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The Long, Controversial Search for a ‘Cancer Microbiome’
Last year, the controversy heightened when experts questioned a high-profile study — a 2020 analysis claiming that the tumors of 33 different cancers had their own unique microbiomes — on whether the “signature” of these bacterial compositions could help diagnose cancer.
The incident renewed the spotlight on “tumor microbiomes” because of the bold claims of the original paper and the strongly worded refutations of those claims. The broader field has focused primarily on ways the body’s microbiome interacts with cancers and cancer treatment.
This controversy has highlighted the challenges of making headway in a field where researchers may not even have the tools yet to puzzle-out the wide-ranging implications the microbiome holds for cancer diagnosis and treatment.
But it is also part of a provocative question within that larger field: whether tumors in the body, far from the natural microbiome in the gut, have their own thriving communities of bacteria, viruses, and fungi. And, if they do, how do those tumor microbiomes affect the development and progression of the cancer and the effectiveness of cancer therapies?
Cancer Controversy
The evidence is undeniable that some microbes can directly cause certain cancers and that the human gut microbiome can influence the effectiveness of certain therapies. Beyond that established science, however, the research has raised as many questions as answers about what we do and don’t know about microbiota and cancer.
The only confirmed microbiomes are on the skin and in the gut, mouth, and vagina, which are all areas with an easy direct route for bacteria to enter and grow in or on the body. A series of papers in recent years have suggested that other internal organs, and tumors within them, may have their own microbiomes.
“Whether microbes exist in tumors of internal organs beyond body surfaces exposed to the environment is a different matter,” said Ivan Vujkovic-Cvijin, PhD, an assistant professor of biomedical sciences and gastroenterology at Cedars-Sinai Medical Center in Los Angeles, whose lab studies how human gut microbes affect inflammatory diseases. “We’ve only recently had the tools to study that question on a molecular level, and the reported results have been conflicting.”
For example, research allegedly identified microbiota in the human placenta nearly one decade ago. But subsequent research contradicted those claims and showed that the source of the “placental microbiome” was actually contamination. Subsequent similar studies for other parts of the body faced the same scrutiny and, often, eventual debunking.
“Most likely, our immune system has undergone selective pressure to eliminate everything that crosses the gut barrier because there’s not much benefit to the body to have bacteria run amok in our internal organs,” Dr. Vujkovic-Cvijin said. “That can only disrupt the functioning of our tissues, to have an external organism living inside them.”
The controversy that erupted last summer, surrounding research from the lab of Rob Knight, PhD, at the University of California, San Diego, centered on a slightly different but related question: Could tumors harbor their own microbiomes?
This news organization spoke with two of the authors who published a paper contesting Dr. Knight’s findings: Steven Salzberg, PhD, a professor of biomedical engineering at John Hopkins Medicine, Baltimore, Maryland, and Abraham Gihawi, PhD, a research fellow at Norwich Medical School at the University of East Anglia in the United Kingdom.
Dr. Salzberg described two major problems with Dr. Knight’s study.
“What they found were false positives because of contamination in the database and flaws in their methods,” Dr. Salzberg said. “I can’t prove there’s no cancer microbiome, but I can say the cancer microbiomes that they reported don’t exist because the species they were finding aren’t there.”
Dr. Knight disagrees with Dr. Salzberg’s findings, noting that Dr. Salzberg and his co-authors did not examine the publicly available databases used in his study. In a written response, he said that his team’s examination of the database revealed that less than 1% of the microbial genomes overlapped with human ones and that removing them did not change their findings.
Dr. Knight also noted that his team could still “distinguish cancer types by their microbiome” even after running their analysis without the technique that Dr. Salzberg found fault with.
Dr. Salzberg said that the database linked above is not the one Dr. Knight’s study used, however. “The primary database in their study was never made public (it’s too large, they said), and it has/had about 69,000 genomes,” Dr. Salzberg said by email. “But even if we did, this is irrelevant. He’s trying to distract from the primary errors in their study,” which Dr. Salzberg said Dr. Knight’s team has not addressed.
The critiques Dr. Salzberg raised have been leveled at other studies investigating microbiomes specifically within tumors and independent of the body’s microbiome.
