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Physician-Scientist Taps into Microbiome to Fight Cancer
The lowest point in the nascent career of Neelendu Dey, MD, helped seal his fate as a physician-scientist.
He had just started his first year as a resident at University of California, San Francisco. One of his patients was a 30-year-old woman who was dying of metastatic colorectal cancer. “I was in my mid-20s interacting with an individual just a few years older than I am, going through one of the most terrible health outcomes one could imagine,” Dr. Dey said.
He remembers asking the patient what he could do for her, how he could make her feel more comfortable. “That feeling of helplessness, particularly as we think about young people developing cancer, it really stuck with me through the years,” he said.
In an interview, he talked about his dual role as a physician and scientist, and how those two interests are guiding his research in precancerous conditions of the colon.
Cases like that of the young woman with colon cancer “really help drive the urgency of the work we do, and the research questions we ask, as we try to move the ball forward and help folks at earlier stages,” he said.
Q: Why did you choose GI?
When you think about what sorts of chronic diseases really impact your quality of life, gut health is one of the chief contributors among various aspects of health. And that really appealed to me — the ability to take someone who is essentially handicapped by a series of illnesses and symptoms that derive from the GI tract and enable them to return to the person they want to be, to be productive in the way that they want to be, and have a rewarding life.
As I thought about how I wanted to contribute to the future of medicine, one of the ways in which I’ve always thought that I would do that is through research. When I considered the fields that really appealed to me, both from that clinical standpoint and research standpoint, GI was one that really stood out. There has been a lot of exciting research going on in GI. My lab currently studies the microbiome, and I feel like this is an area in which we can contribute.
Q: What role does digestive health play in overall health?
Obviously, the direct answer is gut health is so critical in something like nutritional intake. Some GI symptoms, if your gut health has gone awry, can really be detrimental in terms of quality of life. But one less obvious role that digestive health plays is its long-term effects. We’re starting to appreciate that gut health, the gut microbiome, and gut immune education are probably long-term players. Some experiences in early life might shape our immunity in ways that have consequences for us much later in life. Whether we get early life antibiotics, for example, may potentially contribute to colorectal cancer down the line. Thinking about the long-term players is more challenging, but it’s also an appealing opportunity as we think about how we can shape medicine moving forward.
Q: What practice challenges have you faced in your career?
First, being a physician-scientist. It’s challenging to be either a physician alone or to be a researcher alone. And trying to do both includes the challenges of both individual worlds. It just takes more time to get all the prerequisite training. And second, there are just challenges with getting the opportunities to contribute in the ways that you want — to get the research funding, to get the papers out, things like that.
Q: Tell me about the work you’ve been doing in your lab to develop microbiome-based strategies for preventing and treating cancer.
The microbiome presents several opportunities when it comes to cancer prevention. One is identifying markers of cancer risk, or of general good health down the line. Some of those biomarkers could — potentially — feed directly into personalized risk assessment and maybe even inform a future screening strategy. The second opportunity the microbiome presents is if we identify a microbe that influences your cancer risk, can we then understand and exploit, or utilize, that mechanism to mitigate cancer risk in the future? Our lab has done work looking at subspecies levels of microbes that track with health or cancer. We’ve done some work to identify what these subspecies groupings are and have identified some links to certain precancerous changes in the colon. We think that there’s an opportunity here for future interventions.
Q: Have you published other papers?
We recently published another paper describing how some microbes can interact with a tumor suppressor gene and are influenced in a sex-biased manner to drive tumorigenesis in a mouse model. We think, based on what we’re seeing in human data, that there may be some relationships and we’re exploring that now as well.
Q: What is your vision for the future in GI, and in your career?
The vision that I have is to create clinical tools that can expand our reach and our effectiveness and cancer prevention. I think that there are opportunities for leveraging microbiome research to accomplish this. And one outcome I could imagine is leveraging some of these insights to expand noninvasive screening at even earlier ages than we do now. I mean, we just dialed back the recommended age for colonoscopy for average risk individuals to 45. But I could envision a future in which noninvasive screening starts earlier, in which the first stool-based tests that we deploy to assess personalized risk are used in the pediatric clinic.
Lightning Round
Texting or talking?
Talking
Favorite city in the United States besides the one you live in?
St. Louis
Cat or dog person?
Both
If you weren’t a GI, what would you be?
Musician
Best place you went on vacation?
Borneo
Favorite sport?
Soccer
Favorite ice cream?
Cashew-based salted caramel
What song do you have to sing along with when you hear it?
Sweet Child of Mine
Favorite movie or TV show?
25th Hour or Shawshank Redemption
Optimist or Pessimist?
Optimist
The lowest point in the nascent career of Neelendu Dey, MD, helped seal his fate as a physician-scientist.
He had just started his first year as a resident at University of California, San Francisco. One of his patients was a 30-year-old woman who was dying of metastatic colorectal cancer. “I was in my mid-20s interacting with an individual just a few years older than I am, going through one of the most terrible health outcomes one could imagine,” Dr. Dey said.
He remembers asking the patient what he could do for her, how he could make her feel more comfortable. “That feeling of helplessness, particularly as we think about young people developing cancer, it really stuck with me through the years,” he said.
In an interview, he talked about his dual role as a physician and scientist, and how those two interests are guiding his research in precancerous conditions of the colon.
Cases like that of the young woman with colon cancer “really help drive the urgency of the work we do, and the research questions we ask, as we try to move the ball forward and help folks at earlier stages,” he said.
Q: Why did you choose GI?
When you think about what sorts of chronic diseases really impact your quality of life, gut health is one of the chief contributors among various aspects of health. And that really appealed to me — the ability to take someone who is essentially handicapped by a series of illnesses and symptoms that derive from the GI tract and enable them to return to the person they want to be, to be productive in the way that they want to be, and have a rewarding life.
As I thought about how I wanted to contribute to the future of medicine, one of the ways in which I’ve always thought that I would do that is through research. When I considered the fields that really appealed to me, both from that clinical standpoint and research standpoint, GI was one that really stood out. There has been a lot of exciting research going on in GI. My lab currently studies the microbiome, and I feel like this is an area in which we can contribute.
Q: What role does digestive health play in overall health?
Obviously, the direct answer is gut health is so critical in something like nutritional intake. Some GI symptoms, if your gut health has gone awry, can really be detrimental in terms of quality of life. But one less obvious role that digestive health plays is its long-term effects. We’re starting to appreciate that gut health, the gut microbiome, and gut immune education are probably long-term players. Some experiences in early life might shape our immunity in ways that have consequences for us much later in life. Whether we get early life antibiotics, for example, may potentially contribute to colorectal cancer down the line. Thinking about the long-term players is more challenging, but it’s also an appealing opportunity as we think about how we can shape medicine moving forward.
Q: What practice challenges have you faced in your career?
First, being a physician-scientist. It’s challenging to be either a physician alone or to be a researcher alone. And trying to do both includes the challenges of both individual worlds. It just takes more time to get all the prerequisite training. And second, there are just challenges with getting the opportunities to contribute in the ways that you want — to get the research funding, to get the papers out, things like that.
Q: Tell me about the work you’ve been doing in your lab to develop microbiome-based strategies for preventing and treating cancer.
The microbiome presents several opportunities when it comes to cancer prevention. One is identifying markers of cancer risk, or of general good health down the line. Some of those biomarkers could — potentially — feed directly into personalized risk assessment and maybe even inform a future screening strategy. The second opportunity the microbiome presents is if we identify a microbe that influences your cancer risk, can we then understand and exploit, or utilize, that mechanism to mitigate cancer risk in the future? Our lab has done work looking at subspecies levels of microbes that track with health or cancer. We’ve done some work to identify what these subspecies groupings are and have identified some links to certain precancerous changes in the colon. We think that there’s an opportunity here for future interventions.
Q: Have you published other papers?
We recently published another paper describing how some microbes can interact with a tumor suppressor gene and are influenced in a sex-biased manner to drive tumorigenesis in a mouse model. We think, based on what we’re seeing in human data, that there may be some relationships and we’re exploring that now as well.
Q: What is your vision for the future in GI, and in your career?
The vision that I have is to create clinical tools that can expand our reach and our effectiveness and cancer prevention. I think that there are opportunities for leveraging microbiome research to accomplish this. And one outcome I could imagine is leveraging some of these insights to expand noninvasive screening at even earlier ages than we do now. I mean, we just dialed back the recommended age for colonoscopy for average risk individuals to 45. But I could envision a future in which noninvasive screening starts earlier, in which the first stool-based tests that we deploy to assess personalized risk are used in the pediatric clinic.
Lightning Round
Texting or talking?
Talking
Favorite city in the United States besides the one you live in?
St. Louis
Cat or dog person?
Both
If you weren’t a GI, what would you be?
Musician
Best place you went on vacation?
Borneo
Favorite sport?
Soccer
Favorite ice cream?
Cashew-based salted caramel
What song do you have to sing along with when you hear it?
Sweet Child of Mine
Favorite movie or TV show?
25th Hour or Shawshank Redemption
Optimist or Pessimist?
Optimist
The lowest point in the nascent career of Neelendu Dey, MD, helped seal his fate as a physician-scientist.
He had just started his first year as a resident at University of California, San Francisco. One of his patients was a 30-year-old woman who was dying of metastatic colorectal cancer. “I was in my mid-20s interacting with an individual just a few years older than I am, going through one of the most terrible health outcomes one could imagine,” Dr. Dey said.
He remembers asking the patient what he could do for her, how he could make her feel more comfortable. “That feeling of helplessness, particularly as we think about young people developing cancer, it really stuck with me through the years,” he said.
In an interview, he talked about his dual role as a physician and scientist, and how those two interests are guiding his research in precancerous conditions of the colon.
Cases like that of the young woman with colon cancer “really help drive the urgency of the work we do, and the research questions we ask, as we try to move the ball forward and help folks at earlier stages,” he said.
Q: Why did you choose GI?
When you think about what sorts of chronic diseases really impact your quality of life, gut health is one of the chief contributors among various aspects of health. And that really appealed to me — the ability to take someone who is essentially handicapped by a series of illnesses and symptoms that derive from the GI tract and enable them to return to the person they want to be, to be productive in the way that they want to be, and have a rewarding life.
