Unlike many areas of endoscopic research where we often have a finite number of clinical trial data, CADe-assisted colonoscopy intervention has been studied in over 44 randomized controlled trials and numerous nonrandomized, real-world studies. The question of whether or not to adopt this intervention at a health system or practice level is an important question that was prioritized to be addressed as guidance was needed.”

Commenting on the guideline but not involved in its formulation, Larry S. Kim, MD, MBA, AGAF, a gastroenterologist at South Denver Gastroenterology in Denver, Colorado, said his practice group has used the GI Genius AI system in its affiliated hospitals but has so far chosen not to implement the technology at its endoscopy centers. “At the hospital, our physicians have the ability to utilize the system for select patients or not at all,” he told GI & Hepatology News.

The fact that The BMJ reached a different conclusion based on the same data, evidence-grading system, and microsimulation, Kim added, “highlights the point that when evidence for benefit is uncertain, underlying values are critical.” In declining to make a recommendation, the AGA panel balanced the benefit of improved detection of potentially precancerous adenomas vs increased resource utilization in the face of unclear benefit. “With different priorities, other bodies could reasonably decide to recommend either for or against CADe.”

 

The Future

According to Sultan, gastroenterologists need a better understanding of patient values and preferences and the value placed on increased adenoma detection, which may also lead to more lifetime colonoscopies without reducing the risk for CRC. “We need better intermediate- and long-term data on the impact of adenoma detection on interval cancers and CRC incidence,” she said. “We need data on detection of polyps that are more clinically significant such as those 6-10 mm in size, as well as serrated sessile lesions. We also need to understand at the population or health system level what the impact is on resources, cost, and access.”

Ultimately, the living guideline underscores the trade-off between desirable and undesirable effects and the limitations of current evidence to support a recommendation, but CADe has to improve as an iterative AI application with further validation and better training.

With the anticipated improvement in software accuracy as AI machine learning reads increasing numbers of images, Sultan added, “the next version of the software may perform better, especially for polyps that are more clinically significant or for flat sessile serrated polyps, which are harder to detect. We plan to revisit the question in the next year or two and potentially revise the guideline.”

These guidelines were fully funded by the AGA Institute with no funding from any outside agency or industry.

Sultan is supported by the US Food and Drug Administration. Co-authors Shazia Mehmood Siddique, Dennis L. Shung, and Benjamin Lebwohl are supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Theodore R. Levin is supported by the Permanente Medical Group Delivery Science and Applied Research Program. Cesare Hassan is a consultant for Fujifilm and Olympus. Peter S. Liang reported doing research work for Freenome and advisory board work for Guardant Health and Natera.

Kim is the AGA president-elect. He disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

An AGA multidisciplinary panel has reached the conclusion that no recommendation can be made for or against the use of computer-aided detection (CADe)–assisted colonoscopy for colorectal cancer (CRC), the third most common cause of cancer mortality in the United States.

The systematic data review is a collaboration between AGA and The BMJ’s MAGIC Rapid Recommendations. The BMJ issued a separate recommendation against CADe shortly after the AGA guideline was published.

Led by Shahnaz S. Sultan, MD, MHSc, AGAF, of the Division of Gastroenterology, Hepatology, and Nutrition at University of Minnesota, Minneapolis, and recently published in Gastroenterology, found only very low certainty of GRADE-based evidence for several critical long-term outcomes, both desirable and undesirable. These included the following: 11 fewer CRCs per 10,000 individuals and two fewer CRC deaths per 10,000 individuals, an increased burden of more intensive surveillance colonoscopies (635 more per 10,000 individuals), and cost and resource implications.

This technology did, however, yield an 8% (95% CI, 6-10) absolute increase in the adenoma detection rate (ADR) and a 2% (95% CI, 0-4) increase in the detection rate of advanced adenomas and/or sessile serrated lesions. “How this translates into a reduction in CRC incidence or death is where we were uncertain,” Sultan said. “Our best effort at trying to translate the ADR and other endoscopy outcomes to CRC incidence and CRC death relied on the modeling study, which included a lot of assumptions, which also contributed to our overall lower certainty.”

The systematic and meta-analysis included 41 randomized controlled trials with more than 32,108 participants who underwent CADe-assisted colonoscopy. This technology was associated with a higher polyp detection rate than standard colonoscopy: 56.1% vs 47.9% (relative risk [RR], 1.22, 95% CI, 1.15-1.28). It also had a higher ADR: 44.8% vs 37.4% (RR, 1.22; 95% CI, 1.16-1.29).

But although CADe-assisted colonoscopy may increase ADR, it carries a risk for overdiagnosis, as most polyps detected during colonoscopy are diminutive (< 5 mm) and of low malignant potential, the panel noted. Approximately 25% of lesions are missed at colonoscopy. More than 15 million colonoscopies are performed annually in the United States, but studies have demonstrated variable quality of colonoscopies across key quality indicators.

“Artificial intelligence [AI] is revolutionizing medicine and healthcare in the field of GI [gastroenterology], and CADe in colonoscopy has been brought to commercialization,” Sultan told GI & Hepatology News. “Unlike many areas of endoscopic research where we often have a finite number of clinical trial data, CADe-assisted colonoscopy intervention has been studied in over 44 randomized controlled trials and numerous nonrandomized, real-world studies. The question of whether or not to adopt this intervention at a health system or practice level is an important question that was prioritized to be addressed as guidance was needed.”

Commenting on the guideline but not involved in its formulation, Larry S. Kim, MD, MBA, AGAF, a gastroenterologist at South Denver Gastroenterology in Denver, Colorado, said his practice group has used the GI Genius AI system in its affiliated hospitals but has so far chosen not to implement the technology at its endoscopy centers. “At the hospital, our physicians have the ability to utilize the system for select patients or not at all,” he told GI & Hepatology News.

The fact that The BMJ reached a different conclusion based on the same data, evidence-grading system, and microsimulation, Kim added, “highlights the point that when evidence for benefit is uncertain, underlying values are critical.” In declining to make a recommendation, the AGA panel balanced the benefit of improved detection of potentially precancerous adenomas vs increased resource utilization in the face of unclear benefit. “With different priorities, other bodies could reasonably decide to recommend either for or against CADe.”

 

The Future

According to Sultan, gastroenterologists need a better understanding of patient values and preferences and the value placed on increased adenoma detection, which may also lead to more lifetime colonoscopies without reducing the risk for CRC. “We need better intermediate- and long-term data on the impact of adenoma detection on interval cancers and CRC incidence,” she said. “We need data on detection of polyps that are more clinically significant such as those 6-10 mm in size, as well as serrated sessile lesions. We also need to understand at the population or health system level what the impact is on resources, cost, and access.”

Ultimately, the living guideline underscores the trade-off between desirable and undesirable effects and the limitations of current evidence to support a recommendation, but CADe has to improve as an iterative AI application with further validation and better training.

With the anticipated improvement in software accuracy as AI machine learning reads increasing numbers of images, Sultan added, “the next version of the software may perform better, especially for polyps that are more clinically significant or for flat sessile serrated polyps, which are harder to detect. We plan to revisit the question in the next year or two and potentially revise the guideline.”

These guidelines were fully funded by the AGA Institute with no funding from any outside agency or industry.

Sultan is supported by the US Food and Drug Administration. Co-authors Shazia Mehmood Siddique, Dennis L. Shung, and Benjamin Lebwohl are supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Theodore R. Levin is supported by the Permanente Medical Group Delivery Science and Applied Research Program. Cesare Hassan is a consultant for Fujifilm and Olympus. Peter S. Liang reported doing research work for Freenome and advisory board work for Guardant Health and Natera.

Kim is the AGA president-elect. He disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

An AGA multidisciplinary panel has reached the conclusion that no recommendation can be made for or against the use of computer-aided detection (CADe)–assisted colonoscopy for colorectal cancer (CRC), the third most common cause of cancer mortality in the United States.

The systematic data review is a collaboration between AGA and The BMJ’s MAGIC Rapid Recommendations. The BMJ issued a separate recommendation against CADe shortly after the AGA guideline was published.

Led by Shahnaz S. Sultan, MD, MHSc, AGAF, of the Division of Gastroenterology, Hepatology, and Nutrition at University of Minnesota, Minneapolis, and recently published in Gastroenterology, found only very low certainty of GRADE-based evidence for several critical long-term outcomes, both desirable and undesirable. These included the following: 11 fewer CRCs per 10,000 individuals and two fewer CRC deaths per 10,000 individuals, an increased burden of more intensive surveillance colonoscopies (635 more per 10,000 individuals), and cost and resource implications.

This technology did, however, yield an 8% (95% CI, 6-10) absolute increase in the adenoma detection rate (ADR) and a 2% (95% CI, 0-4) increase in the detection rate of advanced adenomas and/or sessile serrated lesions. “How this translates into a reduction in CRC incidence or death is where we were uncertain,” Sultan said. “Our best effort at trying to translate the ADR and other endoscopy outcomes to CRC incidence and CRC death relied on the modeling study, which included a lot of assumptions, which also contributed to our overall lower certainty.”

The systematic and meta-analysis included 41 randomized controlled trials with more than 32,108 participants who underwent CADe-assisted colonoscopy. This technology was associated with a higher polyp detection rate than standard colonoscopy: 56.1% vs 47.9% (relative risk [RR], 1.22, 95% CI, 1.15-1.28). It also had a higher ADR: 44.8% vs 37.4% (RR, 1.22; 95% CI, 1.16-1.29).

But although CADe-assisted colonoscopy may increase ADR, it carries a risk for overdiagnosis, as most polyps detected during colonoscopy are diminutive (< 5 mm) and of low malignant potential, the panel noted. Approximately 25% of lesions are missed at colonoscopy. More than 15 million colonoscopies are performed annually in the United States, but studies have demonstrated variable quality of colonoscopies across key quality indicators.

“Artificial intelligence [AI] is revolutionizing medicine and healthcare in the field of GI [gastroenterology], and CADe in colonoscopy has been brought to commercialization,” Sultan told GI & Hepatology News. “Unlike many areas of endoscopic research where we often have a finite number of clinical trial data, CADe-assisted colonoscopy intervention has been studied in over 44 randomized controlled trials and numerous nonrandomized, real-world studies. The question of whether or not to adopt this intervention at a health system or practice level is an important question that was prioritized to be addressed as guidance was needed.”

Commenting on the guideline but not involved in its formulation, Larry S. Kim, MD, MBA, AGAF, a gastroenterologist at South Denver Gastroenterology in Denver, Colorado, said his practice group has used the GI Genius AI system in its affiliated hospitals but has so far chosen not to implement the technology at its endoscopy centers. “At the hospital, our physicians have the ability to utilize the system for select patients or not at all,” he told GI & Hepatology News.

The fact that The BMJ reached a different conclusion based on the same data, evidence-grading system, and microsimulation, Kim added, “highlights the point that when evidence for benefit is uncertain, underlying values are critical.” In declining to make a recommendation, the AGA panel balanced the benefit of improved detection of potentially precancerous adenomas vs increased resource utilization in the face of unclear benefit. “With different priorities, other bodies could reasonably decide to recommend either for or against CADe.”

 

The Future

According to Sultan, gastroenterologists need a better understanding of patient values and preferences and the value placed on increased adenoma detection, which may also lead to more lifetime colonoscopies without reducing the risk for CRC. “We need better intermediate- and long-term data on the impact of adenoma detection on interval cancers and CRC incidence,” she said. “We need data on detection of polyps that are more clinically significant such as those 6-10 mm in size, as well as serrated sessile lesions. We also need to understand at the population or health system level what the impact is on resources, cost, and access.”