For example, a 2019 study in Nature described a fungal microbiome in pancreatic cancer that a Nature paper 4 years later directly contradicted, citing flaws that invalidated the original findings. A different 2019 study in Cell examined pancreatic tumor microbiota and patient outcomes, but it’s unclear whether the microorganisms moved from the gut to the pancreas or “constitute a durably colonized community that lives inside the tumor,” which remains a matter of debate, Dr. Vujkovic-Cvijin said.
A 2020 study in Science suggested diverse microbial communities in seven tumor types, but those findings were similarly called into question. That study stated that “bacteria were first detected in human tumors more than 100 years ago” and that “bacteria are well-known residents in human tumors,” but Dr. Salzberg considers those statements misleading.
It’s true that bacteria and viruses have been detected in tumors because “there’s very good evidence that an acute infection caused by a very small number of viruses and bacteria can cause a tumor,” Dr. Salzberg said. Human papillomavirus, for example, can cause six different types of cancer. Inflammation and ulcers caused by Helicobacter pylori may progress to stomach cancer, and Fusobacterium nucleatum and Enterococcus faecalis have been shown to contribute to colorectal cancer. Those examples differ from a microbiome; this “a community of bacteria and possibly other microscopic bugs, like fungi, that are happily living in the tumor” the same way microbes reside in our guts, he said.
Dr. Knight said that many bacteria his team identified “have been confirmed independently in subsequent work.” He acknowledged, however, that more research is needed.
Several of the contested studies above were among a lengthy list that Dr. Knight provided, noting that most of the disagreements “have two sides to them, and critiques from one particular group does not immediately invalidate a reported finding.”
Yet, many of the papers Dr. Knight listed are precisely the types that skeptics like Dr. Salzberg believe are too flawed to draw reliable conclusions.
“I think many agree that microbes may exist within tumors that are exposed to the environment, like tumors of the skin, gut, and mouth,” Dr. Vujkovic-Cvijin said. It’s less clear, however, whether tumors further from the body’s microbiome harbor any microbes or where they came from if they do. Microbial signals in organs elsewhere in the body become faint quickly, he said.
Underdeveloped Technology
Though Dr. Salzberg said that the concept of a tumor microbiome is “implausible” because there’s no easy route for bacteria to reach internal organs, it’s unclear whether scientists have the technology yet to adequately answer this question.
For one thing, samples in these types of studies are typically “ultra-low biomass samples, where the signal — the amount of microbes in the sample — is so low that it’s comparable to how much would be expected to be found in reagents and environmental contamination through processing,” Dr. Vujkovic-Cvijin explained. Many polymerases used to amplify a DNA signal, for example, are made in bacteria and may retain trace amounts identified in these studies.
Dr. Knight agreed that low biomass is a challenge in this field but is not an unsurmountable one.
Another challenge is that study samples, as with Dr. Knight’s work, were collected during routine surgeries without the intent to find a microbial signal. Simply using a scalpel to cut through the skin means cutting through a layer of bacteria, and surgery rooms are not designed to eliminate all bacteria. Some work has even shown there is a “hospital microbiome,” so “you can easily have that creep into your signal and mistake it for tumor-resident bacteria,” Dr. Vujkovic-Cvijin said.
Dr. Knight asserted that the samples are taken under sterile conditions, but other researchers do not think the level of sterility necessary for completely clean samples is possible.
“Just because it’s in your sample doesn’t mean it was in your tumor,” Dr. Gihawi said.
Even if scientists can retrieve a reliable sample without contamination, analyzing it requires comparing the genetic material to existing databases of microbial genomes. Yet, contamination and misclassification of genetic sequences can be problems in those reference genomes too, Dr. Gihawi explained.
Machine learning algorithms have a role in interpreting data, but “we need to be careful of what we use them for,” he added.
“These techniques are in their infancy, and we’re starting to chase them down, which is why we need to move microbiome research in a way that can be used clinically,” Dr. Gihawi said.