As I thought about how I wanted to contribute to the future of medicine, one of the ways in which I’ve always thought that I would do that is through research. When I considered the fields that really appealed to me, both from that clinical standpoint and research standpoint, GI was one that really stood out. There has been a lot of exciting research going on in GI. My lab currently studies the microbiome, and I feel like this is an area in which we can contribute.
Q: What role does digestive health play in overall health?
Obviously, the direct answer is gut health is so critical in something like nutritional intake. Some GI symptoms, if your gut health has gone awry, can really be detrimental in terms of quality of life. But one less obvious role that digestive health plays is its long-term effects. We’re starting to appreciate that gut health, the gut microbiome, and gut immune education are probably long-term players. Some experiences in early life might shape our immunity in ways that have consequences for us much later in life. Whether we get early life antibiotics, for example, may potentially contribute to colorectal cancer down the line. Thinking about the long-term players is more challenging, but it’s also an appealing opportunity as we think about how we can shape medicine moving forward.
Q: What practice challenges have you faced in your career?
First, being a physician-scientist. It’s challenging to be either a physician alone or to be a researcher alone. And trying to do both includes the challenges of both individual worlds. It just takes more time to get all the prerequisite training. And second, there are just challenges with getting the opportunities to contribute in the ways that you want — to get the research funding, to get the papers out, things like that.
Q: Tell me about the work you’ve been doing in your lab to develop microbiome-based strategies for preventing and treating cancer.
The microbiome presents several opportunities when it comes to cancer prevention. One is identifying markers of cancer risk, or of general good health down the line. Some of those biomarkers could — potentially — feed directly into personalized risk assessment and maybe even inform a future screening strategy. The second opportunity the microbiome presents is if we identify a microbe that influences your cancer risk, can we then understand and exploit, or utilize, that mechanism to mitigate cancer risk in the future? Our lab has done work looking at subspecies levels of microbes that track with health or cancer. We’ve done some work to identify what these subspecies groupings are and have identified some links to certain precancerous changes in the colon. We think that there’s an opportunity here for future interventions.
Q: Have you published other papers?
We recently published another paper describing how some microbes can interact with a tumor suppressor gene and are influenced in a sex-biased manner to drive tumorigenesis in a mouse model. We think, based on what we’re seeing in human data, that there may be some relationships and we’re exploring that now as well.
Q: What is your vision for the future in GI, and in your career?
The vision that I have is to create clinical tools that can expand our reach and our effectiveness and cancer prevention. I think that there are opportunities for leveraging microbiome research to accomplish this. And one outcome I could imagine is leveraging some of these insights to expand noninvasive screening at even earlier ages than we do now. I mean, we just dialed back the recommended age for colonoscopy for average risk individuals to 45. But I could envision a future in which noninvasive screening starts earlier, in which the first stool-based tests that we deploy to assess personalized risk are used in the pediatric clinic.
Lightning Round
Texting or talking?
Talking
Favorite city in the United States besides the one you live in?
St. Louis
Cat or dog person?
Both
If you weren’t a GI, what would you be?
Musician
Best place you went on vacation?
Borneo
Favorite sport?
Soccer
Favorite ice cream?
Cashew-based salted caramel
What song do you have to sing along with when you hear it?
Sweet Child of Mine
Favorite movie or TV show?
25th Hour or Shawshank Redemption
Optimist or Pessimist?
Optimist
Breakthrough Blood Test for Colorectal Cancer Gets Green Light
The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.
Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.
The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.
While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.
In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.
If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.
“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
A version of this article appeared on WebMD.com.
The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.
Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.
The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.
While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.
In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.
If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.
“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
A version of this article appeared on WebMD.com.
The FDA on July 29 approved the test, called Shield, which can accurately detect tumors in the colon or rectum about 87% of the time when the cancer is in treatable early stages. The approval was announced July 29 by the test’s maker, Guardant Health, and comes just months after promising clinical trial results were published in The New England Journal of Medicine.
Colorectal cancer is among the most common types of cancer diagnosed in the United States each year, along with being one of the leading causes of cancer deaths. The condition is treatable in early stages, but about 1 in 3 people don’t stay up to date on regular screenings, which should begin at age 45.
The simplicity of a blood test could make it more likely for people to be screened for and, ultimately, survive the disease. Other primary screening options include feces-based tests or colonoscopy. The 5-year survival rate for colorectal cancer is 64%.
While highly accurate at detecting DNA shed by tumors during treatable stages of colorectal cancer, the Shield test was not as effective at detecting precancerous areas of tissue, which are typically removed after being detected.
In its news release, Guardant Health officials said they anticipate the test to be covered under Medicare. The out-of-pocket cost for people whose insurance does not cover the test has not yet been announced. The test is expected to be available by next week, The New York Times reported.
If someone’s Shield test comes back positive, the person would then get more tests to confirm the result. Shield was shown in trials to have a 10% false positive rate.
“I was in for a routine physical, and my doctor asked when I had my last colonoscopy,” said John Gormly, a 77-year-old business executive in Newport Beach, California, according to a Guardant Health news release. “I said it’s been a long time, so he offered to give me the Shield blood test. A few days later, the result came back positive, so he referred me for a colonoscopy. It turned out I had stage II colon cancer. The tumor was removed, and I recovered very quickly. Thank God I had taken that blood test.”
A version of this article appeared on WebMD.com.
Risk Stratification May Work Well for FIT-Based CRC Screening in Elderly
WASHINGTON — , according to a study presented at the annual Digestive Disease Week® (DDW).
In particular, interval CRC risk can vary substantially based on the fecal hemoglobin (f-Hb) concentration in the patient’s last fecal immunochemical test (FIT), as well as the number of prior screening rounds.
“Less is known about what happens after the upper age limit has been reached and individuals are not invited to participate in more screening rounds. This is important as life expectancy is increasing, and it is increasingly important to consider the most efficient way of screening the elderly,” said lead author Brenda van Stigt, a PhD candidate focused on cancer screening at Erasmus University Medical Center in Rotterdam, the Netherlands.
In the Netherlands, adults between ages 55 and 75 are invited to participate in stool-based CRC screening every 2 years. Based on a fecal immunochemical testing (FIT) threshold of 47 μg Hb/g, those who test positive are referred to colonoscopy, and those who test negative are invited to participate again after a 2-year period.
FIT can play a major role in risk stratification, Ms. van Stigt noted, along with other factors that influence CRC risk, such as age, sex, and CRC screening history. Although this is documented for ages 55-75, she and colleagues wanted to know more about what happens after age 75.
Ms. Van Stigt and colleagues conducted a population-based study by analyzing Dutch national cancer registry data and FIT results around the final screening at age 75, looking at those who were diagnosed with CRC within 24 months of their last negative FIT. The researchers assessed interval CRC risk and cancer stage, accounting for sex, last f-Hb concentration, and the number of screening rounds.
Among 305,761 people with a complete 24-month follow-up after a negative FIT, 661 patients were diagnosed with interval CRC, indicating an overall interval CRC risk of 21.6 per 10,000 individuals with a negative FIT. There were no significant differences by sex.
However, there were differences by screening rounds, with those who had participated in three or four screening rounds having a lower risk than those who participated only once (HR, .49).
In addition, those with detectable f-Hb (>0 μg Hb/g) in their last screening round had a much higher interval CRC risk (HR, 4.87), at 65.8 per 10,000 negative FITs, compared with 13.8 per 10,000 among those without detectable f-Hb. Interval CRC risk also increased over time for those with detectable f-Hb.
About 15% of the total population had detectable f-Hb, whereas 46% of those with interval CRC had detectable f-Hb, Ms. van Stigt said, meaning that nearly half of patients who were diagnosed with interval CRC already had detectable f-Hb in their prior FIT.
In a survival analysis, there was no association between interval CRC risk and sex. However, those who participated in three or four screening rounds were half as likely to be diagnosed than those who participated once or twice, and those with detectable f-Hb were five times as likely to be diagnosed.
For late-stage CRC, there was no association with sex or the number of screening rounds. Detectable f-Hb was associated with not only a higher risk of interval CRC but also a late-stage diagnosis.
“These findings indicate that one uniform age to stop screening is suboptimal,” Ms. van Stigt said. “Personalized screening strategies should, therefore, also ideally incorporate a risk-stratified age to stop screening.”
The US Preventive Services Task Force recommends that clinicians personalize screening for ages 76-85, accounting for overall health, prior screening history, and patient preferences.
“But we have no clear guidance on how to quantify or weigh these factors. This interesting study highlights how one of these factors (prior screening history) and fecal hemoglobin level (an emerging factor) are powerful stratifiers of subsequent colorectal cancer risk,” said Sameer D. Saini, MD, AGAF, director and research investigator at the VA Ann Arbor Healthcare System’s Center for Clinical Management Research. Dr. Saini wasn’t involved with the study.
At the clinical level, Dr. Saini said, sophisticated modeling is needed to understand the interaction with competing risks and identify the optimal screening strategies for patients at varying levels of cancer risk and life expectancy. Models could also help to quantify the population benefits and cost-effectiveness of personalized screening.
“Finally, it is important to note that, in many health systems, access to quantitative FIT may be limited,” he said. “These data may be less informative if colonoscopy is the primary mode of screening.”
Ms. van Stigt and Dr. Saini reported no relevant disclosures.
WASHINGTON — , according to a study presented at the annual Digestive Disease Week® (DDW).
In particular, interval CRC risk can vary substantially based on the fecal hemoglobin (f-Hb) concentration in the patient’s last fecal immunochemical test (FIT), as well as the number of prior screening rounds.
“Less is known about what happens after the upper age limit has been reached and individuals are not invited to participate in more screening rounds. This is important as life expectancy is increasing, and it is increasingly important to consider the most efficient way of screening the elderly,” said lead author Brenda van Stigt, a PhD candidate focused on cancer screening at Erasmus University Medical Center in Rotterdam, the Netherlands.
In the Netherlands, adults between ages 55 and 75 are invited to participate in stool-based CRC screening every 2 years. Based on a fecal immunochemical testing (FIT) threshold of 47 μg Hb/g, those who test positive are referred to colonoscopy, and those who test negative are invited to participate again after a 2-year period.
FIT can play a major role in risk stratification, Ms. van Stigt noted, along with other factors that influence CRC risk, such as age, sex, and CRC screening history. Although this is documented for ages 55-75, she and colleagues wanted to know more about what happens after age 75.