Ultimately, the living guideline underscores the trade-off between desirable and undesirable effects and the limitations of current evidence to support a recommendation, but CADe has to improve as an iterative AI application with further validation and better training.

With the anticipated improvement in software accuracy as AI machine learning reads increasing numbers of images, Sultan added, “the next version of the software may perform better, especially for polyps that are more clinically significant or for flat sessile serrated polyps, which are harder to detect. We plan to revisit the question in the next year or two and potentially revise the guideline.”

These guidelines were fully funded by the AGA Institute with no funding from any outside agency or industry.

Sultan is supported by the US Food and Drug Administration. Co-authors Shazia Mehmood Siddique, Dennis L. Shung, and Benjamin Lebwohl are supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Theodore R. Levin is supported by the Permanente Medical Group Delivery Science and Applied Research Program. Cesare Hassan is a consultant for Fujifilm and Olympus. Peter S. Liang reported doing research work for Freenome and advisory board work for Guardant Health and Natera.

Kim is the AGA president-elect. He disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

Short-term adherence to a palatable elemental diet (PED) significantly improved symptoms and the gut microbiota in adults with microbiome-driven gastrointestinal disorders, according to a new study.

“Elemental diets have long shown promise for treating gastrointestinal disorders like Crohn’s disease, eosinophilic esophagitis, SIBO (small intestinal bacterial overgrowth), and IMO (intestinal methanogen overgrowth), but poor palatability has limited their use,” lead author Ali Rezaie, MD, medical director of the Gastrointestinal (GI) Motility Program and director of Bioinformatics at Cedars-Sinai Medical Center, Los Angeles, told GI & Hepatology News.

Elemental diets are specialized formulas tailored to meet an individual’s specific nutritional needs and daily requirements for vitamins, minerals, fat, free amino acids, and carbohydrates.

In SIBO and IMO specifically, only about half the patients respond to antibiotics, and many require repeat treatments, which underscores the need for effective nonantibiotic alternatives, said Rezaie. “This is the first prospective trial using a PED, aiming to make this approach both viable and accessible for patients,” he noted.

 

Assessing a Novel Diet in IMO and SIBO

In the study, which was recently published in Clinical Gastroenterology and Hepatology, Rezaie and colleagues enrolled 30 adults with IMO (40%), SIBO (20%), or both (40%). The mean participant age was 45 years, and 63% were women.

All participants completed 2 weeks of a PED, transitioned to 2-3 days of a bland diet, and then resumed their regular diets for 2 weeks.

The diet consisted of multiple 300-calorie packets, adjusted for individual caloric needs. Participants could consume additional packets for hunger but were prohibited from eating other foods. There was no restriction on water intake.

The primary endpoint was changes in stool microbiome after the PED and reintroduction of regular food. Secondary endpoints included lactose breath test normalization to determine bacterial overgrowth in the gut, symptom response, and adverse events.

Researchers collected 29 stool samples at baseline, 27 post-PED, and 27 at study conclusion (2 weeks post-diet).

 

Key Outcomes

Although the stool samples’ alpha diversity decreased after the PED, the difference was not statistically significant at the end of the study. However, 30 bacterial families showed significant differences in relative abundance post-PED.

Daily symptom severity improved significantly during the second week of the diet compared with baseline, with reduction in abdominal discomfort, bloating, distention, constipation, and flatulence. Further significant improvements in measures such as abdominal pain, diarrhea, fatigue, urgency, and brain fog were observed after reintroducing regular food.

“We observed 73% breath test normalization and 83% global symptom relief — with 100% adherence and tolerance to 2 weeks of exclusive PED,” Rezaie told GI & Hepatology News. No serious adverse events occurred during the study, he added.

Lactose breath test normalization rates post-PED were 58% in patients with IMO, 100% in patients with SIBO, and 75% in those with both conditions.

The extent of patient response to PED was notable, given that 83% had failed prior treatments, Rezaie said.

“While we expected benefit based on palatability improvements and prior retrospective data, the rapid reduction in methane and hydrogen gas — and the sustained microbiome modulation even after reintroducing a regular diet — exceeded expectations,” he said. A significant reduction in visceral fat was another novel finding.

“This study reinforces the power of diet as a therapeutic tool,” Rezaie said, adding that the results show that elemental diets can be palatable, thereby improving patient adherence, tolerance, and, eventually, effectiveness. This is particularly valuable for patients with SIBO and IMO who do not tolerate or respond to antibiotics, prefer nonpharmacologic options, or experience recurrent symptoms after antibiotic treatment.

 

Limitations and Next Steps

Study limitations included the lack of a placebo group with a sham diet, the short follow-up after reintroducing a regular diet, and the inability to assess microbial gene function.

However, the results support the safety, tolerance, and benefit of a PED in patients with IMO/SIBO. Personalized dietary interventions that support the growth of beneficial bacteria may be an effective approach to treating these disorders, Rezaie and colleagues noted in their publication.

Although the current study is a promising first step, longer-term studies are needed to evaluate the durability of microbiome and symptom improvements, Rezaie said.

 

Making the Most of Microbiome Manipulation

Elemental diets may help modulate the gut microbiome while reducing immune activation, making them attractive for microbiome-targeted gastrointestinal therapies, Jatin Roper, MD, a gastroenterologist at Duke University, Durham, North Carolina, told GI & Hepatology News.

“Antibiotics are only effective in half of SIBO cases and often require retreatment, so better therapies are needed,” said Roper, who was not affiliated with the study. He added that its findings confirmed the researchers’ hypothesis that a PED can be both safe and effective in patients with SIBO.

Roper noted the 83% symptom improvement as the study’s most unexpected and encouraging finding, as it represents a substantial improvement compared with standard antibiotic therapy. “It is also surprising that the tolerance rate of the elemental diet in this study was 100%,” he said.

However, diet palatability remains a major barrier in real-world practice.

“Adherence rates are likely to be far lower than in trials in which patients are closely monitored, and this challenge will not be easily overcome,” he added.

The study’s limitations, including the lack of metagenomic analysis and a placebo group, are important to address in future research, Roper said. In particular, controlled trials of elemental diets are needed to determine whether microbiome changes are directly responsible for symptom improvement.

The study was supported in part by Good LFE and the John and Geraldine Cusenza Foundation. Rezaie disclosed serving as a consultant/speaker for Bausch Health and having equity in Dieta Health, Gemelli Biotech, and Good LFE. Roper had no financial conflicts to disclose.

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

Short-term adherence to a palatable elemental diet (PED) significantly improved symptoms and the gut microbiota in adults with microbiome-driven gastrointestinal disorders, according to a new study.

“Elemental diets have long shown promise for treating gastrointestinal disorders like Crohn’s disease, eosinophilic esophagitis, SIBO (small intestinal bacterial overgrowth), and IMO (intestinal methanogen overgrowth), but poor palatability has limited their use,” lead author Ali Rezaie, MD, medical director of the Gastrointestinal (GI) Motility Program and director of Bioinformatics at Cedars-Sinai Medical Center, Los Angeles, told GI & Hepatology News.

Elemental diets are specialized formulas tailored to meet an individual’s specific nutritional needs and daily requirements for vitamins, minerals, fat, free amino acids, and carbohydrates.

In SIBO and IMO specifically, only about half the patients respond to antibiotics, and many require repeat treatments, which underscores the need for effective nonantibiotic alternatives, said Rezaie. “This is the first prospective trial using a PED, aiming to make this approach both viable and accessible for patients,” he noted.

 

Assessing a Novel Diet in IMO and SIBO

In the study, which was recently published in Clinical Gastroenterology and Hepatology, Rezaie and colleagues enrolled 30 adults with IMO (40%), SIBO (20%), or both (40%). The mean participant age was 45 years, and 63% were women.

All participants completed 2 weeks of a PED, transitioned to 2-3 days of a bland diet, and then resumed their regular diets for 2 weeks.

The diet consisted of multiple 300-calorie packets, adjusted for individual caloric needs. Participants could consume additional packets for hunger but were prohibited from eating other foods. There was no restriction on water intake.

The primary endpoint was changes in stool microbiome after the PED and reintroduction of regular food. Secondary endpoints included lactose breath test normalization to determine bacterial overgrowth in the gut, symptom response, and adverse events.

Researchers collected 29 stool samples at baseline, 27 post-PED, and 27 at study conclusion (2 weeks post-diet).

 

Key Outcomes

Although the stool samples’ alpha diversity decreased after the PED, the difference was not statistically significant at the end of the study. However, 30 bacterial families showed significant differences in relative abundance post-PED.

Daily symptom severity improved significantly during the second week of the diet compared with baseline, with reduction in abdominal discomfort, bloating, distention, constipation, and flatulence. Further significant improvements in measures such as abdominal pain, diarrhea, fatigue, urgency, and brain fog were observed after reintroducing regular food.

“We observed 73% breath test normalization and 83% global symptom relief — with 100% adherence and tolerance to 2 weeks of exclusive PED,” Rezaie told GI & Hepatology News. No serious adverse events occurred during the study, he added.

Lactose breath test normalization rates post-PED were 58% in patients with IMO, 100% in patients with SIBO, and 75% in those with both conditions.

The extent of patient response to PED was notable, given that 83% had failed prior treatments, Rezaie said.

“While we expected benefit based on palatability improvements and prior retrospective data, the rapid reduction in methane and hydrogen gas — and the sustained microbiome modulation even after reintroducing a regular diet — exceeded expectations,” he said. A significant reduction in visceral fat was another novel finding.

“This study reinforces the power of diet as a therapeutic tool,” Rezaie said, adding that the results show that elemental diets can be palatable, thereby improving patient adherence, tolerance, and, eventually, effectiveness. This is particularly valuable for patients with SIBO and IMO who do not tolerate or respond to antibiotics, prefer nonpharmacologic options, or experience recurrent symptoms after antibiotic treatment.

 

Limitations and Next Steps

Study limitations included the lack of a placebo group with a sham diet, the short follow-up after reintroducing a regular diet, and the inability to assess microbial gene function.

However, the results support the safety, tolerance, and benefit of a PED in patients with IMO/SIBO. Personalized dietary interventions that support the growth of beneficial bacteria may be an effective approach to treating these disorders, Rezaie and colleagues noted in their publication.

Although the current study is a promising first step, longer-term studies are needed to evaluate the durability of microbiome and symptom improvements, Rezaie said.

 

Making the Most of Microbiome Manipulation

Elemental diets may help modulate the gut microbiome while reducing immune activation, making them attractive for microbiome-targeted gastrointestinal therapies, Jatin Roper, MD, a gastroenterologist at Duke University, Durham, North Carolina, told GI & Hepatology News.

“Antibiotics are only effective in half of SIBO cases and often require retreatment, so better therapies are needed,” said Roper, who was not affiliated with the study. He added that its findings confirmed the researchers’ hypothesis that a PED can be both safe and effective in patients with SIBO.

Roper noted the 83% symptom improvement as the study’s most unexpected and encouraging finding, as it represents a substantial improvement compared with standard antibiotic therapy. “It is also surprising that the tolerance rate of the elemental diet in this study was 100%,” he said.

However, diet palatability remains a major barrier in real-world practice.