Influence on Cancer Treatment Outcomes
Again, however, the question of whether microbiomes exist within tumors is only one slice of the much larger field looking at microbiomes and cancer, including its influence on cancer treatment outcomes. Although much remains to be learned, less controversy exists over the thousands of studies in the past two decades that have gradually revealed how the body’s microbiome can affect both the course of a cancer and the effectiveness of different treatments.
The growing research showing the importance of the gut microbiome in cancer treatments is not surprising given its role in immunity more broadly. Because the human immune system must recognize and defend against microbes, the microbiome helps train it, Dr. Vujkovic-Cvijin said.
Some bacteria can escape the gut — a phenomenon called bacterial translocation — and may aid in fighting tumors. To grow large enough to be seen on imaging, tumors need to evolve several abilities, such as growing enough vascularization to receive blood flow and shutting down local immune responses.
“Any added boost, like immunotherapy, has a chance of breaking through that immune forcefield and killing the tumor cells,” Dr. Vujkovic-Cvijin said. Escaped gut bacteria may provide that boost.
“There’s a lot of evidence that depletion of the gut microbiome impairs immunotherapy and chemotherapy. The thinking behind some of those studies is that gut microbes can cross the gut barrier and when they do, they activate the immune system,” he said.
In mice engineered to have sterile guts, for example, the lack of bacteria results in less effective immune systems, Dr. Vujkovic-Cvijin pointed out. A host of research has shown that antibiotic exposure during and even 6 months before immunotherapy dramatically reduces survival rates. “That’s pretty convincing to me that gut microbes are important,” he said.
Dr. Vujkovic-Cvijin cautioned that there continues to be controversy on understanding which bacteria are important for response to immunotherapy. “The field is still in its infancy in terms of understanding which bacteria are most important for these effects,” he said.
Dr. Knight suggested that escaped bacteria may be the genesis of the ones that he and other researchers believe exist in tumors. “Because tumor microbes must come from somewhere, it is to be expected that some of those microbes will be co-opted from body-site specific commensals.”
It’s also possible that metabolites released from gut bacteria escape the gut and could theoretically affect distant tumor growth, Dr. Gihawi said. The most promising avenue of research in this area is metabolites being used as biomarkers, added Dr. Gihawi, whose lab published research on a link between bacteria detected in men’s urine and a more aggressive subset of prostate cancers. But that research is not far enough along to develop lab tests for clinical use, he noted.
No Consensus Yet
Even before the controversy erupted around Dr. Knight’s research, he co-founded the company Micronoma to develop cancer tests based on his microbe findings. The company has raised $17.5 million from private investors as of August 2023 and received the US Food and Drug Administration’s Breakthrough Device designation, allowing the firm to fast-track clinical trials testing the technology. The recent critiques have not changed the company’s plans.
It’s safe to say that scientists will continue to research and debate the possibility of tumor microbiomes until a consensus emerges.
“The field is evolving and studies testing the reproducibility of tumor-resident microbial signals are essential for developing our understanding in this area,” Dr. Vujkovic-Cvijin said.
Even if that path ultimately leads nowhere, as Dr. Salzberg expects, research into microbiomes and cancer has plenty of other directions to go.
“I’m actually quite an optimist,” Dr. Gihawi said. “I think there’s a lot of scope for some really good research here, especially in the sites where we know there is a strong microbiome, such as the gastrointestinal tract.”
A version of this article appeared on Medscape.com.
Last year, the controversy heightened when experts questioned a high-profile study — a 2020 analysis claiming that the tumors of 33 different cancers had their own unique microbiomes — on whether the “signature” of these bacterial compositions could help diagnose cancer.
The incident renewed the spotlight on “tumor microbiomes” because of the bold claims of the original paper and the strongly worded refutations of those claims. The broader field has focused primarily on ways the body’s microbiome interacts with cancers and cancer treatment.
This controversy has highlighted the challenges of making headway in a field where researchers may not even have the tools yet to puzzle-out the wide-ranging implications the microbiome holds for cancer diagnosis and treatment.
But it is also part of a provocative question within that larger field: whether tumors in the body, far from the natural microbiome in the gut, have their own thriving communities of bacteria, viruses, and fungi. And, if they do, how do those tumor microbiomes affect the development and progression of the cancer and the effectiveness of cancer therapies?