Ms. Van Stigt and colleagues conducted a population-based study by analyzing Dutch national cancer registry data and FIT results around the final screening at age 75, looking at those who were diagnosed with CRC within 24 months of their last negative FIT. The researchers assessed interval CRC risk and cancer stage, accounting for sex, last f-Hb concentration, and the number of screening rounds.
Among 305,761 people with a complete 24-month follow-up after a negative FIT, 661 patients were diagnosed with interval CRC, indicating an overall interval CRC risk of 21.6 per 10,000 individuals with a negative FIT. There were no significant differences by sex.
However, there were differences by screening rounds, with those who had participated in three or four screening rounds having a lower risk than those who participated only once (HR, .49).
In addition, those with detectable f-Hb (>0 μg Hb/g) in their last screening round had a much higher interval CRC risk (HR, 4.87), at 65.8 per 10,000 negative FITs, compared with 13.8 per 10,000 among those without detectable f-Hb. Interval CRC risk also increased over time for those with detectable f-Hb.
About 15% of the total population had detectable f-Hb, whereas 46% of those with interval CRC had detectable f-Hb, Ms. van Stigt said, meaning that nearly half of patients who were diagnosed with interval CRC already had detectable f-Hb in their prior FIT.
In a survival analysis, there was no association between interval CRC risk and sex. However, those who participated in three or four screening rounds were half as likely to be diagnosed than those who participated once or twice, and those with detectable f-Hb were five times as likely to be diagnosed.
For late-stage CRC, there was no association with sex or the number of screening rounds. Detectable f-Hb was associated with not only a higher risk of interval CRC but also a late-stage diagnosis.
“These findings indicate that one uniform age to stop screening is suboptimal,” Ms. van Stigt said. “Personalized screening strategies should, therefore, also ideally incorporate a risk-stratified age to stop screening.”
The US Preventive Services Task Force recommends that clinicians personalize screening for ages 76-85, accounting for overall health, prior screening history, and patient preferences.
“But we have no clear guidance on how to quantify or weigh these factors. This interesting study highlights how one of these factors (prior screening history) and fecal hemoglobin level (an emerging factor) are powerful stratifiers of subsequent colorectal cancer risk,” said Sameer D. Saini, MD, AGAF, director and research investigator at the VA Ann Arbor Healthcare System’s Center for Clinical Management Research. Dr. Saini wasn’t involved with the study.
At the clinical level, Dr. Saini said, sophisticated modeling is needed to understand the interaction with competing risks and identify the optimal screening strategies for patients at varying levels of cancer risk and life expectancy. Models could also help to quantify the population benefits and cost-effectiveness of personalized screening.
“Finally, it is important to note that, in many health systems, access to quantitative FIT may be limited,” he said. “These data may be less informative if colonoscopy is the primary mode of screening.”
Ms. van Stigt and Dr. Saini reported no relevant disclosures.
WASHINGTON — , according to a study presented at the annual Digestive Disease Week® (DDW).
In particular, interval CRC risk can vary substantially based on the fecal hemoglobin (f-Hb) concentration in the patient’s last fecal immunochemical test (FIT), as well as the number of prior screening rounds.
“Less is known about what happens after the upper age limit has been reached and individuals are not invited to participate in more screening rounds. This is important as life expectancy is increasing, and it is increasingly important to consider the most efficient way of screening the elderly,” said lead author Brenda van Stigt, a PhD candidate focused on cancer screening at Erasmus University Medical Center in Rotterdam, the Netherlands.
In the Netherlands, adults between ages 55 and 75 are invited to participate in stool-based CRC screening every 2 years. Based on a fecal immunochemical testing (FIT) threshold of 47 μg Hb/g, those who test positive are referred to colonoscopy, and those who test negative are invited to participate again after a 2-year period.
FIT can play a major role in risk stratification, Ms. van Stigt noted, along with other factors that influence CRC risk, such as age, sex, and CRC screening history. Although this is documented for ages 55-75, she and colleagues wanted to know more about what happens after age 75.
Ms. Van Stigt and colleagues conducted a population-based study by analyzing Dutch national cancer registry data and FIT results around the final screening at age 75, looking at those who were diagnosed with CRC within 24 months of their last negative FIT. The researchers assessed interval CRC risk and cancer stage, accounting for sex, last f-Hb concentration, and the number of screening rounds.
Among 305,761 people with a complete 24-month follow-up after a negative FIT, 661 patients were diagnosed with interval CRC, indicating an overall interval CRC risk of 21.6 per 10,000 individuals with a negative FIT. There were no significant differences by sex.
However, there were differences by screening rounds, with those who had participated in three or four screening rounds having a lower risk than those who participated only once (HR, .49).
In addition, those with detectable f-Hb (>0 μg Hb/g) in their last screening round had a much higher interval CRC risk (HR, 4.87), at 65.8 per 10,000 negative FITs, compared with 13.8 per 10,000 among those without detectable f-Hb. Interval CRC risk also increased over time for those with detectable f-Hb.
About 15% of the total population had detectable f-Hb, whereas 46% of those with interval CRC had detectable f-Hb, Ms. van Stigt said, meaning that nearly half of patients who were diagnosed with interval CRC already had detectable f-Hb in their prior FIT.
In a survival analysis, there was no association between interval CRC risk and sex. However, those who participated in three or four screening rounds were half as likely to be diagnosed than those who participated once or twice, and those with detectable f-Hb were five times as likely to be diagnosed.
For late-stage CRC, there was no association with sex or the number of screening rounds. Detectable f-Hb was associated with not only a higher risk of interval CRC but also a late-stage diagnosis.
“These findings indicate that one uniform age to stop screening is suboptimal,” Ms. van Stigt said. “Personalized screening strategies should, therefore, also ideally incorporate a risk-stratified age to stop screening.”
The US Preventive Services Task Force recommends that clinicians personalize screening for ages 76-85, accounting for overall health, prior screening history, and patient preferences.
“But we have no clear guidance on how to quantify or weigh these factors. This interesting study highlights how one of these factors (prior screening history) and fecal hemoglobin level (an emerging factor) are powerful stratifiers of subsequent colorectal cancer risk,” said Sameer D. Saini, MD, AGAF, director and research investigator at the VA Ann Arbor Healthcare System’s Center for Clinical Management Research. Dr. Saini wasn’t involved with the study.
At the clinical level, Dr. Saini said, sophisticated modeling is needed to understand the interaction with competing risks and identify the optimal screening strategies for patients at varying levels of cancer risk and life expectancy. Models could also help to quantify the population benefits and cost-effectiveness of personalized screening.
“Finally, it is important to note that, in many health systems, access to quantitative FIT may be limited,” he said. “These data may be less informative if colonoscopy is the primary mode of screening.”
Ms. van Stigt and Dr. Saini reported no relevant disclosures.
FROM DDW 2024
We’re Making Progress in the Fight Against GI Cancers
The House Appropriations Committee has included AGA-provided language on gastric and esophageal cancers in the FY25 Labor, Health, and Human Services report.
Gastric and esophageal cancers rates are rising and have a low 5-year survival rate and are highly fatal due to the lack of screening — despite both cancers typically being associated with reduced mortality. Delays in diagnosis lead to poor prognoses when the cancer is already at an advanced stage.
These cancers receive disproportionately low funding and have the lowest ratio of funding to lethality to any other cancer.
That’s why it’s crucial to close the gap and increase screening for GI cancers that are less commonly screened for.
AGA’s provided language encourages NIH to develop, test and implement screening strategies for gastric and esophageal cancers using non-endoscopic screening modalities, personalized clinical risk stratification for screenings and biomarker-based risk-stratification.
Why is this important?
This submission is the first time AGA language on gastric and esophageal cancer has been requested and included in the committee’s report. This illustrates the Committee’s recognition of the importance of GI cancer detection and the work being done by NIH.
What does this mean for GI?
This is an important first step to increasing access to cancer screenings! We look forward to working with our champions on Capitol Hill to increase patient access GI cancer screenings.
The House Appropriations Committee has included AGA-provided language on gastric and esophageal cancers in the FY25 Labor, Health, and Human Services report.
Gastric and esophageal cancers rates are rising and have a low 5-year survival rate and are highly fatal due to the lack of screening — despite both cancers typically being associated with reduced mortality. Delays in diagnosis lead to poor prognoses when the cancer is already at an advanced stage.
These cancers receive disproportionately low funding and have the lowest ratio of funding to lethality to any other cancer.
That’s why it’s crucial to close the gap and increase screening for GI cancers that are less commonly screened for.
AGA’s provided language encourages NIH to develop, test and implement screening strategies for gastric and esophageal cancers using non-endoscopic screening modalities, personalized clinical risk stratification for screenings and biomarker-based risk-stratification.
Why is this important?
This submission is the first time AGA language on gastric and esophageal cancer has been requested and included in the committee’s report. This illustrates the Committee’s recognition of the importance of GI cancer detection and the work being done by NIH.
What does this mean for GI?
This is an important first step to increasing access to cancer screenings! We look forward to working with our champions on Capitol Hill to increase patient access GI cancer screenings.
The House Appropriations Committee has included AGA-provided language on gastric and esophageal cancers in the FY25 Labor, Health, and Human Services report.
Gastric and esophageal cancers rates are rising and have a low 5-year survival rate and are highly fatal due to the lack of screening — despite both cancers typically being associated with reduced mortality. Delays in diagnosis lead to poor prognoses when the cancer is already at an advanced stage.
These cancers receive disproportionately low funding and have the lowest ratio of funding to lethality to any other cancer.
That’s why it’s crucial to close the gap and increase screening for GI cancers that are less commonly screened for.
AGA’s provided language encourages NIH to develop, test and implement screening strategies for gastric and esophageal cancers using non-endoscopic screening modalities, personalized clinical risk stratification for screenings and biomarker-based risk-stratification.
Why is this important?
This submission is the first time AGA language on gastric and esophageal cancer has been requested and included in the committee’s report. This illustrates the Committee’s recognition of the importance of GI cancer detection and the work being done by NIH.
What does this mean for GI?
This is an important first step to increasing access to cancer screenings! We look forward to working with our champions on Capitol Hill to increase patient access GI cancer screenings.