“Adherence rates are likely to be far lower than in trials in which patients are closely monitored, and this challenge will not be easily overcome,” he added.

The study’s limitations, including the lack of metagenomic analysis and a placebo group, are important to address in future research, Roper said. In particular, controlled trials of elemental diets are needed to determine whether microbiome changes are directly responsible for symptom improvement.

The study was supported in part by Good LFE and the John and Geraldine Cusenza Foundation. Rezaie disclosed serving as a consultant/speaker for Bausch Health and having equity in Dieta Health, Gemelli Biotech, and Good LFE. Roper had no financial conflicts to disclose.

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

Short-term adherence to a palatable elemental diet (PED) significantly improved symptoms and the gut microbiota in adults with microbiome-driven gastrointestinal disorders, according to a new study.

“Elemental diets have long shown promise for treating gastrointestinal disorders like Crohn’s disease, eosinophilic esophagitis, SIBO (small intestinal bacterial overgrowth), and IMO (intestinal methanogen overgrowth), but poor palatability has limited their use,” lead author Ali Rezaie, MD, medical director of the Gastrointestinal (GI) Motility Program and director of Bioinformatics at Cedars-Sinai Medical Center, Los Angeles, told GI & Hepatology News.

Elemental diets are specialized formulas tailored to meet an individual’s specific nutritional needs and daily requirements for vitamins, minerals, fat, free amino acids, and carbohydrates.

In SIBO and IMO specifically, only about half the patients respond to antibiotics, and many require repeat treatments, which underscores the need for effective nonantibiotic alternatives, said Rezaie. “This is the first prospective trial using a PED, aiming to make this approach both viable and accessible for patients,” he noted.

 

Assessing a Novel Diet in IMO and SIBO

In the study, which was recently published in Clinical Gastroenterology and Hepatology, Rezaie and colleagues enrolled 30 adults with IMO (40%), SIBO (20%), or both (40%). The mean participant age was 45 years, and 63% were women.

All participants completed 2 weeks of a PED, transitioned to 2-3 days of a bland diet, and then resumed their regular diets for 2 weeks.

The diet consisted of multiple 300-calorie packets, adjusted for individual caloric needs. Participants could consume additional packets for hunger but were prohibited from eating other foods. There was no restriction on water intake.

The primary endpoint was changes in stool microbiome after the PED and reintroduction of regular food. Secondary endpoints included lactose breath test normalization to determine bacterial overgrowth in the gut, symptom response, and adverse events.

Researchers collected 29 stool samples at baseline, 27 post-PED, and 27 at study conclusion (2 weeks post-diet).

 

Key Outcomes

Although the stool samples’ alpha diversity decreased after the PED, the difference was not statistically significant at the end of the study. However, 30 bacterial families showed significant differences in relative abundance post-PED.

Daily symptom severity improved significantly during the second week of the diet compared with baseline, with reduction in abdominal discomfort, bloating, distention, constipation, and flatulence. Further significant improvements in measures such as abdominal pain, diarrhea, fatigue, urgency, and brain fog were observed after reintroducing regular food.

“We observed 73% breath test normalization and 83% global symptom relief — with 100% adherence and tolerance to 2 weeks of exclusive PED,” Rezaie told GI & Hepatology News. No serious adverse events occurred during the study, he added.

Lactose breath test normalization rates post-PED were 58% in patients with IMO, 100% in patients with SIBO, and 75% in those with both conditions.

The extent of patient response to PED was notable, given that 83% had failed prior treatments, Rezaie said.

“While we expected benefit based on palatability improvements and prior retrospective data, the rapid reduction in methane and hydrogen gas — and the sustained microbiome modulation even after reintroducing a regular diet — exceeded expectations,” he said. A significant reduction in visceral fat was another novel finding.

“This study reinforces the power of diet as a therapeutic tool,” Rezaie said, adding that the results show that elemental diets can be palatable, thereby improving patient adherence, tolerance, and, eventually, effectiveness. This is particularly valuable for patients with SIBO and IMO who do not tolerate or respond to antibiotics, prefer nonpharmacologic options, or experience recurrent symptoms after antibiotic treatment.

 

Limitations and Next Steps

Study limitations included the lack of a placebo group with a sham diet, the short follow-up after reintroducing a regular diet, and the inability to assess microbial gene function.

However, the results support the safety, tolerance, and benefit of a PED in patients with IMO/SIBO. Personalized dietary interventions that support the growth of beneficial bacteria may be an effective approach to treating these disorders, Rezaie and colleagues noted in their publication.

Although the current study is a promising first step, longer-term studies are needed to evaluate the durability of microbiome and symptom improvements, Rezaie said.

 

Making the Most of Microbiome Manipulation

Elemental diets may help modulate the gut microbiome while reducing immune activation, making them attractive for microbiome-targeted gastrointestinal therapies, Jatin Roper, MD, a gastroenterologist at Duke University, Durham, North Carolina, told GI & Hepatology News.

“Antibiotics are only effective in half of SIBO cases and often require retreatment, so better therapies are needed,” said Roper, who was not affiliated with the study. He added that its findings confirmed the researchers’ hypothesis that a PED can be both safe and effective in patients with SIBO.

Roper noted the 83% symptom improvement as the study’s most unexpected and encouraging finding, as it represents a substantial improvement compared with standard antibiotic therapy. “It is also surprising that the tolerance rate of the elemental diet in this study was 100%,” he said.

However, diet palatability remains a major barrier in real-world practice.

“Adherence rates are likely to be far lower than in trials in which patients are closely monitored, and this challenge will not be easily overcome,” he added.

The study’s limitations, including the lack of metagenomic analysis and a placebo group, are important to address in future research, Roper said. In particular, controlled trials of elemental diets are needed to determine whether microbiome changes are directly responsible for symptom improvement.

The study was supported in part by Good LFE and the John and Geraldine Cusenza Foundation. Rezaie disclosed serving as a consultant/speaker for Bausch Health and having equity in Dieta Health, Gemelli Biotech, and Good LFE. Roper had no financial conflicts to disclose.

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

WASHINGTON, DC — Research on the gut microbiome — and clinical attention to it — has focused mainly on bacteria, but bacteriophages and fungi play critical roles as well, with significant influences on health and disease, experts said at the Gut Microbiota for Health (GMFH) World Summit 2025.

Fungi account for < 1% of the total genetic material in the microbiome but 1%-2% of its total biomass. “Despite their relative rarity, they have an important and outsized influence on gut health” — an impact that results from their unique interface with the immune system, said Kyla Ost, PhD, of the Anschutz Medical Campus, University of Colorado, in Denver, whose research focuses on this interface.

And bacteriophages — viruses that infect and kill bacteria — are highly abundant in the gut. “Bacteriophages begin to colonize our GI [gastrointestinal] tract at the same time we develop our own microbiome shortly after birth, and from that time on, they interact with the bacteria in our GI tract, shaping [and being shaped by] the bacterial species we carry with us,” said Robert (Chip) Schooley, MD, distinguished professor of medicine at the University of California San Diego School of Medicine.

“We’ve been talking about things that affect the gut microbiome — diet, genetics, immune response — but probably the biggest influence on what grows in the GI tract are bacteriophages,” said Schooley, co-director of the Center for Innovative Phage Applications and Therapeutics, in a session on the extra-bacterial gut ecosystem.

Among the current questions: How can phages be used to manipulate the gut microbiome and influence GI-related diseases? And how can the pathogenic potential of commensal fungi be limited?

 

‘New life’ for Phage Therapy

Bacteriophages represent a promising approach for the treatment of multidrug resistant bacterial pathogens in an era of increasing resistance and a dried-up antibiotic discovery pipeline, Schooley said. (In 2019, an estimated 4.95 million deaths around the world were associated with bacterial antimicrobial resistance, and by 2050, it has been forecast that this number will rise to an estimated 8.22 million deaths.)

But in addition to suppressing bacterial pathogens causing direct morbidity, phage therapy has the potential to suppress bacteria believed to contribute to chronic diseases, he said. “We have proof-of-concept studies about the ability of phage to modulate bacteria in the digestive tract,” and an increasing number of clinical trials of the use of phages in GI and other diseases are underway, he said.

Phages were discovered just over a century ago, but phage therapy was widely abandoned once antibiotics were developed, except for in Russia and the former Eastern Bloc countries, where phage therapy continued to be used.

Phage therapy “got new life” in the West, Schooley said, about 10-15 years ago with an increasing number of detailed and high-profile case reports, including one in which a UC San Diego colleague, Tom Patterson, PhD, contracted a deadly multidrug resistant bacterial infection in Egypt and was eventually saved with bacteriophage therapy. (The case was the subject of the book The Perfect Predator).

Since then, as described in case reports and studies in the literature, “hundreds of people have been treated with bacteriophages here and in Europe,” most commonly for pulmonary infections and infections in implanted vascular and orthopedic devices, said Schooley, who coauthored a review in Cell in 2023 that describes phage biology and advances and future directions in phage therapy.

The use of bacteriophages to prevent systemic infections during high-risk periods — such as during chemotherapeutic regimens for hematological regimens — is an area of interest, he said at the meeting.

In research that is making its way to a clinical trial of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), researchers screened a library of phages to identify those with broad coverage of Escherichia coli. Using tail fiber engineering and CRISPR technology, they then engineered a combination of the four most complementary bacteriophages to selectively kill E coli — including fluoroquinolone-resistant strains that, in patients whose GI tracts are colonized with these strains, can translocate from the gut into the bloodstream, causing sepsis, during chemotherapeutic regimens for HSCT.

In a mouse model, the CRISPR-enhanced four-phage cocktail (SNIPR001) led to a steady reduction in the E coli colony counts in stool, “showing you can modulate these bacteria in the gut by using bacteriophages to kill them,” Schooley said. Moreover, the CRISPR enhancement strengthened the phages’ ability to break up biofilms, he said, showing “that you can engineer bacteriophages to make them better killers.” A phase 1b/2a study is being planned.

 

Other Niches for Therapeutic Phages, Challenges

Bacteriophages also could be used to target a gut bacterium that has been shown to attenuate alcoholic liver disease. Patients with alcoholic hepatitis “have a gut microbiome that is different in distribution,” Schooley said, often with increased numbers of Enterococcus faecalis that produce cytolysin, an exotoxin that exacerbates liver injury and is associated with increased mortality.

In published research led by investigators at UC San Diego, stool from cytolysin-positive patients with alcoholic hepatitis was found to exacerbate ethanol-induced liver disease in gnotobiotic mice, and phage therapy against cytolytic E faecalis was found to abolish it, Schooley shared.

Research is also exploring the potential of phage therapy to selectively target adherent invasive E coli in Crohn’s disease, and Klebsiella pneumoniae in the gut microbiome as an exacerbator of inflammatory bowel disease (IBD), he said.

And investigators in Japan, he noted, have reported that bacteriophage therapy against K pneumoniae can ameliorate liver inflammation and disease severity in primary sclerosing cholangitis.

Challenges in the therapeutic use of phages include the narrow host range of phages and an uncertain predictive value of in vitro phage susceptibility testing. “We don’t know yet how to do resistance testing as well as we do with antibiotics,” he said.

In addition, most phages tend to be acid labile, requiring strategies to mitigate inactivation by gastric acid, and there are “major knowledge gaps” relating to phage pharmacology. “We also know that adaptive immune responses to phages can but often doesn’t impact therapy, and we want to understand that better in clinical trials,” Schooley said.