Cancer Controversy
The evidence is undeniable that some microbes can directly cause certain cancers and that the human gut microbiome can influence the effectiveness of certain therapies. Beyond that established science, however, the research has raised as many questions as answers about what we do and don’t know about microbiota and cancer.
The only confirmed microbiomes are on the skin and in the gut, mouth, and vagina, which are all areas with an easy direct route for bacteria to enter and grow in or on the body. A series of papers in recent years have suggested that other internal organs, and tumors within them, may have their own microbiomes.
“Whether microbes exist in tumors of internal organs beyond body surfaces exposed to the environment is a different matter,” said Ivan Vujkovic-Cvijin, PhD, an assistant professor of biomedical sciences and gastroenterology at Cedars-Sinai Medical Center in Los Angeles, whose lab studies how human gut microbes affect inflammatory diseases. “We’ve only recently had the tools to study that question on a molecular level, and the reported results have been conflicting.”
For example, research allegedly identified microbiota in the human placenta nearly one decade ago. But subsequent research contradicted those claims and showed that the source of the “placental microbiome” was actually contamination. Subsequent similar studies for other parts of the body faced the same scrutiny and, often, eventual debunking.
“Most likely, our immune system has undergone selective pressure to eliminate everything that crosses the gut barrier because there’s not much benefit to the body to have bacteria run amok in our internal organs,” Dr. Vujkovic-Cvijin said. “That can only disrupt the functioning of our tissues, to have an external organism living inside them.”
The controversy that erupted last summer, surrounding research from the lab of Rob Knight, PhD, at the University of California, San Diego, centered on a slightly different but related question: Could tumors harbor their own microbiomes?
This news organization spoke with two of the authors who published a paper contesting Dr. Knight’s findings: Steven Salzberg, PhD, a professor of biomedical engineering at John Hopkins Medicine, Baltimore, Maryland, and Abraham Gihawi, PhD, a research fellow at Norwich Medical School at the University of East Anglia in the United Kingdom.
Dr. Salzberg described two major problems with Dr. Knight’s study.
“What they found were false positives because of contamination in the database and flaws in their methods,” Dr. Salzberg said. “I can’t prove there’s no cancer microbiome, but I can say the cancer microbiomes that they reported don’t exist because the species they were finding aren’t there.”
Dr. Knight disagrees with Dr. Salzberg’s findings, noting that Dr. Salzberg and his co-authors did not examine the publicly available databases used in his study. In a written response, he said that his team’s examination of the database revealed that less than 1% of the microbial genomes overlapped with human ones and that removing them did not change their findings.
Dr. Knight also noted that his team could still “distinguish cancer types by their microbiome” even after running their analysis without the technique that Dr. Salzberg found fault with.
Dr. Salzberg said that the database linked above is not the one Dr. Knight’s study used, however. “The primary database in their study was never made public (it’s too large, they said), and it has/had about 69,000 genomes,” Dr. Salzberg said by email. “But even if we did, this is irrelevant. He’s trying to distract from the primary errors in their study,” which Dr. Salzberg said Dr. Knight’s team has not addressed.
The critiques Dr. Salzberg raised have been leveled at other studies investigating microbiomes specifically within tumors and independent of the body’s microbiome.
For example, a 2019 study in Nature described a fungal microbiome in pancreatic cancer that a Nature paper 4 years later directly contradicted, citing flaws that invalidated the original findings. A different 2019 study in Cell examined pancreatic tumor microbiota and patient outcomes, but it’s unclear whether the microorganisms moved from the gut to the pancreas or “constitute a durably colonized community that lives inside the tumor,” which remains a matter of debate, Dr. Vujkovic-Cvijin said.
A 2020 study in Science suggested diverse microbial communities in seven tumor types, but those findings were similarly called into question. That study stated that “bacteria were first detected in human tumors more than 100 years ago” and that “bacteria are well-known residents in human tumors,” but Dr. Salzberg considers those statements misleading.