Esophageal Cancer Risk Unchanged After Helicobacter Eradication
This finding suggests that eradication of H pylori is safe with regard to esophageal cancer risk, and eradication campaigns are not contributing to the rising incidence of esophageal adenocarcinoma (EAC) over the past four decades, reported lead author Anna-Klara Wiklund, MD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.“The decreased risk of esophageal adenocarcinoma seen in individuals with H pylori infection is probably explained by the H pylori–induced gastric atrophy, which reduces gastric acid production and thus acidic gastroesophageal reflux, the main risk factor for this tumor,” the investigators wrote in Gastroenterology. “It seems plausible that eradication of H pylori would increase the risk of EAC, although the answer to this question is unknown with the only study on the topic (from our group) having too few cases and too short follow-up.”
That study involved only 11 cases of EAC.
For the present study, Dr. Wiklund and colleagues aggregated data from all individuals who had undergone H pylori eradication in Finland, Denmark, Iceland, Norway, and Sweden from 1995 to 2019. The dataset comprised 661,987 such individuals with more than 5 million person-years after eradication therapy, including 550 cases of EAC. Median follow-up time was approximately 8 years, ranging from 1 to 24 years.
Analyzing these data revealed that standardized incidence ratio (SIR) of EAC was not increased after eradication therapy (0.89; 95% CI, 0.82-0.97). In fact, SIR decreased over time after eradication, reaching as low as 0.73 (95% CI, 0.61-0.86) during the follow-up period of 11-24 years. These findings were maintained regardless of age or sex, and within country-by-country analyses.
SIR for esophageal squamous cell carcinoma, which was calculated for comparison, showed no association with eradication therapy (0.99; 95% CI, 0.89-1.11).
“This study found no evidence supporting the hypothesis of a gradually increasing risk of esophageal adenocarcinoma over time after H pylori eradication treatment,” the investigators wrote.
Other risks were detected, including an overall increased SIR of EAC observed among participants with gastroesophageal reflux disease (GERD) and those using long-term proton pump inhibitors (PPIs). These were expected, however, “considering the strong and well-established association with EAC.”
Dr. Wiklund and colleagues suggested that more studies are needed to confirm their findings, although the present data provide confidence that H pylori eradication does not raise risk of EAC.
“This is valuable knowledge when considering eradication treatment for individual patients and eradication programs in high-risk populations of gastric cancer,” they wrote. “The results should be generalizable to other high-income countries with low prevalence of H pylori and high incidence of EAC, but studies from other regions with different patterns of these conditions are warranted.”
They also called for more basic research to understand why eradicating H pylori does not lead to an increased risk of EAC.The study was supported by Sjoberg Foundation, Nordic Cancer Union, Stockholm County Council, Stockholm Cancer Society. Investigators disclosed no conflicts of interest.
Understanding the demographic and biomarker risk predictors of esophageal cancer continues to be a research priority. Many esophageal cancer patients fall outside of current screening guidelines. Updated recommendations have suggested including high risk-women, driven by higher quality datasets, emerging biomarkers, and cost effective non-endoscopic screening devices.
In this article, Wiklund et al. challenge another dogma that Helicobacter pylori infection offers protection against esophageal cancer. More specifically that overtreatment of H pylori is associated with increased incidence of esophageal adenocarcinoma. Their Nordic data set identified 550 cases of esophageal cancer in the 661,987 patients treated for H pylori from 1995–2018 who were followed >5 million person-years. Interestingly, standardized incidence ratio of esophageal adenocarcinoma decreased over time.
This large dataset continues to encourage us to treat H pylori in patients at risk of progressing to gastric cancer. This parallels a growing fund of literature encouraging us to move away from the linear pathophysiologic logic that eliminating H pylori-induced gastric atrophy provokes gastroesophageal reflux disease and esophageal cancer. Instead we should factor in other parameters, including the complex interaction between the esophageal microbiome and gastric H pylori. Some postulated mechanisms include an extension of the gastric inflammatory milieu into the esophagus, and potential crosstalk with the esophageal microbiome.
Such studies underscore the need to personalize both foregut cancer screening criteria and treatment of inflammatory conditions at a patient and population level, so that we can make meaningful impacts in disease prevalence and cancer survival.
Fouad Otaki, MD, is associate professor in the Division of Gastroenterology & Hepatology at Oregon Health & Science University, Portland.
Understanding the demographic and biomarker risk predictors of esophageal cancer continues to be a research priority. Many esophageal cancer patients fall outside of current screening guidelines. Updated recommendations have suggested including high risk-women, driven by higher quality datasets, emerging biomarkers, and cost effective non-endoscopic screening devices.
In this article, Wiklund et al. challenge another dogma that Helicobacter pylori infection offers protection against esophageal cancer. More specifically that overtreatment of H pylori is associated with increased incidence of esophageal adenocarcinoma. Their Nordic data set identified 550 cases of esophageal cancer in the 661,987 patients treated for H pylori from 1995–2018 who were followed >5 million person-years. Interestingly, standardized incidence ratio of esophageal adenocarcinoma decreased over time.
This large dataset continues to encourage us to treat H pylori in patients at risk of progressing to gastric cancer. This parallels a growing fund of literature encouraging us to move away from the linear pathophysiologic logic that eliminating H pylori-induced gastric atrophy provokes gastroesophageal reflux disease and esophageal cancer. Instead we should factor in other parameters, including the complex interaction between the esophageal microbiome and gastric H pylori. Some postulated mechanisms include an extension of the gastric inflammatory milieu into the esophagus, and potential crosstalk with the esophageal microbiome.
Such studies underscore the need to personalize both foregut cancer screening criteria and treatment of inflammatory conditions at a patient and population level, so that we can make meaningful impacts in disease prevalence and cancer survival.
Fouad Otaki, MD, is associate professor in the Division of Gastroenterology & Hepatology at Oregon Health & Science University, Portland.
Understanding the demographic and biomarker risk predictors of esophageal cancer continues to be a research priority. Many esophageal cancer patients fall outside of current screening guidelines. Updated recommendations have suggested including high risk-women, driven by higher quality datasets, emerging biomarkers, and cost effective non-endoscopic screening devices.
In this article, Wiklund et al. challenge another dogma that Helicobacter pylori infection offers protection against esophageal cancer. More specifically that overtreatment of H pylori is associated with increased incidence of esophageal adenocarcinoma. Their Nordic data set identified 550 cases of esophageal cancer in the 661,987 patients treated for H pylori from 1995–2018 who were followed >5 million person-years. Interestingly, standardized incidence ratio of esophageal adenocarcinoma decreased over time.
This large dataset continues to encourage us to treat H pylori in patients at risk of progressing to gastric cancer. This parallels a growing fund of literature encouraging us to move away from the linear pathophysiologic logic that eliminating H pylori-induced gastric atrophy provokes gastroesophageal reflux disease and esophageal cancer. Instead we should factor in other parameters, including the complex interaction between the esophageal microbiome and gastric H pylori. Some postulated mechanisms include an extension of the gastric inflammatory milieu into the esophagus, and potential crosstalk with the esophageal microbiome.
Such studies underscore the need to personalize both foregut cancer screening criteria and treatment of inflammatory conditions at a patient and population level, so that we can make meaningful impacts in disease prevalence and cancer survival.
Fouad Otaki, MD, is associate professor in the Division of Gastroenterology & Hepatology at Oregon Health & Science University, Portland.
This finding suggests that eradication of H pylori is safe with regard to esophageal cancer risk, and eradication campaigns are not contributing to the rising incidence of esophageal adenocarcinoma (EAC) over the past four decades, reported lead author Anna-Klara Wiklund, MD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.“The decreased risk of esophageal adenocarcinoma seen in individuals with H pylori infection is probably explained by the H pylori–induced gastric atrophy, which reduces gastric acid production and thus acidic gastroesophageal reflux, the main risk factor for this tumor,” the investigators wrote in Gastroenterology. “It seems plausible that eradication of H pylori would increase the risk of EAC, although the answer to this question is unknown with the only study on the topic (from our group) having too few cases and too short follow-up.”
That study involved only 11 cases of EAC.
For the present study, Dr. Wiklund and colleagues aggregated data from all individuals who had undergone H pylori eradication in Finland, Denmark, Iceland, Norway, and Sweden from 1995 to 2019. The dataset comprised 661,987 such individuals with more than 5 million person-years after eradication therapy, including 550 cases of EAC. Median follow-up time was approximately 8 years, ranging from 1 to 24 years.
Analyzing these data revealed that standardized incidence ratio (SIR) of EAC was not increased after eradication therapy (0.89; 95% CI, 0.82-0.97). In fact, SIR decreased over time after eradication, reaching as low as 0.73 (95% CI, 0.61-0.86) during the follow-up period of 11-24 years. These findings were maintained regardless of age or sex, and within country-by-country analyses.
SIR for esophageal squamous cell carcinoma, which was calculated for comparison, showed no association with eradication therapy (0.99; 95% CI, 0.89-1.11).
“This study found no evidence supporting the hypothesis of a gradually increasing risk of esophageal adenocarcinoma over time after H pylori eradication treatment,” the investigators wrote.
Other risks were detected, including an overall increased SIR of EAC observed among participants with gastroesophageal reflux disease (GERD) and those using long-term proton pump inhibitors (PPIs). These were expected, however, “considering the strong and well-established association with EAC.”
Dr. Wiklund and colleagues suggested that more studies are needed to confirm their findings, although the present data provide confidence that H pylori eradication does not raise risk of EAC.
“This is valuable knowledge when considering eradication treatment for individual patients and eradication programs in high-risk populations of gastric cancer,” they wrote. “The results should be generalizable to other high-income countries with low prevalence of H pylori and high incidence of EAC, but studies from other regions with different patterns of these conditions are warranted.”
They also called for more basic research to understand why eradicating H pylori does not lead to an increased risk of EAC.The study was supported by Sjoberg Foundation, Nordic Cancer Union, Stockholm County Council, Stockholm Cancer Society. Investigators disclosed no conflicts of interest.
This finding suggests that eradication of H pylori is safe with regard to esophageal cancer risk, and eradication campaigns are not contributing to the rising incidence of esophageal adenocarcinoma (EAC) over the past four decades, reported lead author Anna-Klara Wiklund, MD, of Karolinska Institutet, Stockholm, Sweden, and colleagues.“The decreased risk of esophageal adenocarcinoma seen in individuals with H pylori infection is probably explained by the H pylori–induced gastric atrophy, which reduces gastric acid production and thus acidic gastroesophageal reflux, the main risk factor for this tumor,” the investigators wrote in Gastroenterology. “It seems plausible that eradication of H pylori would increase the risk of EAC, although the answer to this question is unknown with the only study on the topic (from our group) having too few cases and too short follow-up.”