Phages that have a “lysogenic” lifestyle — as opposed to lytic phages which are used therapeutically — can contribute to antibiotic resistance by facilitating the interchange of bacterial resistance genes, he noted.

 

A Window Into the Mycobiome

The human gut mycobiome is primarily composed of fungi in the Saccharomyces, Candida, and Malassezia genera, with Candida species dominating. Fungal cells harbor distinct immune-stimulatory molecules and activate distinct immune pathways compared with bacteria and other members of the microbiome, said Ost, assistant professor in the immunology and microbiology department of CU Anschutz.

Some fungi, including those in the Candida genus, activate adaptive and innate immune responses that promote metabolic health and protect against infection. A recently published study in Science, for instance, demonstrated that colonization with C dubliniensis in very young mice who had been exposed to broad-spectrum antibiotics promoted “the expansion and development of beta cells in the pancreas” in a macrophage dependent manner, improving metabolic health and reducing diabetes incidence, she shared.

On the one hand, fungi can “exacerbate and perpetuate the pathogenic inflammation that’s found in a growing list of inflammatory diseases” such as IBD. And “in fact, a lot of the benefits and detriments are driven by the exact same species of fungi,” said Ost. “This is particularly true of Candida,” which is a “lifelong colonizer of intestinal microbiota that rarely causes disease but can be quite pathogenic when it does.”

A 2023 review in Nature Reviews Gastroenterology & Hepatology coauthored by Ost describes the role of commensal fungi in intestinal diseases, including IBD, colorectal cancer, and pancreatic cancer.

The pathogenic potential of commensal fungi is largely dependent on its strain, its morphology and its expression of virulence factors, researchers are learning. Ost has studied C albicans, which has been associated with intestinal inflammation and IBD. Like some other Candida species, C albicans are “fascinating shape shifters,” she said, transitioning between a less pathogenic “yeast” morphology and an elongated, adhesive “hyphae” shape that is more pathogenic.

It turns out, according to research by Ost and others, that the C albicans hyphal morphotype — and the adhesins (sticky proteins that facilitate adherence to epithelial cells) and a cytolytic toxin it produces — are preferentially targeted and suppressed by immunoglobulin A (IgA) in the gut.

“Our gut is protected by a large quantity of IgA antibodies…and these IgA interact with the microbiota and play a big role in what microbes are there and the biology of the microbes,” Ost said. Indeed, symptomatic IgA deficiency in humans has been shown to be associated with C albicans overgrowth.

Leveraging the hyphal-specific IgA response to protect against disease seems possible, she said, referring to an experimental anti-Candida fungal vaccine (NDV-3A) designed to induce an adhesin-specific immune response. In a mouse model of colitis, the vaccine protected against C albicans-associated damage. “We saw an immediate IgA response that targeted C albicans in the intestinal contents,” Ost said.

C glabrata, which has also been associated with intestinal inflammation and IBD, does not form hyphae but — depending on the strain — may also induce intestinal IgA responses, she said in describing her recent research.

Ost reported having no disclosures. Schooley disclosed being a consultant for SNIPR Biome, BiomX, Locus, MicrobiotiX, Amazon Data Monitoring Committee: Merck.

A version of this article appeared on Medscape.com.

WASHINGTON, DC — Research on the gut microbiome — and clinical attention to it — has focused mainly on bacteria, but bacteriophages and fungi play critical roles as well, with significant influences on health and disease, experts said at the Gut Microbiota for Health (GMFH) World Summit 2025.

Fungi account for < 1% of the total genetic material in the microbiome but 1%-2% of its total biomass. “Despite their relative rarity, they have an important and outsized influence on gut health” — an impact that results from their unique interface with the immune system, said Kyla Ost, PhD, of the Anschutz Medical Campus, University of Colorado, in Denver, whose research focuses on this interface.

And bacteriophages — viruses that infect and kill bacteria — are highly abundant in the gut. “Bacteriophages begin to colonize our GI [gastrointestinal] tract at the same time we develop our own microbiome shortly after birth, and from that time on, they interact with the bacteria in our GI tract, shaping [and being shaped by] the bacterial species we carry with us,” said Robert (Chip) Schooley, MD, distinguished professor of medicine at the University of California San Diego School of Medicine.

“We’ve been talking about things that affect the gut microbiome — diet, genetics, immune response — but probably the biggest influence on what grows in the GI tract are bacteriophages,” said Schooley, co-director of the Center for Innovative Phage Applications and Therapeutics, in a session on the extra-bacterial gut ecosystem.

Among the current questions: How can phages be used to manipulate the gut microbiome and influence GI-related diseases? And how can the pathogenic potential of commensal fungi be limited?

 

‘New life’ for Phage Therapy

Bacteriophages represent a promising approach for the treatment of multidrug resistant bacterial pathogens in an era of increasing resistance and a dried-up antibiotic discovery pipeline, Schooley said. (In 2019, an estimated 4.95 million deaths around the world were associated with bacterial antimicrobial resistance, and by 2050, it has been forecast that this number will rise to an estimated 8.22 million deaths.)

But in addition to suppressing bacterial pathogens causing direct morbidity, phage therapy has the potential to suppress bacteria believed to contribute to chronic diseases, he said. “We have proof-of-concept studies about the ability of phage to modulate bacteria in the digestive tract,” and an increasing number of clinical trials of the use of phages in GI and other diseases are underway, he said.

Phages were discovered just over a century ago, but phage therapy was widely abandoned once antibiotics were developed, except for in Russia and the former Eastern Bloc countries, where phage therapy continued to be used.

Phage therapy “got new life” in the West, Schooley said, about 10-15 years ago with an increasing number of detailed and high-profile case reports, including one in which a UC San Diego colleague, Tom Patterson, PhD, contracted a deadly multidrug resistant bacterial infection in Egypt and was eventually saved with bacteriophage therapy. (The case was the subject of the book The Perfect Predator).

Since then, as described in case reports and studies in the literature, “hundreds of people have been treated with bacteriophages here and in Europe,” most commonly for pulmonary infections and infections in implanted vascular and orthopedic devices, said Schooley, who coauthored a review in Cell in 2023 that describes phage biology and advances and future directions in phage therapy.

The use of bacteriophages to prevent systemic infections during high-risk periods — such as during chemotherapeutic regimens for hematological regimens — is an area of interest, he said at the meeting.

In research that is making its way to a clinical trial of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), researchers screened a library of phages to identify those with broad coverage of Escherichia coli. Using tail fiber engineering and CRISPR technology, they then engineered a combination of the four most complementary bacteriophages to selectively kill E coli — including fluoroquinolone-resistant strains that, in patients whose GI tracts are colonized with these strains, can translocate from the gut into the bloodstream, causing sepsis, during chemotherapeutic regimens for HSCT.

In a mouse model, the CRISPR-enhanced four-phage cocktail (SNIPR001) led to a steady reduction in the E coli colony counts in stool, “showing you can modulate these bacteria in the gut by using bacteriophages to kill them,” Schooley said. Moreover, the CRISPR enhancement strengthened the phages’ ability to break up biofilms, he said, showing “that you can engineer bacteriophages to make them better killers.” A phase 1b/2a study is being planned.

 

Other Niches for Therapeutic Phages, Challenges

Bacteriophages also could be used to target a gut bacterium that has been shown to attenuate alcoholic liver disease. Patients with alcoholic hepatitis “have a gut microbiome that is different in distribution,” Schooley said, often with increased numbers of Enterococcus faecalis that produce cytolysin, an exotoxin that exacerbates liver injury and is associated with increased mortality.

In published research led by investigators at UC San Diego, stool from cytolysin-positive patients with alcoholic hepatitis was found to exacerbate ethanol-induced liver disease in gnotobiotic mice, and phage therapy against cytolytic E faecalis was found to abolish it, Schooley shared.

Research is also exploring the potential of phage therapy to selectively target adherent invasive E coli in Crohn’s disease, and Klebsiella pneumoniae in the gut microbiome as an exacerbator of inflammatory bowel disease (IBD), he said.

And investigators in Japan, he noted, have reported that bacteriophage therapy against K pneumoniae can ameliorate liver inflammation and disease severity in primary sclerosing cholangitis.

Challenges in the therapeutic use of phages include the narrow host range of phages and an uncertain predictive value of in vitro phage susceptibility testing. “We don’t know yet how to do resistance testing as well as we do with antibiotics,” he said.

In addition, most phages tend to be acid labile, requiring strategies to mitigate inactivation by gastric acid, and there are “major knowledge gaps” relating to phage pharmacology. “We also know that adaptive immune responses to phages can but often doesn’t impact therapy, and we want to understand that better in clinical trials,” Schooley said.

Phages that have a “lysogenic” lifestyle — as opposed to lytic phages which are used therapeutically — can contribute to antibiotic resistance by facilitating the interchange of bacterial resistance genes, he noted.

 

A Window Into the Mycobiome

The human gut mycobiome is primarily composed of fungi in the Saccharomyces, Candida, and Malassezia genera, with Candida species dominating. Fungal cells harbor distinct immune-stimulatory molecules and activate distinct immune pathways compared with bacteria and other members of the microbiome, said Ost, assistant professor in the immunology and microbiology department of CU Anschutz.

Some fungi, including those in the Candida genus, activate adaptive and innate immune responses that promote metabolic health and protect against infection. A recently published study in Science, for instance, demonstrated that colonization with C dubliniensis in very young mice who had been exposed to broad-spectrum antibiotics promoted “the expansion and development of beta cells in the pancreas” in a macrophage dependent manner, improving metabolic health and reducing diabetes incidence, she shared.

On the one hand, fungi can “exacerbate and perpetuate the pathogenic inflammation that’s found in a growing list of inflammatory diseases” such as IBD. And “in fact, a lot of the benefits and detriments are driven by the exact same species of fungi,” said Ost. “This is particularly true of Candida,” which is a “lifelong colonizer of intestinal microbiota that rarely causes disease but can be quite pathogenic when it does.”

A 2023 review in Nature Reviews Gastroenterology & Hepatology coauthored by Ost describes the role of commensal fungi in intestinal diseases, including IBD, colorectal cancer, and pancreatic cancer.

The pathogenic potential of commensal fungi is largely dependent on its strain, its morphology and its expression of virulence factors, researchers are learning. Ost has studied C albicans, which has been associated with intestinal inflammation and IBD. Like some other Candida species, C albicans are “fascinating shape shifters,” she said, transitioning between a less pathogenic “yeast” morphology and an elongated, adhesive “hyphae” shape that is more pathogenic.

It turns out, according to research by Ost and others, that the C albicans hyphal morphotype — and the adhesins (sticky proteins that facilitate adherence to epithelial cells) and a cytolytic toxin it produces — are preferentially targeted and suppressed by immunoglobulin A (IgA) in the gut.

“Our gut is protected by a large quantity of IgA antibodies…and these IgA interact with the microbiota and play a big role in what microbes are there and the biology of the microbes,” Ost said. Indeed, symptomatic IgA deficiency in humans has been shown to be associated with C albicans overgrowth.

Leveraging the hyphal-specific IgA response to protect against disease seems possible, she said, referring to an experimental anti-Candida fungal vaccine (NDV-3A) designed to induce an adhesin-specific immune response. In a mouse model of colitis, the vaccine protected against C albicans-associated damage. “We saw an immediate IgA response that targeted C albicans in the intestinal contents,” Ost said.