It’s true that bacteria and viruses have been detected in tumors because “there’s very good evidence that an acute infection caused by a very small number of viruses and bacteria can cause a tumor,” Dr. Salzberg said. Human papillomavirus, for example, can cause six different types of cancer. Inflammation and ulcers caused by Helicobacter pylori may progress to stomach cancer, and Fusobacterium nucleatum and Enterococcus faecalis have been shown to contribute to colorectal cancer. Those examples differ from a microbiome; this “a community of bacteria and possibly other microscopic bugs, like fungi, that are happily living in the tumor” the same way microbes reside in our guts, he said.
Dr. Knight said that many bacteria his team identified “have been confirmed independently in subsequent work.” He acknowledged, however, that more research is needed.
Several of the contested studies above were among a lengthy list that Dr. Knight provided, noting that most of the disagreements “have two sides to them, and critiques from one particular group does not immediately invalidate a reported finding.”
Yet, many of the papers Dr. Knight listed are precisely the types that skeptics like Dr. Salzberg believe are too flawed to draw reliable conclusions.
“I think many agree that microbes may exist within tumors that are exposed to the environment, like tumors of the skin, gut, and mouth,” Dr. Vujkovic-Cvijin said. It’s less clear, however, whether tumors further from the body’s microbiome harbor any microbes or where they came from if they do. Microbial signals in organs elsewhere in the body become faint quickly, he said.
Underdeveloped Technology
Though Dr. Salzberg said that the concept of a tumor microbiome is “implausible” because there’s no easy route for bacteria to reach internal organs, it’s unclear whether scientists have the technology yet to adequately answer this question.
For one thing, samples in these types of studies are typically “ultra-low biomass samples, where the signal — the amount of microbes in the sample — is so low that it’s comparable to how much would be expected to be found in reagents and environmental contamination through processing,” Dr. Vujkovic-Cvijin explained. Many polymerases used to amplify a DNA signal, for example, are made in bacteria and may retain trace amounts identified in these studies.
Dr. Knight agreed that low biomass is a challenge in this field but is not an unsurmountable one.
Another challenge is that study samples, as with Dr. Knight’s work, were collected during routine surgeries without the intent to find a microbial signal. Simply using a scalpel to cut through the skin means cutting through a layer of bacteria, and surgery rooms are not designed to eliminate all bacteria. Some work has even shown there is a “hospital microbiome,” so “you can easily have that creep into your signal and mistake it for tumor-resident bacteria,” Dr. Vujkovic-Cvijin said.
Dr. Knight asserted that the samples are taken under sterile conditions, but other researchers do not think the level of sterility necessary for completely clean samples is possible.
“Just because it’s in your sample doesn’t mean it was in your tumor,” Dr. Gihawi said.
Even if scientists can retrieve a reliable sample without contamination, analyzing it requires comparing the genetic material to existing databases of microbial genomes. Yet, contamination and misclassification of genetic sequences can be problems in those reference genomes too, Dr. Gihawi explained.
Machine learning algorithms have a role in interpreting data, but “we need to be careful of what we use them for,” he added.
“These techniques are in their infancy, and we’re starting to chase them down, which is why we need to move microbiome research in a way that can be used clinically,” Dr. Gihawi said.
Influence on Cancer Treatment Outcomes
Again, however, the question of whether microbiomes exist within tumors is only one slice of the much larger field looking at microbiomes and cancer, including its influence on cancer treatment outcomes. Although much remains to be learned, less controversy exists over the thousands of studies in the past two decades that have gradually revealed how the body’s microbiome can affect both the course of a cancer and the effectiveness of different treatments.
The growing research showing the importance of the gut microbiome in cancer treatments is not surprising given its role in immunity more broadly. Because the human immune system must recognize and defend against microbes, the microbiome helps train it, Dr. Vujkovic-Cvijin said.
Some bacteria can escape the gut — a phenomenon called bacterial translocation — and may aid in fighting tumors. To grow large enough to be seen on imaging, tumors need to evolve several abilities, such as growing enough vascularization to receive blood flow and shutting down local immune responses.
“Any added boost, like immunotherapy, has a chance of breaking through that immune forcefield and killing the tumor cells,” Dr. Vujkovic-Cvijin said. Escaped gut bacteria may provide that boost.