That study involved only 11 cases of EAC.
For the present study, Dr. Wiklund and colleagues aggregated data from all individuals who had undergone H pylori eradication in Finland, Denmark, Iceland, Norway, and Sweden from 1995 to 2019. The dataset comprised 661,987 such individuals with more than 5 million person-years after eradication therapy, including 550 cases of EAC. Median follow-up time was approximately 8 years, ranging from 1 to 24 years.
Analyzing these data revealed that standardized incidence ratio (SIR) of EAC was not increased after eradication therapy (0.89; 95% CI, 0.82-0.97). In fact, SIR decreased over time after eradication, reaching as low as 0.73 (95% CI, 0.61-0.86) during the follow-up period of 11-24 years. These findings were maintained regardless of age or sex, and within country-by-country analyses.
SIR for esophageal squamous cell carcinoma, which was calculated for comparison, showed no association with eradication therapy (0.99; 95% CI, 0.89-1.11).
“This study found no evidence supporting the hypothesis of a gradually increasing risk of esophageal adenocarcinoma over time after H pylori eradication treatment,” the investigators wrote.
Other risks were detected, including an overall increased SIR of EAC observed among participants with gastroesophageal reflux disease (GERD) and those using long-term proton pump inhibitors (PPIs). These were expected, however, “considering the strong and well-established association with EAC.”
Dr. Wiklund and colleagues suggested that more studies are needed to confirm their findings, although the present data provide confidence that H pylori eradication does not raise risk of EAC.
“This is valuable knowledge when considering eradication treatment for individual patients and eradication programs in high-risk populations of gastric cancer,” they wrote. “The results should be generalizable to other high-income countries with low prevalence of H pylori and high incidence of EAC, but studies from other regions with different patterns of these conditions are warranted.”
They also called for more basic research to understand why eradicating H pylori does not lead to an increased risk of EAC.The study was supported by Sjoberg Foundation, Nordic Cancer Union, Stockholm County Council, Stockholm Cancer Society. Investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
How Aspirin May Lower Risk for Colorectal Cancer
A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.
The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.
But what, exactly, is aspirin doing?
We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.
“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.
In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.
Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.
Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.
The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).
Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.
The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.
At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.
Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.
The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.
CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.
The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.
“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”
Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.
However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.
PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.
“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”
David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.
Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.
Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.
A version of this article appeared on Medscape.com .
A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.
The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.
But what, exactly, is aspirin doing?
We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.
“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.
In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.
Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.
Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.
The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).
Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.
The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.
At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.
Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.
The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.
CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.
The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.
“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”
Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.
However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.
PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.
“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”
David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.
Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.
Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.
A version of this article appeared on Medscape.com .
A 2020 meta-analysis, for instance, found that 325 mg of daily aspirin — the typical dose in a single tablet — conferred a 35% reduced risk of developing CRC, and a highly cited The Lancet study from 2010 found that a low dose of daily aspirin reduced the incidence of colon cancer by 24% and colon cancer deaths by 35% over 20 years.
The evidence surrounding aspirin and CRC is so intriguing that more than 70,000 people are currently participating in more than two dozen clinical studies worldwide, putting aspirin through its paces as an intervention in CRC.
But what, exactly, is aspirin doing?
We know that aspirin inhibits cyclooxygenase (COX) enzymes — COX-1 and COX-2, specifically — and that the COX-2 pathway is implicated in the development and progression of CRC, explained Marco Scarpa, MD, PhD, staff surgeon at the University of Padova in Padova, Italy.
“However, the new thing we’ve found is that aspirin may have a direct role in enhancing immunosurveillance,” Dr. Scarpa said in an interview.
In April, Dr. Scarpa’s team published a paper in Cancer describing a mechanism that provides deeper insight into the aspirin-CRC connection.
Dr. Scarpa heads up the IMMUNOREACT study group, a collaboration of dozens of researchers across Italy running studies on immunosurveillance in rectal cancer. In the baseline study, IMMUNOREACT 1, the team created and analyzed a database of records from 238 patients who underwent surgery for CRC at the Azienda Ospedale Università di Padova, Padova, Italy, from 2015 to 2019.
Using the same database, the latest findings from IMMUNOREACT 7 focused on the fate of the 31 patients (13%) who used aspirin regularly.
The researchers found that regular aspirin use did not appear to affect colorectal tumor stage at diagnosis, but tumor grading was significantly lower overall, especially in patients with BRAF mutations. Regular aspirin users were also less likely to have nodal metastases and metastatic lymph nodes, and this effect was more pronounced in patients with proximal (right-sided) colon cancer vs distal (left-sided).
Most notably, IMMUNOREACT 7 revealed that aspirin has beneficial effects on the CRC immune microenvironment.
The team found that aspirin directly boosts the presence of antigens on gastrointestinal epithelial tumor cells, which can direct the body’s immune response to combat the cancer.
At a macro level, the aspirin users in the study were more likely to have high levels of tumor-infiltrating lymphocytes (TILs). Dr. Scarpa’s team had previously shown that high levels of CD8+ and CD3+ TILs were predictive of successful neoadjuvant therapy in rectal cancer.
Cytotoxic CD8+ T cells are central to the anticancer immune response, and in the latest study, a high ratio of CD8+/CD3+ T cells was more common in aspirin users, suggesting a stronger presence of cancer-killing CD8+ cells. Expression of CD8 beta+, an activation marker of CD8+ cells, was also enhanced in aspirin users.
The most significant discovery, according to Dr. Scarpa, was that aspirin users were more likely to show high expression of CD80 on the surface of their rectal epithelial cells.
CD80 is a molecule that allows T cells to identify the tumor cell as foreign and kill it. Although cancer cells can downregulate their CD80 to avoid detection by T cells, the study suggests that aspirin appears to help foil this strategy by boosting the production of CD80 on the surface of the tumor cells.
The researchers confirmed the clinical findings by showing that aspirin increased CD80 gene expression in lab-cultivated CRC cells.
“We didn’t expect the activation through CD80,” said Dr. Scarpa. “This means that aspirin can act on this very first interaction between the epithelial cell and the CD8+ lymphocyte.”
Overall, these new data suggest that aspirin helps activate the immune system, which helps explain its potential chemopreventive effect in CRC.
However, one puzzling result was that aspirin boosted expression of PD-L1 genes in the CRC cells, said Joanna Davies, DPhil, an immunologist who heads up the San Diego Biomedical Research Institute, San Diego, California, and was not involved in the study.
PD-L1 serves as an “off” switch for patrolling T cells, which protects the tumor cell from being recognized.
“If aspirin is inducing PD-L1 on cancer cells, that is a potential problem,” said Dr. Davies. “An ideal therapy might be the combination of aspirin to enhance the CD8 T cells in the tumor and immune checkpoint blockade to block PD-L1.”
David Kerr, CBE, MD, DSc, agreed that high-dose aspirin plus immunotherapy might be “a wee bit more effective.” However, the combination would be blocked by the economics of drug development: “Will anybody ever do a trial of 10,000 patients to prove that? Not on your nelly,” said Dr. Kerr, professor of cancer medicine at the University of Oxford, Oxford, England.
Despite the small patient numbers in the study, Dr. Kerr felt encouraged by the IMMUNOREACT analysis. “It’s a plausible piece of science and some quite promising work on the tumor immune microenvironment and the effects of aspirin on it,” Dr. Kerr said in a recent commentary for this news organization.
Dr. Scarpa and Dr. Davies had no conflicts of interest to declare.
A version of this article appeared on Medscape.com .
Should ctDNA guide clinical decisions in GI cancers?
CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.
Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.
However, ctDNA’s role in guiding clinical decisions is still being defined.
The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
DYNAMIC Trial Results
Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.
Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.
At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.
Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).
Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).
“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
DYNAMIC-Pancreas Study Results
In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.
At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.
Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.
In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.
“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”
The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.
“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”
But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.
Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”
Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.
Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”
Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.
Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.
CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.
Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.
However, ctDNA’s role in guiding clinical decisions is still being defined.
The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
DYNAMIC Trial Results
Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.
Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.
At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.
Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).
Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).
“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
DYNAMIC-Pancreas Study Results
In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.
At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.
Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.
In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.
“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”
The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.
“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”
But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.
Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”
Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.
Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”
Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.
Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.
CHICAGO – Circulating tumor DNA (ctDNA), or DNA shed from tumors that is detected in the bloodstream, has shown increasing promise as a prognostic tool in gastrointestinal cancers, allowing investigators to make real-time assessments of treatment response and the likelihood of recurrence.
Depending on the type of assay and analysis used, ctDNA can provide a wealth of information about cancer genetic variants. ctDNA assays can be used for primary screening, to track tumor burden, or to detect minimal residual disease (MRD) after cancer surgery.
However, ctDNA’s role in guiding clinical decisions is still being defined.
The same group also presented exploratory findings showing that positive ctDNA is a significant predictor of recurrence in people with early-stage pancreatic cancer following surgery. However, the investigators concluded, ctDNA status should not be used to inform treatment decisions concerning duration of adjuvant chemotherapy in these patients.
DYNAMIC Trial Results
Jeanne Tie, MD, of the Peter MacCallum Cancer Centre in Melbourne, presented 5-year survival results at ASCO from the DYNAMIC randomized controlled trial, whose 2-year findings had already shown ctDNA to be helpful in stratifying stage II colon cancer patients for adjuvant chemotherapy or no treatment.
Because surgery is curative in 80% of these patients, it is important to identify the minority that will need chemotherapy, Dr. Tie said.
At 5 years’ follow-up, Dr. Tie reported, patients randomized to a ctDNA-guided approach (negative ctDNA post surgery resulted in no treatment, and positive ctDNA led to adjuvant chemotherapy) did not see differences in overall survival compared with conventionally managed patients, who received chemotherapy at the clinician’s discretion.
Among ctDNA-guided patients in the study (n = 302), 5-year overall survival was 93.8%. For conventionally managed patients (n = 153), overall survival was 93.3% at 5 years (hazard ratio [HR], 1.05; 95% CI, 0.47-2.37; P = .887).
Further, the researchers found that a high ctDNA clearance rate was achieved with adjuvant chemotherapy in postoperative patients who were ctDNA positive. And 5-year recurrence rates were markedly lower in patients who achieved ctDNA clearance, compared with those who did not: 85.2% vs 20% (HR, 15.4; 95% CI, 3.91-61.0; P < .001).