C glabrata, which has also been associated with intestinal inflammation and IBD, does not form hyphae but — depending on the strain — may also induce intestinal IgA responses, she said in describing her recent research.

Ost reported having no disclosures. Schooley disclosed being a consultant for SNIPR Biome, BiomX, Locus, MicrobiotiX, Amazon Data Monitoring Committee: Merck.

A version of this article appeared on Medscape.com.

WASHINGTON, DC — Research on the gut microbiome — and clinical attention to it — has focused mainly on bacteria, but bacteriophages and fungi play critical roles as well, with significant influences on health and disease, experts said at the Gut Microbiota for Health (GMFH) World Summit 2025.

Fungi account for < 1% of the total genetic material in the microbiome but 1%-2% of its total biomass. “Despite their relative rarity, they have an important and outsized influence on gut health” — an impact that results from their unique interface with the immune system, said Kyla Ost, PhD, of the Anschutz Medical Campus, University of Colorado, in Denver, whose research focuses on this interface.

And bacteriophages — viruses that infect and kill bacteria — are highly abundant in the gut. “Bacteriophages begin to colonize our GI [gastrointestinal] tract at the same time we develop our own microbiome shortly after birth, and from that time on, they interact with the bacteria in our GI tract, shaping [and being shaped by] the bacterial species we carry with us,” said Robert (Chip) Schooley, MD, distinguished professor of medicine at the University of California San Diego School of Medicine.

“We’ve been talking about things that affect the gut microbiome — diet, genetics, immune response — but probably the biggest influence on what grows in the GI tract are bacteriophages,” said Schooley, co-director of the Center for Innovative Phage Applications and Therapeutics, in a session on the extra-bacterial gut ecosystem.

Among the current questions: How can phages be used to manipulate the gut microbiome and influence GI-related diseases? And how can the pathogenic potential of commensal fungi be limited?

 

‘New life’ for Phage Therapy

Bacteriophages represent a promising approach for the treatment of multidrug resistant bacterial pathogens in an era of increasing resistance and a dried-up antibiotic discovery pipeline, Schooley said. (In 2019, an estimated 4.95 million deaths around the world were associated with bacterial antimicrobial resistance, and by 2050, it has been forecast that this number will rise to an estimated 8.22 million deaths.)

But in addition to suppressing bacterial pathogens causing direct morbidity, phage therapy has the potential to suppress bacteria believed to contribute to chronic diseases, he said. “We have proof-of-concept studies about the ability of phage to modulate bacteria in the digestive tract,” and an increasing number of clinical trials of the use of phages in GI and other diseases are underway, he said.

Phages were discovered just over a century ago, but phage therapy was widely abandoned once antibiotics were developed, except for in Russia and the former Eastern Bloc countries, where phage therapy continued to be used.

Phage therapy “got new life” in the West, Schooley said, about 10-15 years ago with an increasing number of detailed and high-profile case reports, including one in which a UC San Diego colleague, Tom Patterson, PhD, contracted a deadly multidrug resistant bacterial infection in Egypt and was eventually saved with bacteriophage therapy. (The case was the subject of the book The Perfect Predator).

Since then, as described in case reports and studies in the literature, “hundreds of people have been treated with bacteriophages here and in Europe,” most commonly for pulmonary infections and infections in implanted vascular and orthopedic devices, said Schooley, who coauthored a review in Cell in 2023 that describes phage biology and advances and future directions in phage therapy.

The use of bacteriophages to prevent systemic infections during high-risk periods — such as during chemotherapeutic regimens for hematological regimens — is an area of interest, he said at the meeting.

In research that is making its way to a clinical trial of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), researchers screened a library of phages to identify those with broad coverage of Escherichia coli. Using tail fiber engineering and CRISPR technology, they then engineered a combination of the four most complementary bacteriophages to selectively kill E coli — including fluoroquinolone-resistant strains that, in patients whose GI tracts are colonized with these strains, can translocate from the gut into the bloodstream, causing sepsis, during chemotherapeutic regimens for HSCT.

In a mouse model, the CRISPR-enhanced four-phage cocktail (SNIPR001) led to a steady reduction in the E coli colony counts in stool, “showing you can modulate these bacteria in the gut by using bacteriophages to kill them,” Schooley said. Moreover, the CRISPR enhancement strengthened the phages’ ability to break up biofilms, he said, showing “that you can engineer bacteriophages to make them better killers.” A phase 1b/2a study is being planned.

 

Other Niches for Therapeutic Phages, Challenges

Bacteriophages also could be used to target a gut bacterium that has been shown to attenuate alcoholic liver disease. Patients with alcoholic hepatitis “have a gut microbiome that is different in distribution,” Schooley said, often with increased numbers of Enterococcus faecalis that produce cytolysin, an exotoxin that exacerbates liver injury and is associated with increased mortality.

In published research led by investigators at UC San Diego, stool from cytolysin-positive patients with alcoholic hepatitis was found to exacerbate ethanol-induced liver disease in gnotobiotic mice, and phage therapy against cytolytic E faecalis was found to abolish it, Schooley shared.

Research is also exploring the potential of phage therapy to selectively target adherent invasive E coli in Crohn’s disease, and Klebsiella pneumoniae in the gut microbiome as an exacerbator of inflammatory bowel disease (IBD), he said.

And investigators in Japan, he noted, have reported that bacteriophage therapy against K pneumoniae can ameliorate liver inflammation and disease severity in primary sclerosing cholangitis.

Challenges in the therapeutic use of phages include the narrow host range of phages and an uncertain predictive value of in vitro phage susceptibility testing. “We don’t know yet how to do resistance testing as well as we do with antibiotics,” he said.

In addition, most phages tend to be acid labile, requiring strategies to mitigate inactivation by gastric acid, and there are “major knowledge gaps” relating to phage pharmacology. “We also know that adaptive immune responses to phages can but often doesn’t impact therapy, and we want to understand that better in clinical trials,” Schooley said.

Phages that have a “lysogenic” lifestyle — as opposed to lytic phages which are used therapeutically — can contribute to antibiotic resistance by facilitating the interchange of bacterial resistance genes, he noted.

 

A Window Into the Mycobiome

The human gut mycobiome is primarily composed of fungi in the Saccharomyces, Candida, and Malassezia genera, with Candida species dominating. Fungal cells harbor distinct immune-stimulatory molecules and activate distinct immune pathways compared with bacteria and other members of the microbiome, said Ost, assistant professor in the immunology and microbiology department of CU Anschutz.

Some fungi, including those in the Candida genus, activate adaptive and innate immune responses that promote metabolic health and protect against infection. A recently published study in Science, for instance, demonstrated that colonization with C dubliniensis in very young mice who had been exposed to broad-spectrum antibiotics promoted “the expansion and development of beta cells in the pancreas” in a macrophage dependent manner, improving metabolic health and reducing diabetes incidence, she shared.

On the one hand, fungi can “exacerbate and perpetuate the pathogenic inflammation that’s found in a growing list of inflammatory diseases” such as IBD. And “in fact, a lot of the benefits and detriments are driven by the exact same species of fungi,” said Ost. “This is particularly true of Candida,” which is a “lifelong colonizer of intestinal microbiota that rarely causes disease but can be quite pathogenic when it does.”

A 2023 review in Nature Reviews Gastroenterology & Hepatology coauthored by Ost describes the role of commensal fungi in intestinal diseases, including IBD, colorectal cancer, and pancreatic cancer.

The pathogenic potential of commensal fungi is largely dependent on its strain, its morphology and its expression of virulence factors, researchers are learning. Ost has studied C albicans, which has been associated with intestinal inflammation and IBD. Like some other Candida species, C albicans are “fascinating shape shifters,” she said, transitioning between a less pathogenic “yeast” morphology and an elongated, adhesive “hyphae” shape that is more pathogenic.

It turns out, according to research by Ost and others, that the C albicans hyphal morphotype — and the adhesins (sticky proteins that facilitate adherence to epithelial cells) and a cytolytic toxin it produces — are preferentially targeted and suppressed by immunoglobulin A (IgA) in the gut.

“Our gut is protected by a large quantity of IgA antibodies…and these IgA interact with the microbiota and play a big role in what microbes are there and the biology of the microbes,” Ost said. Indeed, symptomatic IgA deficiency in humans has been shown to be associated with C albicans overgrowth.

Leveraging the hyphal-specific IgA response to protect against disease seems possible, she said, referring to an experimental anti-Candida fungal vaccine (NDV-3A) designed to induce an adhesin-specific immune response. In a mouse model of colitis, the vaccine protected against C albicans-associated damage. “We saw an immediate IgA response that targeted C albicans in the intestinal contents,” Ost said.

C glabrata, which has also been associated with intestinal inflammation and IBD, does not form hyphae but — depending on the strain — may also induce intestinal IgA responses, she said in describing her recent research.

Ost reported having no disclosures. Schooley disclosed being a consultant for SNIPR Biome, BiomX, Locus, MicrobiotiX, Amazon Data Monitoring Committee: Merck.

A version of this article appeared on Medscape.com.

A renewed effort to modernize and stabilize Medicare reimbursement for radiation therapy services is underway.

In mid-March, members of Congress reintroduced bipartisan federal legislation that would shift Medicare reimbursement for radiation oncology services from quantity-based payments to episode-based payments and help stabilize the declining rates of reimbursement in the field. 

The Radiation Oncology Case Rate (ROCR) Value Based Payment Program Act, sponsored by two senators and four representatives, would not only “transform” how Medicare reimburses radiation therapy services, it would also “protect access to high quality cancer care and improve outcomes for patients nationwide, while generating savings for Medicare,” according to a recent American Society for Radiation Oncology (ASTRO) press release praising the bill. 

However, the reaction among those in the field has been mixed. Whereas some radiation oncologists are aligned with the bill, others argue that the legislation was crafted without meaningful input from many who will be affected.

“There’s consensus across multiple groups within the house of radiation oncology, hospital groups, and industry, which is incredibly important,” according to Mustafa Basree, DO, a radiation oncology resident who serves on ASTRO’s government relations committee and was part of the discussion on drafting the bill. 

But, Basree acknowledged, “not everybody likes the bill.”

A core complaint is a lack of communication and input from clinicians in the field. “If we’re going to decide to design our own quality program — which is really like a dream from a clinician’s standpoint — we need a meaningful way to come together as a unified field,” said Matthew Spraker, MD, PhD, a radiation oncologist practicing in Denver. In this bill, “we’re not getting any of that.”

 

Impetus for the Bill

Amid dramatic drops in Medicare reimbursement — and with more probably on the horizon — ASTRO announced in January 2024 that the society had partnered with the American College of Radiation Oncology, the American College of Radiology, and the American Society of Clinical Oncology to lobby for payment reform. 

Cuts to Medicare reimbursement were approaching 25% at the time. These declines were related, in part, to changes in how radiation treatment was being delivered. Reimbursement has historically been based on the fraction of radiation given, but the field has increasingly embraced hypofractionated regimens and deescalated approaches, which have led to fewer billable fractions and consequently lower reimbursement. 

A recent study highlighted significant declines in reimbursement based on this shift in care. For instance, greater use of hypofractionation led to declines in reimbursement for technical services in freestanding radiation oncology offices by nearly 17% for breast cancer and 14.2% for prostate cancer between 2016 and 2022. Inflation-adjusted Medicare conversion factors fell 12.2% in hospital outpatient centers and 20.8% in freestanding offices.