“There’s a lot of evidence that depletion of the gut microbiome impairs immunotherapy and chemotherapy. The thinking behind some of those studies is that gut microbes can cross the gut barrier and when they do, they activate the immune system,” he said.
In mice engineered to have sterile guts, for example, the lack of bacteria results in less effective immune systems, Dr. Vujkovic-Cvijin pointed out. A host of research has shown that antibiotic exposure during and even 6 months before immunotherapy dramatically reduces survival rates. “That’s pretty convincing to me that gut microbes are important,” he said.
Dr. Vujkovic-Cvijin cautioned that there continues to be controversy on understanding which bacteria are important for response to immunotherapy. “The field is still in its infancy in terms of understanding which bacteria are most important for these effects,” he said.
Dr. Knight suggested that escaped bacteria may be the genesis of the ones that he and other researchers believe exist in tumors. “Because tumor microbes must come from somewhere, it is to be expected that some of those microbes will be co-opted from body-site specific commensals.”
It’s also possible that metabolites released from gut bacteria escape the gut and could theoretically affect distant tumor growth, Dr. Gihawi said. The most promising avenue of research in this area is metabolites being used as biomarkers, added Dr. Gihawi, whose lab published research on a link between bacteria detected in men’s urine and a more aggressive subset of prostate cancers. But that research is not far enough along to develop lab tests for clinical use, he noted.
No Consensus Yet
Even before the controversy erupted around Dr. Knight’s research, he co-founded the company Micronoma to develop cancer tests based on his microbe findings. The company has raised $17.5 million from private investors as of August 2023 and received the US Food and Drug Administration’s Breakthrough Device designation, allowing the firm to fast-track clinical trials testing the technology. The recent critiques have not changed the company’s plans.
It’s safe to say that scientists will continue to research and debate the possibility of tumor microbiomes until a consensus emerges.
“The field is evolving and studies testing the reproducibility of tumor-resident microbial signals are essential for developing our understanding in this area,” Dr. Vujkovic-Cvijin said.
Even if that path ultimately leads nowhere, as Dr. Salzberg expects, research into microbiomes and cancer has plenty of other directions to go.
“I’m actually quite an optimist,” Dr. Gihawi said. “I think there’s a lot of scope for some really good research here, especially in the sites where we know there is a strong microbiome, such as the gastrointestinal tract.”
A version of this article appeared on Medscape.com.
Last year, the controversy heightened when experts questioned a high-profile study — a 2020 analysis claiming that the tumors of 33 different cancers had their own unique microbiomes — on whether the “signature” of these bacterial compositions could help diagnose cancer.
The incident renewed the spotlight on “tumor microbiomes” because of the bold claims of the original paper and the strongly worded refutations of those claims. The broader field has focused primarily on ways the body’s microbiome interacts with cancers and cancer treatment.
This controversy has highlighted the challenges of making headway in a field where researchers may not even have the tools yet to puzzle-out the wide-ranging implications the microbiome holds for cancer diagnosis and treatment.
But it is also part of a provocative question within that larger field: whether tumors in the body, far from the natural microbiome in the gut, have their own thriving communities of bacteria, viruses, and fungi. And, if they do, how do those tumor microbiomes affect the development and progression of the cancer and the effectiveness of cancer therapies?
Cancer Controversy
The evidence is undeniable that some microbes can directly cause certain cancers and that the human gut microbiome can influence the effectiveness of certain therapies. Beyond that established science, however, the research has raised as many questions as answers about what we do and don’t know about microbiota and cancer.
The only confirmed microbiomes are on the skin and in the gut, mouth, and vagina, which are all areas with an easy direct route for bacteria to enter and grow in or on the body. A series of papers in recent years have suggested that other internal organs, and tumors within them, may have their own microbiomes.
“Whether microbes exist in tumors of internal organs beyond body surfaces exposed to the environment is a different matter,” said Ivan Vujkovic-Cvijin, PhD, an assistant professor of biomedical sciences and gastroenterology at Cedars-Sinai Medical Center in Los Angeles, whose lab studies how human gut microbes affect inflammatory diseases. “We’ve only recently had the tools to study that question on a molecular level, and the reported results have been conflicting.”