“This approach of only treating patients with a positive ctDNA achieved excellent survival outcomes, including in patients with T4 disease. A high ctDNA clearance rate can be achieved with adjuvant chemotherapy, and this in turn was associated with favorable outcomes,” Dr. Tie said during the meeting. “And finally, the precision of the ctDNA approach may be further refined by increasing [the number of genetic variants] tracked and by incorporating ctDNA molecular burden. However, these findings will require further validation.”
DYNAMIC-Pancreas Study Results
In a separate presentation during the same session, Belinda Lee, MD, also of the Peter MacCallum Cancer Centre, showed results from the DYNAMIC-Pancreas study, which looked at ctDNA testing a median 5 weeks after surgery in 102 people with early-stage (Eastern Cooperative Oncology Group 0-1) pancreatic cancer. Patients who were ctDNA positive received 6 months of adjuvant chemotherapy of the physician’s choice (FOLFIRINOX or gemcitabine/capecitabine) while those who were ctDNA negative after surgery had the option to de-escalate to 3 months of chemotherapy treatment at the physician’s discretion.
At a median 3 years’ follow-up, Dr. Lee and colleagues found that the median recurrence-free survival was 13 months for patients who were ctDNA positive after surgery and 22 months for those who were ctDNA negative (HR, 0.52; P = .003), showing that positive ctDNA is prognostic of earlier recurrence independent of other factors.
Dr. Lee said that, given the high recurrence risk also seen in ctDNA-negative patients, reducing duration of chemotherapy was not recommended based on ctDNA-negative status.
In an interview, Stacey Cohen, MD, of Fred Hutch Cancer Center in Seattle, Washington, the discussant on the two presentations at ASCO, said that, until these results are further validated in stage II colon cancer patients,t it is unlikely that they will change clinical practice guidelines.
“They did an amazing job,” Dr. Cohen said of the researchers. “They’re at the forefront of the field of actually doing prospective analysis. And yet there are still some gaps that are missing in our understanding.”
The assays used in both studies, Dr. Cohen noted, are used only in research and are not available commercially in the United States. That, plus the fact that physicians were allowed to choose between chemotherapy regimens, made it harder to parse the results.
“Provider choice increases bias,” Dr. Cohen said. “And I think that’s the problem of having two chemo regimens to choose from, or in the case of the colon cancer trial, not selecting whether patients got a single chemotherapy agent or a doublet. These are pretty big differences.”
But the field is moving quickly, “and it is an exciting time to improve patient selection for chemotherapy treatment,” she continued.
Allowing physicians to choose chemotherapy regimens reflected real-world clinical practice, “especially given that this study is designed to test a strategy rather than a specific treatment, said Dr. Tie in an interview. “More work will need to be done to specifically address the question of which chemotherapy regimen is more effective to treat ctDNA-positive disease.”
Dr. Cohen noted that, while evidence is mounting to support the value of ctDNA in colon cancer, there is far less evidence for pancreatic cancer.
Dr. Lee and colleagues’ study “adds to the literature, and I think what it teaches us is that ctDNA remains a prognostic risk factor,” she said. “But we saw that even patients who are negative have a high recurrence risk. So we’re not ready to act on it yet. As with the colon cancer study, different chemotherapy regimens were used, and for different time lengths.”
Whether in colon cancer or pancreatic cancer, ctDNA results, “are highly tied to which assay you’re using and which scenario you’re testing them in,” Dr. Cohen said.
Dr. Tie and colleagues’ study was sponsored by her institution, with additional funding received from the Australian government, the National Institutes of Health, and other foundations. She disclosed speaking and/or consulting fees from Haystack Oncology, Amgen, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca, and others. Dr. Lee’s study was sponsored by the Marcus Foundation. She disclosed receiving honoraria from Roche. Dr. Cohen reported no conflicts of interest.
FROM ASCO 2024
AI Patient Navigator Helps Re-Engage Underserved Patients After Missed Colonoscopy
A conversational artificial intelligence patient navigator was successful at re-engaging patients in colonoscopy screening, essentially doubling the colonoscopy completion rate in patients from underserved communities who had previously missed or avoided an appointment, a new analysis found.
Colorectal cancer (CRC) disparities among people of color in the United States are well documented, Alyson Moadel, PhD, told the audience during a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.
Compared with White people, Black individuals have a 20% higher incidence of CRC and are 40% more likely to die from the disease. In addition, cases of early-onset CRC are rising more rapidly in Hispanic and Latinx populations than in other racial/ethnic groups, explained Dr. Moadel, deputy director of community engagement and cancer health equity at Montefiore Einstein Comprehensive Cancer Center, New York.
Despite active outreach by professional patient navigators at Montefiore — which primarily serves people from communities of color and low-income households — 59% of 3276 patients either canceled or did not show up for their colonoscopy in 2022. Only 21% of this group completed the procedure.
This led Dr. Moadel and her team to test the ability of the MyEleanor AI patient navigator to re-engage 2400 English- and Spanish-speaking patients who were nonadherent with colonoscopy appointments.
The MyEleanor AI navigator called patients to discuss rescheduling, assess barriers to colonoscopy uptake, offer live transfers to clinical staff to reschedule appointments, and provide procedure preparation reminder calls.
The AI navigator followed this patient-friendly script: “I’m Eleanor, the automated care assistant for your team at Montefiore. I am calling today because we noticed that you missed your most recent colonoscopy appointment, and we would like to help you reschedule it at the end of this call.”
What’s “very exciting,” said Dr. Moadel, is that more than half — 57% (1368 of the 2400 patients) — actually had a conversation with MyEleanor, some lasting up to 9 minutes.
Of the patients who engaged with the AI navigator, 58% (789 of 1368) accepted live transfer to a staff member to reschedule their appointment, and 25% of these patients completed their colonoscopy screening.
The no-show completion rate nearly doubled from 10% to 19%, and patient volume for colonoscopies increased by 36%.
Patients also reported barriers to screening, which included transportation (38%), no perceived need (36%), time constraints (36%), lack of prompting from their doctor (33%), and medical mistrust (32%), as well as concerns about findings from the screening (28%) and cost (27%).
Dr. Moadel said next steps include measuring the impact of MyEleanor on patient navigator burden, patient satisfaction, and cost savings, and testing it in other screening programs such as lung and breast.
Using AI to Deliver More Equitable Cancer Care
“Overall, this quality improvement initiative is a truly innovative means of increasing cancer screening,” Fumiko Chino, MD, with Memorial Sloan Kettering Monmouth, in Middletown, New Jersey, told the briefing. “It really offloads the work from an overburdened health care workforce by leveraging AI to optimize the outreach capacity to vulnerable populations.”
Dr. Chino, who wasn’t involved in the project, said this work “delivers on the promise of technology to facilitate better, more efficient, more equitable cancer care, and I really anticipate that it will ultimately improve cancer outcomes.”
A key aspect to highlight, said Dr. Chino, is that the patients who conversed with MyEleanor were on average in their 50s, and three fourths were Black, Latinx, or Hispanic, “so the intervention really did work in the population at highest risk for screening gaps.”
Dr. Chino said it’s important to note that this was a quality improvement project, not a randomized control trial, and the AI navigator will need to be continually re-evaluated over time and tested in other populations.
The study had no specific funding. Dr. Moadel reports no relevant financial relationships. Several authors have relationships with the AI-enabled care management company MyndYou, which provides the MyEleanor AI navigator.
A version of this article appeared on Medscape.com.
A conversational artificial intelligence patient navigator was successful at re-engaging patients in colonoscopy screening, essentially doubling the colonoscopy completion rate in patients from underserved communities who had previously missed or avoided an appointment, a new analysis found.
Colorectal cancer (CRC) disparities among people of color in the United States are well documented, Alyson Moadel, PhD, told the audience during a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.
Compared with White people, Black individuals have a 20% higher incidence of CRC and are 40% more likely to die from the disease. In addition, cases of early-onset CRC are rising more rapidly in Hispanic and Latinx populations than in other racial/ethnic groups, explained Dr. Moadel, deputy director of community engagement and cancer health equity at Montefiore Einstein Comprehensive Cancer Center, New York.
Despite active outreach by professional patient navigators at Montefiore — which primarily serves people from communities of color and low-income households — 59% of 3276 patients either canceled or did not show up for their colonoscopy in 2022. Only 21% of this group completed the procedure.
This led Dr. Moadel and her team to test the ability of the MyEleanor AI patient navigator to re-engage 2400 English- and Spanish-speaking patients who were nonadherent with colonoscopy appointments.
The MyEleanor AI navigator called patients to discuss rescheduling, assess barriers to colonoscopy uptake, offer live transfers to clinical staff to reschedule appointments, and provide procedure preparation reminder calls.
The AI navigator followed this patient-friendly script: “I’m Eleanor, the automated care assistant for your team at Montefiore. I am calling today because we noticed that you missed your most recent colonoscopy appointment, and we would like to help you reschedule it at the end of this call.”
What’s “very exciting,” said Dr. Moadel, is that more than half — 57% (1368 of the 2400 patients) — actually had a conversation with MyEleanor, some lasting up to 9 minutes.
Of the patients who engaged with the AI navigator, 58% (789 of 1368) accepted live transfer to a staff member to reschedule their appointment, and 25% of these patients completed their colonoscopy screening.
The no-show completion rate nearly doubled from 10% to 19%, and patient volume for colonoscopies increased by 36%.
Patients also reported barriers to screening, which included transportation (38%), no perceived need (36%), time constraints (36%), lack of prompting from their doctor (33%), and medical mistrust (32%), as well as concerns about findings from the screening (28%) and cost (27%).
Dr. Moadel said next steps include measuring the impact of MyEleanor on patient navigator burden, patient satisfaction, and cost savings, and testing it in other screening programs such as lung and breast.
Using AI to Deliver More Equitable Cancer Care
“Overall, this quality improvement initiative is a truly innovative means of increasing cancer screening,” Fumiko Chino, MD, with Memorial Sloan Kettering Monmouth, in Middletown, New Jersey, told the briefing. “It really offloads the work from an overburdened health care workforce by leveraging AI to optimize the outreach capacity to vulnerable populations.”
Dr. Chino, who wasn’t involved in the project, said this work “delivers on the promise of technology to facilitate better, more efficient, more equitable cancer care, and I really anticipate that it will ultimately improve cancer outcomes.”