These declining reimbursement rates have occurred alongside changes to radiation oncology practice patterns. A recent analysis reported a 51% increase in the number of US practices with at least 10 radiation oncologists between 2015 and 2023, and a 27% decrease in the number of solo practices during the same period. The number of practicing radiation oncologists increased by 16%, but the number of practices employing them decreased by 13%, indicating a trend toward practice consolidation. 

These changes, the analysis found, may affect patients’ access to care. In rural areas, retirement rates were higher and rates of entry of new radiation oncologists was lower compared with urban areas.

The current payment structure “has become untenable,” leading to practice consolidation that threaten patient access, especially in rural and underserved areas, a spokesperson for ASTRO told this news organization last year. 

 

What Is the ROCR Act?

The ROCR ACT was drafted by ASTRO to address these issues and reverse declines in Medicare reimbursement. 

In addition to shifting radiation oncology reimbursement from fraction-based to episode-based, the bill also aims to encourage clinicians to adoptevidence-based shorter treatment regimens, improve safety and quality by supporting new technologies, and generate savings to Medicare by eliminating outdated and costly practices that have not been shown to improve patient outcomes.

When first introduced last year, the bill did not receive a vote in Congress.

A 2025 version of the bill, introduced last month, largely aligns with the 2024 legislation but contains some “enhancements,” such as improving accreditation with increased incentive payments, outlining a revised exemption for practices with limited resources and instituting a transitional payment period for adaptive radiation therapy to allow billing to continue while a new code is created.

 

Mixed Reactions 

How has the radiation oncology community reacted to the latest ROCR Act? 

A recent survey, which included more than 500 practicing radiation oncologists, found that 61% of respondents supported implementing an episode-based payment model such as that proposed in the 2025 legislation, 17.3% neither supported nor opposed it, and 21.6% opposed the model.

“I think this supports this idea that our field would have benefited from much more open discussion in the design phases of the bill,” Spraker told this news organization.

Jason Beckta, MD, PhD, a radiation oncologist at Rutland Regional Medical Center, Vermont, agreed. 

While on board with the concept of reform and episode-based payment, given what Beckta called “the absolute absurdity of the cuts in radiation oncology,” he took issue with the lack of transparency in the rollout of the bill.

The announcement about the 2025 version of the ROCR Act came as “a complete surprise — out of nowhere — except to insiders,” Beckta said.

ASTRO held a town hall in February 2025 “featuring new information and discussion” regarding ROCR 2025, but the bill had already been finalized for submission at that point, Beckta said. 

And although Beckta and Spraker believe ASTRO had good intentions, the physicians highlighted concerns with several aspects of the bill.

“What upsets me most is the blatant regulatory capture,” Beckta said. The legislation will require all practices to be accredited by either ASTRO, the American College of Radiation Oncology, or the American College of Radiology, essentially capturing their business through a regulation or having practices “face a 2.5% penalty, which is up 1% from the prior version,” Beckta explained. 

The bill also shortens the runway to get accredited from 3 years to 2 years, Beckta noted, stressing the arduousness of the accreditation process as a hurdle for many practices.

But doing the accreditation program does not mean care will get better, Spraker said. In fact, “that is absolutely not the case.”

Another issue: Requirements for medical equipment and quality review periods seem to favor industry over patients and practices, he said, highlighting the potential role of manufacturers in determining if or when equipment updates are required.

“A field like ours has rapidly exploding technology with not-always-clear patient benefit,” said Spraker. “We’re seeing too many examples where people are leveraging that, basically to sell devices instead of to help patients,” he added. 

Furthermore, Beckta noted, the bill allows for reduced reimbursement of between 4% and 7%, depending on the circumstances — a cut to reimbursement that is being justified by saying it’s the only way the bill will get through Congress. But “it’s just a less-bad option than continued cuts to fee-for-service,” Beckta said.

ASTRO leadership has expressed strong support for the bill. In the recent ASTRO press release, Howard M. Sandler, MD, chair of the ASTRO Board of Directors, called the ROCR Act “the only viable policy solution designed to provide payment stability for the field of radiation oncology in 2026 and beyond.” 

The ROCR Act, which is broadly supported by more than 80 organizations, “represents a balanced, evidence-based policy solution to safeguard access to high value cancer treatment for Americans,” Sandler said. 

“I believe in this bill,” Basree added.

Basree touted the replacement of a fee-for-service model with a “value-based payment system, ensuring predictable, fair reimbursement for the field” as a major win for stabilizing Medicare reimbursement. The bill also includes measures to improve patient access, such as providing discounted transportation for patients — a significant need, particularly in rural areas, he explained.

Although not everyone is happy with the bill, ASTRO did aim “to build coalition of support,” Basree said. “It’s an uphill battle, for sure, but we should press forward and hope for the best,” he added.

Even with their concerns, both Spraker and Beckta are optimistic that improvements to the bill can still be made, and urge colleagues to study the bill, speak out, and engage to help promote the best possible policy.

Basree reported receiving reimbursement for meeting travel and lodging as both a Fellow and member of the Association of Residents in Radiation Oncology. Spraker and Beckta reported having no relevant disclosures.

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

A renewed effort to modernize and stabilize Medicare reimbursement for radiation therapy services is underway.

In mid-March, members of Congress reintroduced bipartisan federal legislation that would shift Medicare reimbursement for radiation oncology services from quantity-based payments to episode-based payments and help stabilize the declining rates of reimbursement in the field. 

The Radiation Oncology Case Rate (ROCR) Value Based Payment Program Act, sponsored by two senators and four representatives, would not only “transform” how Medicare reimburses radiation therapy services, it would also “protect access to high quality cancer care and improve outcomes for patients nationwide, while generating savings for Medicare,” according to a recent American Society for Radiation Oncology (ASTRO) press release praising the bill. 

However, the reaction among those in the field has been mixed. Whereas some radiation oncologists are aligned with the bill, others argue that the legislation was crafted without meaningful input from many who will be affected.

“There’s consensus across multiple groups within the house of radiation oncology, hospital groups, and industry, which is incredibly important,” according to Mustafa Basree, DO, a radiation oncology resident who serves on ASTRO’s government relations committee and was part of the discussion on drafting the bill. 

But, Basree acknowledged, “not everybody likes the bill.”

A core complaint is a lack of communication and input from clinicians in the field. “If we’re going to decide to design our own quality program — which is really like a dream from a clinician’s standpoint — we need a meaningful way to come together as a unified field,” said Matthew Spraker, MD, PhD, a radiation oncologist practicing in Denver. In this bill, “we’re not getting any of that.”

 

Impetus for the Bill

Amid dramatic drops in Medicare reimbursement — and with more probably on the horizon — ASTRO announced in January 2024 that the society had partnered with the American College of Radiation Oncology, the American College of Radiology, and the American Society of Clinical Oncology to lobby for payment reform. 

Cuts to Medicare reimbursement were approaching 25% at the time. These declines were related, in part, to changes in how radiation treatment was being delivered. Reimbursement has historically been based on the fraction of radiation given, but the field has increasingly embraced hypofractionated regimens and deescalated approaches, which have led to fewer billable fractions and consequently lower reimbursement. 

A recent study highlighted significant declines in reimbursement based on this shift in care. For instance, greater use of hypofractionation led to declines in reimbursement for technical services in freestanding radiation oncology offices by nearly 17% for breast cancer and 14.2% for prostate cancer between 2016 and 2022. Inflation-adjusted Medicare conversion factors fell 12.2% in hospital outpatient centers and 20.8% in freestanding offices.

These declining reimbursement rates have occurred alongside changes to radiation oncology practice patterns. A recent analysis reported a 51% increase in the number of US practices with at least 10 radiation oncologists between 2015 and 2023, and a 27% decrease in the number of solo practices during the same period. The number of practicing radiation oncologists increased by 16%, but the number of practices employing them decreased by 13%, indicating a trend toward practice consolidation. 

These changes, the analysis found, may affect patients’ access to care. In rural areas, retirement rates were higher and rates of entry of new radiation oncologists was lower compared with urban areas.

The current payment structure “has become untenable,” leading to practice consolidation that threaten patient access, especially in rural and underserved areas, a spokesperson for ASTRO told this news organization last year. 

 

What Is the ROCR Act?

The ROCR ACT was drafted by ASTRO to address these issues and reverse declines in Medicare reimbursement. 

In addition to shifting radiation oncology reimbursement from fraction-based to episode-based, the bill also aims to encourage clinicians to adoptevidence-based shorter treatment regimens, improve safety and quality by supporting new technologies, and generate savings to Medicare by eliminating outdated and costly practices that have not been shown to improve patient outcomes.

When first introduced last year, the bill did not receive a vote in Congress.

A 2025 version of the bill, introduced last month, largely aligns with the 2024 legislation but contains some “enhancements,” such as improving accreditation with increased incentive payments, outlining a revised exemption for practices with limited resources and instituting a transitional payment period for adaptive radiation therapy to allow billing to continue while a new code is created.

 

Mixed Reactions 

How has the radiation oncology community reacted to the latest ROCR Act? 

A recent survey, which included more than 500 practicing radiation oncologists, found that 61% of respondents supported implementing an episode-based payment model such as that proposed in the 2025 legislation, 17.3% neither supported nor opposed it, and 21.6% opposed the model.

“I think this supports this idea that our field would have benefited from much more open discussion in the design phases of the bill,” Spraker told this news organization.

Jason Beckta, MD, PhD, a radiation oncologist at Rutland Regional Medical Center, Vermont, agreed. 

While on board with the concept of reform and episode-based payment, given what Beckta called “the absolute absurdity of the cuts in radiation oncology,” he took issue with the lack of transparency in the rollout of the bill.

The announcement about the 2025 version of the ROCR Act came as “a complete surprise — out of nowhere — except to insiders,” Beckta said.

ASTRO held a town hall in February 2025 “featuring new information and discussion” regarding ROCR 2025, but the bill had already been finalized for submission at that point, Beckta said. 

And although Beckta and Spraker believe ASTRO had good intentions, the physicians highlighted concerns with several aspects of the bill.

“What upsets me most is the blatant regulatory capture,” Beckta said. The legislation will require all practices to be accredited by either ASTRO, the American College of Radiation Oncology, or the American College of Radiology, essentially capturing their business through a regulation or having practices “face a 2.5% penalty, which is up 1% from the prior version,” Beckta explained. 

The bill also shortens the runway to get accredited from 3 years to 2 years, Beckta noted, stressing the arduousness of the accreditation process as a hurdle for many practices.

But doing the accreditation program does not mean care will get better, Spraker said. In fact, “that is absolutely not the case.”

Another issue: Requirements for medical equipment and quality review periods seem to favor industry over patients and practices, he said, highlighting the potential role of manufacturers in determining if or when equipment updates are required.

“A field like ours has rapidly exploding technology with not-always-clear patient benefit,” said Spraker. “We’re seeing too many examples where people are leveraging that, basically to sell devices instead of to help patients,” he added. 

Furthermore, Beckta noted, the bill allows for reduced reimbursement of between 4% and 7%, depending on the circumstances — a cut to reimbursement that is being justified by saying it’s the only way the bill will get through Congress. But “it’s just a less-bad option than continued cuts to fee-for-service,” Beckta said.

ASTRO leadership has expressed strong support for the bill. In the recent ASTRO press release, Howard M. Sandler, MD, chair of the ASTRO Board of Directors, called the ROCR Act “the only viable policy solution designed to provide payment stability for the field of radiation oncology in 2026 and beyond.” 