For example, research allegedly identified microbiota in the human placenta nearly one decade ago. But subsequent research contradicted those claims and showed that the source of the “placental microbiome” was actually contamination. Subsequent similar studies for other parts of the body faced the same scrutiny and, often, eventual debunking.
“Most likely, our immune system has undergone selective pressure to eliminate everything that crosses the gut barrier because there’s not much benefit to the body to have bacteria run amok in our internal organs,” Dr. Vujkovic-Cvijin said. “That can only disrupt the functioning of our tissues, to have an external organism living inside them.”
The controversy that erupted last summer, surrounding research from the lab of Rob Knight, PhD, at the University of California, San Diego, centered on a slightly different but related question: Could tumors harbor their own microbiomes?
This news organization spoke with two of the authors who published a paper contesting Dr. Knight’s findings: Steven Salzberg, PhD, a professor of biomedical engineering at John Hopkins Medicine, Baltimore, Maryland, and Abraham Gihawi, PhD, a research fellow at Norwich Medical School at the University of East Anglia in the United Kingdom.
Dr. Salzberg described two major problems with Dr. Knight’s study.
“What they found were false positives because of contamination in the database and flaws in their methods,” Dr. Salzberg said. “I can’t prove there’s no cancer microbiome, but I can say the cancer microbiomes that they reported don’t exist because the species they were finding aren’t there.”
Dr. Knight disagrees with Dr. Salzberg’s findings, noting that Dr. Salzberg and his co-authors did not examine the publicly available databases used in his study. In a written response, he said that his team’s examination of the database revealed that less than 1% of the microbial genomes overlapped with human ones and that removing them did not change their findings.
Dr. Knight also noted that his team could still “distinguish cancer types by their microbiome” even after running their analysis without the technique that Dr. Salzberg found fault with.
Dr. Salzberg said that the database linked above is not the one Dr. Knight’s study used, however. “The primary database in their study was never made public (it’s too large, they said), and it has/had about 69,000 genomes,” Dr. Salzberg said by email. “But even if we did, this is irrelevant. He’s trying to distract from the primary errors in their study,” which Dr. Salzberg said Dr. Knight’s team has not addressed.
The critiques Dr. Salzberg raised have been leveled at other studies investigating microbiomes specifically within tumors and independent of the body’s microbiome.
For example, a 2019 study in Nature described a fungal microbiome in pancreatic cancer that a Nature paper 4 years later directly contradicted, citing flaws that invalidated the original findings. A different 2019 study in Cell examined pancreatic tumor microbiota and patient outcomes, but it’s unclear whether the microorganisms moved from the gut to the pancreas or “constitute a durably colonized community that lives inside the tumor,” which remains a matter of debate, Dr. Vujkovic-Cvijin said.
A 2020 study in Science suggested diverse microbial communities in seven tumor types, but those findings were similarly called into question. That study stated that “bacteria were first detected in human tumors more than 100 years ago” and that “bacteria are well-known residents in human tumors,” but Dr. Salzberg considers those statements misleading.
It’s true that bacteria and viruses have been detected in tumors because “there’s very good evidence that an acute infection caused by a very small number of viruses and bacteria can cause a tumor,” Dr. Salzberg said. Human papillomavirus, for example, can cause six different types of cancer. Inflammation and ulcers caused by Helicobacter pylori may progress to stomach cancer, and Fusobacterium nucleatum and Enterococcus faecalis have been shown to contribute to colorectal cancer. Those examples differ from a microbiome; this “a community of bacteria and possibly other microscopic bugs, like fungi, that are happily living in the tumor” the same way microbes reside in our guts, he said.
Dr. Knight said that many bacteria his team identified “have been confirmed independently in subsequent work.” He acknowledged, however, that more research is needed.
Several of the contested studies above were among a lengthy list that Dr. Knight provided, noting that most of the disagreements “have two sides to them, and critiques from one particular group does not immediately invalidate a reported finding.”
Yet, many of the papers Dr. Knight listed are precisely the types that skeptics like Dr. Salzberg believe are too flawed to draw reliable conclusions.