A key aspect to highlight, said Dr. Chino, is that the patients who conversed with MyEleanor were on average in their 50s, and three fourths were Black, Latinx, or Hispanic, “so the intervention really did work in the population at highest risk for screening gaps.”
Dr. Chino said it’s important to note that this was a quality improvement project, not a randomized control trial, and the AI navigator will need to be continually re-evaluated over time and tested in other populations.
The study had no specific funding. Dr. Moadel reports no relevant financial relationships. Several authors have relationships with the AI-enabled care management company MyndYou, which provides the MyEleanor AI navigator.
A version of this article appeared on Medscape.com.
A conversational artificial intelligence patient navigator was successful at re-engaging patients in colonoscopy screening, essentially doubling the colonoscopy completion rate in patients from underserved communities who had previously missed or avoided an appointment, a new analysis found.
Colorectal cancer (CRC) disparities among people of color in the United States are well documented, Alyson Moadel, PhD, told the audience during a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting.
Compared with White people, Black individuals have a 20% higher incidence of CRC and are 40% more likely to die from the disease. In addition, cases of early-onset CRC are rising more rapidly in Hispanic and Latinx populations than in other racial/ethnic groups, explained Dr. Moadel, deputy director of community engagement and cancer health equity at Montefiore Einstein Comprehensive Cancer Center, New York.
Despite active outreach by professional patient navigators at Montefiore — which primarily serves people from communities of color and low-income households — 59% of 3276 patients either canceled or did not show up for their colonoscopy in 2022. Only 21% of this group completed the procedure.
This led Dr. Moadel and her team to test the ability of the MyEleanor AI patient navigator to re-engage 2400 English- and Spanish-speaking patients who were nonadherent with colonoscopy appointments.
The MyEleanor AI navigator called patients to discuss rescheduling, assess barriers to colonoscopy uptake, offer live transfers to clinical staff to reschedule appointments, and provide procedure preparation reminder calls.
The AI navigator followed this patient-friendly script: “I’m Eleanor, the automated care assistant for your team at Montefiore. I am calling today because we noticed that you missed your most recent colonoscopy appointment, and we would like to help you reschedule it at the end of this call.”
What’s “very exciting,” said Dr. Moadel, is that more than half — 57% (1368 of the 2400 patients) — actually had a conversation with MyEleanor, some lasting up to 9 minutes.
Of the patients who engaged with the AI navigator, 58% (789 of 1368) accepted live transfer to a staff member to reschedule their appointment, and 25% of these patients completed their colonoscopy screening.
The no-show completion rate nearly doubled from 10% to 19%, and patient volume for colonoscopies increased by 36%.
Patients also reported barriers to screening, which included transportation (38%), no perceived need (36%), time constraints (36%), lack of prompting from their doctor (33%), and medical mistrust (32%), as well as concerns about findings from the screening (28%) and cost (27%).
Dr. Moadel said next steps include measuring the impact of MyEleanor on patient navigator burden, patient satisfaction, and cost savings, and testing it in other screening programs such as lung and breast.
Using AI to Deliver More Equitable Cancer Care
“Overall, this quality improvement initiative is a truly innovative means of increasing cancer screening,” Fumiko Chino, MD, with Memorial Sloan Kettering Monmouth, in Middletown, New Jersey, told the briefing. “It really offloads the work from an overburdened health care workforce by leveraging AI to optimize the outreach capacity to vulnerable populations.”
Dr. Chino, who wasn’t involved in the project, said this work “delivers on the promise of technology to facilitate better, more efficient, more equitable cancer care, and I really anticipate that it will ultimately improve cancer outcomes.”
A key aspect to highlight, said Dr. Chino, is that the patients who conversed with MyEleanor were on average in their 50s, and three fourths were Black, Latinx, or Hispanic, “so the intervention really did work in the population at highest risk for screening gaps.”
Dr. Chino said it’s important to note that this was a quality improvement project, not a randomized control trial, and the AI navigator will need to be continually re-evaluated over time and tested in other populations.
The study had no specific funding. Dr. Moadel reports no relevant financial relationships. Several authors have relationships with the AI-enabled care management company MyndYou, which provides the MyEleanor AI navigator.
A version of this article appeared on Medscape.com.
Autonomous AI Outperforms Humans in Optical Diagnosis of Colorectal Polyps
, while providing greater alignment with pathology-based surveillance intervals, based on a randomized controlled trial.
These findings suggest that autonomous AI may one day replace histologic assessment of diminutive polyps, reported lead author Roupen Djinbachian, MD, of the Montreal University Hospital Research Center, Montreal, Quebec, Canada, and colleagues.Optical diagnosis of diminutive colorectal polyps has been proposed as a cost-effective alternative to histologic diagnosis, but its implementation in general clinical practice has been hindered by endoscopists’ concerns about incorrect diagnoses, the investigators wrote in Gastroenterology.“AI-based systems (CADx) have been proposed as a solution to these barriers to implementation, with studies showing high adherence to Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds when using AI-H,” they wrote. “However, the efficacy and safety of autonomous AI-based diagnostic platforms have not yet been evaluated.”
To address this knowledge gap, Dr. Djinbachian and colleagues conducted a randomized controlled noninferiority trial involving 467 patients, all of whom underwent elective colonoscopies at a single academic institution.
Participants were randomly assigned to one of two groups. The first group received an optical diagnosis of diminutive (1-5 mm) colorectal polyps using an autonomous AI-based CADx system without any human input. The second group had diagnoses performed by endoscopists who used AI-H to make their optical diagnoses.
The primary outcome was the accuracy of optical diagnosis compared with the gold standard of histologic evaluation. Secondarily, the investigators explored associations between pathology-based surveillance intervals and various measures of accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
The results showed that the accuracy of optical diagnosis for diminutive polyps was similar between the two groups, supporting noninferiority. Autonomous AI achieved an accuracy rate of 77.2%, while the AI-H group had an accuracy of 72.1%, which was not statistically significant (P = .86).
But when it came to pathology-based surveillance intervals, autonomous AI showed a clear advantage; the autonomous AI system achieved a 91.5% agreement rate, compared with 82.1% for the AI-H group (P = .016).
“These findings indicate that autonomous AI not only matches but also surpasses AI-H in accuracy for determining surveillance intervals,” the investigators wrote, noting that this finding highlights the “complexities of human interaction with AI modules where human intervention could lead to worse outcomes.”
Further analysis revealed that the sensitivity of autonomous AI for identifying adenomas was 84.8%, slightly higher than the 83.6% sensitivity of the AI-H group. Specificity was 64.4% for autonomous AI vs 63.8% for AI-H. While PPV was higher in the autonomous AI group (85.6%), compared with the AI-H group (78.6%), NPV was lower for autonomous AI than AI-H (63.0% vs 71.0%).
Dr. Djinbachian and colleagues suggested that future research should focus on larger, multicenter trials to validate these findings and further explore the integration of autonomous AI systems in clinical practice. They also noted that improving AI algorithms to accurately diagnose sessile serrated lesions could enhance the overall effectiveness of AI-based optical diagnosis.
“The performance of autonomous AI in accurately diagnosing diminutive polyps and determining appropriate surveillance intervals suggests that it could play a crucial role in streamlining colorectal cancer screening processes, reducing the burden on pathologists, and potentially lowering healthcare costs,” the investigators concluded.The study was supported by Fujifilm, which had no role in the study design or data analysis. Dr. von Renteln reported additional research funding from Vantage and Fujifilm.
In the era of computer vision for endoscopy and colonoscopy, current paradigms rely on AI as a co-pilot or second observer, with the physician serving as the final arbiter in procedure-related decision-making. This study by Djinbachian and Haumesser et al brings up the interesting wrinkle of autonomous AI as a potentially superior (or noninferior) option in narrow, task-specific use cases.
In this study, human input from the endoscopist after CADx diagnosis led to lower agreement between the AI-predicted diagnosis and corresponding surveillance intervals; human oversight more often incorrectly changed the resultant diagnosis and led to shorter than recommended surveillance intervals.
This study offers a small but very important update to the growing body of literature on CADx in colonoscopy. So far, prospective validation of CADx compared with the human eye for in-situ diagnosis of polyps has provided mixed results. This study is one of the first to examine the potential role of “automatic” CADx without additional human input and sheds light on the importance of the AI-human hybrid in medical care. How do the ways in which humans interact with the user interface and output of AI lead to changes in outcome? How can we optimize the AI-human interaction in order to provide optimal results?
Jeremy R. Glissen Brown is an assistant professor in the Department of Internal Medicine and Division of Gastroenterology at Duke University Medical Center, Durham, North Carolina. He has served as a consultant for Medtronic and Olympus, and on the advisory board for Odin Vision.
In the era of computer vision for endoscopy and colonoscopy, current paradigms rely on AI as a co-pilot or second observer, with the physician serving as the final arbiter in procedure-related decision-making. This study by Djinbachian and Haumesser et al brings up the interesting wrinkle of autonomous AI as a potentially superior (or noninferior) option in narrow, task-specific use cases.
In this study, human input from the endoscopist after CADx diagnosis led to lower agreement between the AI-predicted diagnosis and corresponding surveillance intervals; human oversight more often incorrectly changed the resultant diagnosis and led to shorter than recommended surveillance intervals.
This study offers a small but very important update to the growing body of literature on CADx in colonoscopy. So far, prospective validation of CADx compared with the human eye for in-situ diagnosis of polyps has provided mixed results. This study is one of the first to examine the potential role of “automatic” CADx without additional human input and sheds light on the importance of the AI-human hybrid in medical care. How do the ways in which humans interact with the user interface and output of AI lead to changes in outcome? How can we optimize the AI-human interaction in order to provide optimal results?
Jeremy R. Glissen Brown is an assistant professor in the Department of Internal Medicine and Division of Gastroenterology at Duke University Medical Center, Durham, North Carolina. He has served as a consultant for Medtronic and Olympus, and on the advisory board for Odin Vision.
In the era of computer vision for endoscopy and colonoscopy, current paradigms rely on AI as a co-pilot or second observer, with the physician serving as the final arbiter in procedure-related decision-making. This study by Djinbachian and Haumesser et al brings up the interesting wrinkle of autonomous AI as a potentially superior (or noninferior) option in narrow, task-specific use cases.