The ROCR Act, which is broadly supported by more than 80 organizations, “represents a balanced, evidence-based policy solution to safeguard access to high value cancer treatment for Americans,” Sandler said. 

“I believe in this bill,” Basree added.

Basree touted the replacement of a fee-for-service model with a “value-based payment system, ensuring predictable, fair reimbursement for the field” as a major win for stabilizing Medicare reimbursement. The bill also includes measures to improve patient access, such as providing discounted transportation for patients — a significant need, particularly in rural areas, he explained.

Although not everyone is happy with the bill, ASTRO did aim “to build coalition of support,” Basree said. “It’s an uphill battle, for sure, but we should press forward and hope for the best,” he added.

Even with their concerns, both Spraker and Beckta are optimistic that improvements to the bill can still be made, and urge colleagues to study the bill, speak out, and engage to help promote the best possible policy.

Basree reported receiving reimbursement for meeting travel and lodging as both a Fellow and member of the Association of Residents in Radiation Oncology. Spraker and Beckta reported having no relevant disclosures.

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

A renewed effort to modernize and stabilize Medicare reimbursement for radiation therapy services is underway.

In mid-March, members of Congress reintroduced bipartisan federal legislation that would shift Medicare reimbursement for radiation oncology services from quantity-based payments to episode-based payments and help stabilize the declining rates of reimbursement in the field. 

The Radiation Oncology Case Rate (ROCR) Value Based Payment Program Act, sponsored by two senators and four representatives, would not only “transform” how Medicare reimburses radiation therapy services, it would also “protect access to high quality cancer care and improve outcomes for patients nationwide, while generating savings for Medicare,” according to a recent American Society for Radiation Oncology (ASTRO) press release praising the bill. 

However, the reaction among those in the field has been mixed. Whereas some radiation oncologists are aligned with the bill, others argue that the legislation was crafted without meaningful input from many who will be affected.

“There’s consensus across multiple groups within the house of radiation oncology, hospital groups, and industry, which is incredibly important,” according to Mustafa Basree, DO, a radiation oncology resident who serves on ASTRO’s government relations committee and was part of the discussion on drafting the bill. 

But, Basree acknowledged, “not everybody likes the bill.”

A core complaint is a lack of communication and input from clinicians in the field. “If we’re going to decide to design our own quality program — which is really like a dream from a clinician’s standpoint — we need a meaningful way to come together as a unified field,” said Matthew Spraker, MD, PhD, a radiation oncologist practicing in Denver. In this bill, “we’re not getting any of that.”

 

Impetus for the Bill

Amid dramatic drops in Medicare reimbursement — and with more probably on the horizon — ASTRO announced in January 2024 that the society had partnered with the American College of Radiation Oncology, the American College of Radiology, and the American Society of Clinical Oncology to lobby for payment reform. 

Cuts to Medicare reimbursement were approaching 25% at the time. These declines were related, in part, to changes in how radiation treatment was being delivered. Reimbursement has historically been based on the fraction of radiation given, but the field has increasingly embraced hypofractionated regimens and deescalated approaches, which have led to fewer billable fractions and consequently lower reimbursement. 

A recent study highlighted significant declines in reimbursement based on this shift in care. For instance, greater use of hypofractionation led to declines in reimbursement for technical services in freestanding radiation oncology offices by nearly 17% for breast cancer and 14.2% for prostate cancer between 2016 and 2022. Inflation-adjusted Medicare conversion factors fell 12.2% in hospital outpatient centers and 20.8% in freestanding offices.

These declining reimbursement rates have occurred alongside changes to radiation oncology practice patterns. A recent analysis reported a 51% increase in the number of US practices with at least 10 radiation oncologists between 2015 and 2023, and a 27% decrease in the number of solo practices during the same period. The number of practicing radiation oncologists increased by 16%, but the number of practices employing them decreased by 13%, indicating a trend toward practice consolidation. 

These changes, the analysis found, may affect patients’ access to care. In rural areas, retirement rates were higher and rates of entry of new radiation oncologists was lower compared with urban areas.

The current payment structure “has become untenable,” leading to practice consolidation that threaten patient access, especially in rural and underserved areas, a spokesperson for ASTRO told this news organization last year. 

 

What Is the ROCR Act?

The ROCR ACT was drafted by ASTRO to address these issues and reverse declines in Medicare reimbursement. 

In addition to shifting radiation oncology reimbursement from fraction-based to episode-based, the bill also aims to encourage clinicians to adoptevidence-based shorter treatment regimens, improve safety and quality by supporting new technologies, and generate savings to Medicare by eliminating outdated and costly practices that have not been shown to improve patient outcomes.

When first introduced last year, the bill did not receive a vote in Congress.

A 2025 version of the bill, introduced last month, largely aligns with the 2024 legislation but contains some “enhancements,” such as improving accreditation with increased incentive payments, outlining a revised exemption for practices with limited resources and instituting a transitional payment period for adaptive radiation therapy to allow billing to continue while a new code is created.

 

Mixed Reactions 

How has the radiation oncology community reacted to the latest ROCR Act? 

A recent survey, which included more than 500 practicing radiation oncologists, found that 61% of respondents supported implementing an episode-based payment model such as that proposed in the 2025 legislation, 17.3% neither supported nor opposed it, and 21.6% opposed the model.

“I think this supports this idea that our field would have benefited from much more open discussion in the design phases of the bill,” Spraker told this news organization.

Jason Beckta, MD, PhD, a radiation oncologist at Rutland Regional Medical Center, Vermont, agreed. 

While on board with the concept of reform and episode-based payment, given what Beckta called “the absolute absurdity of the cuts in radiation oncology,” he took issue with the lack of transparency in the rollout of the bill.

The announcement about the 2025 version of the ROCR Act came as “a complete surprise — out of nowhere — except to insiders,” Beckta said.

ASTRO held a town hall in February 2025 “featuring new information and discussion” regarding ROCR 2025, but the bill had already been finalized for submission at that point, Beckta said. 

And although Beckta and Spraker believe ASTRO had good intentions, the physicians highlighted concerns with several aspects of the bill.

“What upsets me most is the blatant regulatory capture,” Beckta said. The legislation will require all practices to be accredited by either ASTRO, the American College of Radiation Oncology, or the American College of Radiology, essentially capturing their business through a regulation or having practices “face a 2.5% penalty, which is up 1% from the prior version,” Beckta explained. 

The bill also shortens the runway to get accredited from 3 years to 2 years, Beckta noted, stressing the arduousness of the accreditation process as a hurdle for many practices.

But doing the accreditation program does not mean care will get better, Spraker said. In fact, “that is absolutely not the case.”

Another issue: Requirements for medical equipment and quality review periods seem to favor industry over patients and practices, he said, highlighting the potential role of manufacturers in determining if or when equipment updates are required.

“A field like ours has rapidly exploding technology with not-always-clear patient benefit,” said Spraker. “We’re seeing too many examples where people are leveraging that, basically to sell devices instead of to help patients,” he added. 

Furthermore, Beckta noted, the bill allows for reduced reimbursement of between 4% and 7%, depending on the circumstances — a cut to reimbursement that is being justified by saying it’s the only way the bill will get through Congress. But “it’s just a less-bad option than continued cuts to fee-for-service,” Beckta said.

ASTRO leadership has expressed strong support for the bill. In the recent ASTRO press release, Howard M. Sandler, MD, chair of the ASTRO Board of Directors, called the ROCR Act “the only viable policy solution designed to provide payment stability for the field of radiation oncology in 2026 and beyond.” 

The ROCR Act, which is broadly supported by more than 80 organizations, “represents a balanced, evidence-based policy solution to safeguard access to high value cancer treatment for Americans,” Sandler said. 

“I believe in this bill,” Basree added.

Basree touted the replacement of a fee-for-service model with a “value-based payment system, ensuring predictable, fair reimbursement for the field” as a major win for stabilizing Medicare reimbursement. The bill also includes measures to improve patient access, such as providing discounted transportation for patients — a significant need, particularly in rural areas, he explained.

Although not everyone is happy with the bill, ASTRO did aim “to build coalition of support,” Basree said. “It’s an uphill battle, for sure, but we should press forward and hope for the best,” he added.

Even with their concerns, both Spraker and Beckta are optimistic that improvements to the bill can still be made, and urge colleagues to study the bill, speak out, and engage to help promote the best possible policy.

Basree reported receiving reimbursement for meeting travel and lodging as both a Fellow and member of the Association of Residents in Radiation Oncology. Spraker and Beckta reported having no relevant disclosures.

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

Patient navigation was more effective than usual care in increasing follow-up colonoscopy rates after an abnormal stool test result, a new randomized controlled trial revealed.

The intervention led to a significant 13-point increase in follow-up colonoscopy completion at 1 year, compared with usual care (55.1% vs 42.1%), according the study, which was published online in Annals of Internal Medicine.

 

“Patients with an abnormal fecal test results have about a 1 in 20 chance of having colorectal cancer found, and many more will be found to have advanced adenomas that can be removed to prevent cancer,” Gloria Coronado, PhD, of Kaiser Permanente Center for Health Research, Portland, Oregon, and University of Arizona Cancer Center, Tucson, said in an interview.

“It is critical that these patients get a follow-up colonoscopy,” she said. “Patient navigation can accomplish this goal.”

 

‘Highly Effective’ Intervention

Researchers compared the effectiveness of a patient navigation program with that of usual care outreach in increasing follow-up colonoscopy completion after an abnormal stool test. They also developed a risk-prediction model that calculated a patient’s probability of obtaining a follow-up colonoscopy without navigation to determine if the addition of this intervention had a greater impact on those determined to be less likely to follow through.

The study included 967 patients from a community health center in Washington State who received an abnormal fecal test result within the prior month. The mean age of participants was 61 years, approximately 45% were women and 77% were White, and 18% preferred a Spanish-language intervention. In total, 479 patients received the intervention and 488 received usual care.

The intervention was delivered by a patient navigator who mailed introductory letters, sent text messages, and made live phone calls. In the calls, the navigators addressed the topics of barrier assessment and resolution, bowel preparation instruction and reminders, colonoscopy check-in, and understanding colonoscopy results and retesting intervals.

Patients in the usual-care group were contacted by a referral coordinator to schedule a follow-up colonoscopy appointment. If they couldn’t be reached initially, up to two follow-up attempts were made at 30 and 45 days after the referral date.

Patient navigation resulted in a significant 13% increase in follow-up, and those in this group completed a colonoscopy 27 days sooner than those in the usual care group (mean, 229 days vs 256 days).

Contrary to the authors’ expectation, the effectiveness of the intervention did not vary by patients’ predicted likelihood of obtaining a colonoscopy without navigation.

Notably, 20.3% of patients were unreachable or lost to follow-up, and 29.7% did not receive navigation. Among the 479 patients assigned to navigation, 79 (16.5%) declined participation and 56 (11.7%) were never reached.

The study was primarily conducted during the height of the COVID-19 pandemic, which created additional systemic and individual barriers to completing colonoscopies.

Nevertheless, the authors wrote, “our findings suggest that patient navigation is highly effective for patients eligible for colonoscopy.”

“Most patients who were reached were contacted with six or fewer phone attempts,” Coronado noted. “Further efforts are needed to determine how to reach and motivate patients [who did not participate] to get a follow-up colonoscopy.”