In this study, human input from the endoscopist after CADx diagnosis led to lower agreement between the AI-predicted diagnosis and corresponding surveillance intervals; human oversight more often incorrectly changed the resultant diagnosis and led to shorter than recommended surveillance intervals.
This study offers a small but very important update to the growing body of literature on CADx in colonoscopy. So far, prospective validation of CADx compared with the human eye for in-situ diagnosis of polyps has provided mixed results. This study is one of the first to examine the potential role of “automatic” CADx without additional human input and sheds light on the importance of the AI-human hybrid in medical care. How do the ways in which humans interact with the user interface and output of AI lead to changes in outcome? How can we optimize the AI-human interaction in order to provide optimal results?
Jeremy R. Glissen Brown is an assistant professor in the Department of Internal Medicine and Division of Gastroenterology at Duke University Medical Center, Durham, North Carolina. He has served as a consultant for Medtronic and Olympus, and on the advisory board for Odin Vision.
, while providing greater alignment with pathology-based surveillance intervals, based on a randomized controlled trial.
These findings suggest that autonomous AI may one day replace histologic assessment of diminutive polyps, reported lead author Roupen Djinbachian, MD, of the Montreal University Hospital Research Center, Montreal, Quebec, Canada, and colleagues.Optical diagnosis of diminutive colorectal polyps has been proposed as a cost-effective alternative to histologic diagnosis, but its implementation in general clinical practice has been hindered by endoscopists’ concerns about incorrect diagnoses, the investigators wrote in Gastroenterology.“AI-based systems (CADx) have been proposed as a solution to these barriers to implementation, with studies showing high adherence to Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds when using AI-H,” they wrote. “However, the efficacy and safety of autonomous AI-based diagnostic platforms have not yet been evaluated.”
To address this knowledge gap, Dr. Djinbachian and colleagues conducted a randomized controlled noninferiority trial involving 467 patients, all of whom underwent elective colonoscopies at a single academic institution.
Participants were randomly assigned to one of two groups. The first group received an optical diagnosis of diminutive (1-5 mm) colorectal polyps using an autonomous AI-based CADx system without any human input. The second group had diagnoses performed by endoscopists who used AI-H to make their optical diagnoses.
The primary outcome was the accuracy of optical diagnosis compared with the gold standard of histologic evaluation. Secondarily, the investigators explored associations between pathology-based surveillance intervals and various measures of accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
The results showed that the accuracy of optical diagnosis for diminutive polyps was similar between the two groups, supporting noninferiority. Autonomous AI achieved an accuracy rate of 77.2%, while the AI-H group had an accuracy of 72.1%, which was not statistically significant (P = .86).
But when it came to pathology-based surveillance intervals, autonomous AI showed a clear advantage; the autonomous AI system achieved a 91.5% agreement rate, compared with 82.1% for the AI-H group (P = .016).
“These findings indicate that autonomous AI not only matches but also surpasses AI-H in accuracy for determining surveillance intervals,” the investigators wrote, noting that this finding highlights the “complexities of human interaction with AI modules where human intervention could lead to worse outcomes.”
Further analysis revealed that the sensitivity of autonomous AI for identifying adenomas was 84.8%, slightly higher than the 83.6% sensitivity of the AI-H group. Specificity was 64.4% for autonomous AI vs 63.8% for AI-H. While PPV was higher in the autonomous AI group (85.6%), compared with the AI-H group (78.6%), NPV was lower for autonomous AI than AI-H (63.0% vs 71.0%).
Dr. Djinbachian and colleagues suggested that future research should focus on larger, multicenter trials to validate these findings and further explore the integration of autonomous AI systems in clinical practice. They also noted that improving AI algorithms to accurately diagnose sessile serrated lesions could enhance the overall effectiveness of AI-based optical diagnosis.
“The performance of autonomous AI in accurately diagnosing diminutive polyps and determining appropriate surveillance intervals suggests that it could play a crucial role in streamlining colorectal cancer screening processes, reducing the burden on pathologists, and potentially lowering healthcare costs,” the investigators concluded.The study was supported by Fujifilm, which had no role in the study design or data analysis. Dr. von Renteln reported additional research funding from Vantage and Fujifilm.
, while providing greater alignment with pathology-based surveillance intervals, based on a randomized controlled trial.
These findings suggest that autonomous AI may one day replace histologic assessment of diminutive polyps, reported lead author Roupen Djinbachian, MD, of the Montreal University Hospital Research Center, Montreal, Quebec, Canada, and colleagues.Optical diagnosis of diminutive colorectal polyps has been proposed as a cost-effective alternative to histologic diagnosis, but its implementation in general clinical practice has been hindered by endoscopists’ concerns about incorrect diagnoses, the investigators wrote in Gastroenterology.“AI-based systems (CADx) have been proposed as a solution to these barriers to implementation, with studies showing high adherence to Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) thresholds when using AI-H,” they wrote. “However, the efficacy and safety of autonomous AI-based diagnostic platforms have not yet been evaluated.”
To address this knowledge gap, Dr. Djinbachian and colleagues conducted a randomized controlled noninferiority trial involving 467 patients, all of whom underwent elective colonoscopies at a single academic institution.
Participants were randomly assigned to one of two groups. The first group received an optical diagnosis of diminutive (1-5 mm) colorectal polyps using an autonomous AI-based CADx system without any human input. The second group had diagnoses performed by endoscopists who used AI-H to make their optical diagnoses.
The primary outcome was the accuracy of optical diagnosis compared with the gold standard of histologic evaluation. Secondarily, the investigators explored associations between pathology-based surveillance intervals and various measures of accuracy, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
The results showed that the accuracy of optical diagnosis for diminutive polyps was similar between the two groups, supporting noninferiority. Autonomous AI achieved an accuracy rate of 77.2%, while the AI-H group had an accuracy of 72.1%, which was not statistically significant (P = .86).
But when it came to pathology-based surveillance intervals, autonomous AI showed a clear advantage; the autonomous AI system achieved a 91.5% agreement rate, compared with 82.1% for the AI-H group (P = .016).
“These findings indicate that autonomous AI not only matches but also surpasses AI-H in accuracy for determining surveillance intervals,” the investigators wrote, noting that this finding highlights the “complexities of human interaction with AI modules where human intervention could lead to worse outcomes.”
Further analysis revealed that the sensitivity of autonomous AI for identifying adenomas was 84.8%, slightly higher than the 83.6% sensitivity of the AI-H group. Specificity was 64.4% for autonomous AI vs 63.8% for AI-H. While PPV was higher in the autonomous AI group (85.6%), compared with the AI-H group (78.6%), NPV was lower for autonomous AI than AI-H (63.0% vs 71.0%).
Dr. Djinbachian and colleagues suggested that future research should focus on larger, multicenter trials to validate these findings and further explore the integration of autonomous AI systems in clinical practice. They also noted that improving AI algorithms to accurately diagnose sessile serrated lesions could enhance the overall effectiveness of AI-based optical diagnosis.
“The performance of autonomous AI in accurately diagnosing diminutive polyps and determining appropriate surveillance intervals suggests that it could play a crucial role in streamlining colorectal cancer screening processes, reducing the burden on pathologists, and potentially lowering healthcare costs,” the investigators concluded.The study was supported by Fujifilm, which had no role in the study design or data analysis. Dr. von Renteln reported additional research funding from Vantage and Fujifilm.
FROM GASTROENTEROLOGY
Gastroenterology Data Trends 2024
In this issue:
- Eosinophilic Gastrointestinal Diseases: Beyond EoE
Nirmala Gonsalves, MD, AGAF, FACG - The Changing Face of IBD: Beyond the Western World
Gilaad G. Kaplan, MD, MPH, AGAF; Paulo Kotze, MD, MS, PhD; Siew C. Ng, MBBS, PhD, AGAF - Role of Non-invasive Biomarkers in the Evaluation and Management of MASLD
Julia J. Wattacheril, MD, MPH - The Emerging Role of Liquid Biopsy in the Diagnosis and Management of CRC
David Lieberman, MD, AGAF - Cannabinoids and Digestive Disorders
Jami A. Kinnucan, MD, AGAF, FACG - AI and Machine Learning in IBD: Promising Applications and Remaining Challenges
Shirley Cohen-Mekelburg, MD, MS - Simulation-Based Training in Endoscopy: Benefits and Challenges
Richa Shukla, MD - Fluid Management in Acute Pancreatitis
Jorge D. Machicado, MD, MPH
In this issue:
- Eosinophilic Gastrointestinal Diseases: Beyond EoE
Nirmala Gonsalves, MD, AGAF, FACG - The Changing Face of IBD: Beyond the Western World
Gilaad G. Kaplan, MD, MPH, AGAF; Paulo Kotze, MD, MS, PhD; Siew C. Ng, MBBS, PhD, AGAF - Role of Non-invasive Biomarkers in the Evaluation and Management of MASLD
Julia J. Wattacheril, MD, MPH - The Emerging Role of Liquid Biopsy in the Diagnosis and Management of CRC
David Lieberman, MD, AGAF - Cannabinoids and Digestive Disorders
Jami A. Kinnucan, MD, AGAF, FACG - AI and Machine Learning in IBD: Promising Applications and Remaining Challenges
Shirley Cohen-Mekelburg, MD, MS - Simulation-Based Training in Endoscopy: Benefits and Challenges
Richa Shukla, MD - Fluid Management in Acute Pancreatitis
Jorge D. Machicado, MD, MPH
In this issue:
- Eosinophilic Gastrointestinal Diseases: Beyond EoE
Nirmala Gonsalves, MD, AGAF, FACG - The Changing Face of IBD: Beyond the Western World
Gilaad G. Kaplan, MD, MPH, AGAF; Paulo Kotze, MD, MS, PhD; Siew C. Ng, MBBS, PhD, AGAF - Role of Non-invasive Biomarkers in the Evaluation and Management of MASLD
Julia J. Wattacheril, MD, MPH - The Emerging Role of Liquid Biopsy in the Diagnosis and Management of CRC
David Lieberman, MD, AGAF - Cannabinoids and Digestive Disorders
Jami A. Kinnucan, MD, AGAF, FACG - AI and Machine Learning in IBD: Promising Applications and Remaining Challenges
Shirley Cohen-Mekelburg, MD, MS - Simulation-Based Training in Endoscopy: Benefits and Challenges
Richa Shukla, MD - Fluid Management in Acute Pancreatitis
Jorge D. Machicado, MD, MPH