Coronado and colleagues are exploring ways to leverage artificial intelligence and virtual approaches to augment patient navigation programs — for example, by using a virtual navigator or low-cost automated tools to provide education to build patient confidence in getting a colonoscopy.

 

‘A Promising Tool’

“Colonoscopy completion after positive stool-based testing is critical to mitigating the impact of colon cancer,” commented Rajiv Bhuta, MD, assistant professor of clinical gastroenterology & hepatology, Lewis Katz School of Medicine, Temple University, Philadelphia, who was not involved in the study. “While prior studies assessing navigation have demonstrated improvements, none were as large enrollment-wise or as generalizable as the current study.”

That said, Bhuta said in an interview that the study could have provided more detail about coordination and communication with local gastrointestinal practices.

“Local ordering and prescribing practices vary and can significantly impact compliance rates. Were colonoscopies completed via an open access pathway or were the patients required to see a gastroenterologist first? How long was the average wait time for colonoscopy once scheduled? What were the local policies on requiring an escort after the procedure?”

He also noted that some aspects of the study — such as access to reduced-cost specialty care and free ride-share services — may limit generalizable to settings without such resources.

He added: “Although patient navigators for cancer treatment have mandated reimbursement, there is no current reimbursement for navigators for abnormal screening tests, another barrier to wide-spread implementation.”

Bhuta said that the dropout rate in the study mirrors that of his own real-world practice, which serves a high-risk, low-resource community. “I would specifically like to see research that provides behavioral insights on why patients respond positively to navigation — whether it is due to reminders, emotional support, or logistical assistance. Is it systemic barriers or patient disinterest or both that drives noncompliance?”

Despite these uncertainties and the need to refine implementation logistics, Bhuta concluded, “this strategy is a promising tool to reduce disparities and improve colorectal cancer outcomes. Clinicians should advocate for or implement structured follow-up systems, particularly in high-risk populations.”

The study was funded by the US National Cancer Institute. Coronado received a grant/contract from Guardant Health. Bhuta declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Patient navigation was more effective than usual care in increasing follow-up colonoscopy rates after an abnormal stool test result, a new randomized controlled trial revealed.

The intervention led to a significant 13-point increase in follow-up colonoscopy completion at 1 year, compared with usual care (55.1% vs 42.1%), according the study, which was published online in Annals of Internal Medicine.

 

“Patients with an abnormal fecal test results have about a 1 in 20 chance of having colorectal cancer found, and many more will be found to have advanced adenomas that can be removed to prevent cancer,” Gloria Coronado, PhD, of Kaiser Permanente Center for Health Research, Portland, Oregon, and University of Arizona Cancer Center, Tucson, said in an interview.

“It is critical that these patients get a follow-up colonoscopy,” she said. “Patient navigation can accomplish this goal.”

 

‘Highly Effective’ Intervention

Researchers compared the effectiveness of a patient navigation program with that of usual care outreach in increasing follow-up colonoscopy completion after an abnormal stool test. They also developed a risk-prediction model that calculated a patient’s probability of obtaining a follow-up colonoscopy without navigation to determine if the addition of this intervention had a greater impact on those determined to be less likely to follow through.

The study included 967 patients from a community health center in Washington State who received an abnormal fecal test result within the prior month. The mean age of participants was 61 years, approximately 45% were women and 77% were White, and 18% preferred a Spanish-language intervention. In total, 479 patients received the intervention and 488 received usual care.

The intervention was delivered by a patient navigator who mailed introductory letters, sent text messages, and made live phone calls. In the calls, the navigators addressed the topics of barrier assessment and resolution, bowel preparation instruction and reminders, colonoscopy check-in, and understanding colonoscopy results and retesting intervals.

Patients in the usual-care group were contacted by a referral coordinator to schedule a follow-up colonoscopy appointment. If they couldn’t be reached initially, up to two follow-up attempts were made at 30 and 45 days after the referral date.

Patient navigation resulted in a significant 13% increase in follow-up, and those in this group completed a colonoscopy 27 days sooner than those in the usual care group (mean, 229 days vs 256 days).

Contrary to the authors’ expectation, the effectiveness of the intervention did not vary by patients’ predicted likelihood of obtaining a colonoscopy without navigation.

Notably, 20.3% of patients were unreachable or lost to follow-up, and 29.7% did not receive navigation. Among the 479 patients assigned to navigation, 79 (16.5%) declined participation and 56 (11.7%) were never reached.

The study was primarily conducted during the height of the COVID-19 pandemic, which created additional systemic and individual barriers to completing colonoscopies.

Nevertheless, the authors wrote, “our findings suggest that patient navigation is highly effective for patients eligible for colonoscopy.”

“Most patients who were reached were contacted with six or fewer phone attempts,” Coronado noted. “Further efforts are needed to determine how to reach and motivate patients [who did not participate] to get a follow-up colonoscopy.”

Coronado and colleagues are exploring ways to leverage artificial intelligence and virtual approaches to augment patient navigation programs — for example, by using a virtual navigator or low-cost automated tools to provide education to build patient confidence in getting a colonoscopy.

 

‘A Promising Tool’

“Colonoscopy completion after positive stool-based testing is critical to mitigating the impact of colon cancer,” commented Rajiv Bhuta, MD, assistant professor of clinical gastroenterology & hepatology, Lewis Katz School of Medicine, Temple University, Philadelphia, who was not involved in the study. “While prior studies assessing navigation have demonstrated improvements, none were as large enrollment-wise or as generalizable as the current study.”

That said, Bhuta said in an interview that the study could have provided more detail about coordination and communication with local gastrointestinal practices.

“Local ordering and prescribing practices vary and can significantly impact compliance rates. Were colonoscopies completed via an open access pathway or were the patients required to see a gastroenterologist first? How long was the average wait time for colonoscopy once scheduled? What were the local policies on requiring an escort after the procedure?”

He also noted that some aspects of the study — such as access to reduced-cost specialty care and free ride-share services — may limit generalizable to settings without such resources.

He added: “Although patient navigators for cancer treatment have mandated reimbursement, there is no current reimbursement for navigators for abnormal screening tests, another barrier to wide-spread implementation.”

Bhuta said that the dropout rate in the study mirrors that of his own real-world practice, which serves a high-risk, low-resource community. “I would specifically like to see research that provides behavioral insights on why patients respond positively to navigation — whether it is due to reminders, emotional support, or logistical assistance. Is it systemic barriers or patient disinterest or both that drives noncompliance?”

Despite these uncertainties and the need to refine implementation logistics, Bhuta concluded, “this strategy is a promising tool to reduce disparities and improve colorectal cancer outcomes. Clinicians should advocate for or implement structured follow-up systems, particularly in high-risk populations.”

The study was funded by the US National Cancer Institute. Coronado received a grant/contract from Guardant Health. Bhuta declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Patient navigation was more effective than usual care in increasing follow-up colonoscopy rates after an abnormal stool test result, a new randomized controlled trial revealed.

The intervention led to a significant 13-point increase in follow-up colonoscopy completion at 1 year, compared with usual care (55.1% vs 42.1%), according the study, which was published online in Annals of Internal Medicine.

 

“Patients with an abnormal fecal test results have about a 1 in 20 chance of having colorectal cancer found, and many more will be found to have advanced adenomas that can be removed to prevent cancer,” Gloria Coronado, PhD, of Kaiser Permanente Center for Health Research, Portland, Oregon, and University of Arizona Cancer Center, Tucson, said in an interview.

“It is critical that these patients get a follow-up colonoscopy,” she said. “Patient navigation can accomplish this goal.”

 

‘Highly Effective’ Intervention

Researchers compared the effectiveness of a patient navigation program with that of usual care outreach in increasing follow-up colonoscopy completion after an abnormal stool test. They also developed a risk-prediction model that calculated a patient’s probability of obtaining a follow-up colonoscopy without navigation to determine if the addition of this intervention had a greater impact on those determined to be less likely to follow through.

The study included 967 patients from a community health center in Washington State who received an abnormal fecal test result within the prior month. The mean age of participants was 61 years, approximately 45% were women and 77% were White, and 18% preferred a Spanish-language intervention. In total, 479 patients received the intervention and 488 received usual care.

The intervention was delivered by a patient navigator who mailed introductory letters, sent text messages, and made live phone calls. In the calls, the navigators addressed the topics of barrier assessment and resolution, bowel preparation instruction and reminders, colonoscopy check-in, and understanding colonoscopy results and retesting intervals.

Patients in the usual-care group were contacted by a referral coordinator to schedule a follow-up colonoscopy appointment. If they couldn’t be reached initially, up to two follow-up attempts were made at 30 and 45 days after the referral date.

Patient navigation resulted in a significant 13% increase in follow-up, and those in this group completed a colonoscopy 27 days sooner than those in the usual care group (mean, 229 days vs 256 days).

Contrary to the authors’ expectation, the effectiveness of the intervention did not vary by patients’ predicted likelihood of obtaining a colonoscopy without navigation.

Notably, 20.3% of patients were unreachable or lost to follow-up, and 29.7% did not receive navigation. Among the 479 patients assigned to navigation, 79 (16.5%) declined participation and 56 (11.7%) were never reached.

The study was primarily conducted during the height of the COVID-19 pandemic, which created additional systemic and individual barriers to completing colonoscopies.

Nevertheless, the authors wrote, “our findings suggest that patient navigation is highly effective for patients eligible for colonoscopy.”

“Most patients who were reached were contacted with six or fewer phone attempts,” Coronado noted. “Further efforts are needed to determine how to reach and motivate patients [who did not participate] to get a follow-up colonoscopy.”

Coronado and colleagues are exploring ways to leverage artificial intelligence and virtual approaches to augment patient navigation programs — for example, by using a virtual navigator or low-cost automated tools to provide education to build patient confidence in getting a colonoscopy.

 

‘A Promising Tool’

“Colonoscopy completion after positive stool-based testing is critical to mitigating the impact of colon cancer,” commented Rajiv Bhuta, MD, assistant professor of clinical gastroenterology & hepatology, Lewis Katz School of Medicine, Temple University, Philadelphia, who was not involved in the study. “While prior studies assessing navigation have demonstrated improvements, none were as large enrollment-wise or as generalizable as the current study.”

That said, Bhuta said in an interview that the study could have provided more detail about coordination and communication with local gastrointestinal practices.

“Local ordering and prescribing practices vary and can significantly impact compliance rates. Were colonoscopies completed via an open access pathway or were the patients required to see a gastroenterologist first? How long was the average wait time for colonoscopy once scheduled? What were the local policies on requiring an escort after the procedure?”

He also noted that some aspects of the study — such as access to reduced-cost specialty care and free ride-share services — may limit generalizable to settings without such resources.

He added: “Although patient navigators for cancer treatment have mandated reimbursement, there is no current reimbursement for navigators for abnormal screening tests, another barrier to wide-spread implementation.”

Bhuta said that the dropout rate in the study mirrors that of his own real-world practice, which serves a high-risk, low-resource community. “I would specifically like to see research that provides behavioral insights on why patients respond positively to navigation — whether it is due to reminders, emotional support, or logistical assistance. Is it systemic barriers or patient disinterest or both that drives noncompliance?”

Despite these uncertainties and the need to refine implementation logistics, Bhuta concluded, “this strategy is a promising tool to reduce disparities and improve colorectal cancer outcomes. Clinicians should advocate for or implement structured follow-up systems, particularly in high-risk populations.”

The study was funded by the US National Cancer Institute. Coronado received a grant/contract from Guardant Health. Bhuta declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.