“I think many agree that microbes may exist within tumors that are exposed to the environment, like tumors of the skin, gut, and mouth,” Dr. Vujkovic-Cvijin said. It’s less clear, however, whether tumors further from the body’s microbiome harbor any microbes or where they came from if they do. Microbial signals in organs elsewhere in the body become faint quickly, he said.
Underdeveloped Technology
Though Dr. Salzberg said that the concept of a tumor microbiome is “implausible” because there’s no easy route for bacteria to reach internal organs, it’s unclear whether scientists have the technology yet to adequately answer this question.
For one thing, samples in these types of studies are typically “ultra-low biomass samples, where the signal — the amount of microbes in the sample — is so low that it’s comparable to how much would be expected to be found in reagents and environmental contamination through processing,” Dr. Vujkovic-Cvijin explained. Many polymerases used to amplify a DNA signal, for example, are made in bacteria and may retain trace amounts identified in these studies.
Dr. Knight agreed that low biomass is a challenge in this field but is not an unsurmountable one.
Another challenge is that study samples, as with Dr. Knight’s work, were collected during routine surgeries without the intent to find a microbial signal. Simply using a scalpel to cut through the skin means cutting through a layer of bacteria, and surgery rooms are not designed to eliminate all bacteria. Some work has even shown there is a “hospital microbiome,” so “you can easily have that creep into your signal and mistake it for tumor-resident bacteria,” Dr. Vujkovic-Cvijin said.
Dr. Knight asserted that the samples are taken under sterile conditions, but other researchers do not think the level of sterility necessary for completely clean samples is possible.
“Just because it’s in your sample doesn’t mean it was in your tumor,” Dr. Gihawi said.
Even if scientists can retrieve a reliable sample without contamination, analyzing it requires comparing the genetic material to existing databases of microbial genomes. Yet, contamination and misclassification of genetic sequences can be problems in those reference genomes too, Dr. Gihawi explained.
Machine learning algorithms have a role in interpreting data, but “we need to be careful of what we use them for,” he added.
“These techniques are in their infancy, and we’re starting to chase them down, which is why we need to move microbiome research in a way that can be used clinically,” Dr. Gihawi said.
Influence on Cancer Treatment Outcomes
Again, however, the question of whether microbiomes exist within tumors is only one slice of the much larger field looking at microbiomes and cancer, including its influence on cancer treatment outcomes. Although much remains to be learned, less controversy exists over the thousands of studies in the past two decades that have gradually revealed how the body’s microbiome can affect both the course of a cancer and the effectiveness of different treatments.
The growing research showing the importance of the gut microbiome in cancer treatments is not surprising given its role in immunity more broadly. Because the human immune system must recognize and defend against microbes, the microbiome helps train it, Dr. Vujkovic-Cvijin said.
Some bacteria can escape the gut — a phenomenon called bacterial translocation — and may aid in fighting tumors. To grow large enough to be seen on imaging, tumors need to evolve several abilities, such as growing enough vascularization to receive blood flow and shutting down local immune responses.
“Any added boost, like immunotherapy, has a chance of breaking through that immune forcefield and killing the tumor cells,” Dr. Vujkovic-Cvijin said. Escaped gut bacteria may provide that boost.
“There’s a lot of evidence that depletion of the gut microbiome impairs immunotherapy and chemotherapy. The thinking behind some of those studies is that gut microbes can cross the gut barrier and when they do, they activate the immune system,” he said.
In mice engineered to have sterile guts, for example, the lack of bacteria results in less effective immune systems, Dr. Vujkovic-Cvijin pointed out. A host of research has shown that antibiotic exposure during and even 6 months before immunotherapy dramatically reduces survival rates. “That’s pretty convincing to me that gut microbes are important,” he said.
Dr. Vujkovic-Cvijin cautioned that there continues to be controversy on understanding which bacteria are important for response to immunotherapy. “The field is still in its infancy in terms of understanding which bacteria are most important for these effects,” he said.
Dr. Knight suggested that escaped bacteria may be the genesis of the ones that he and other researchers believe exist in tumors. “Because tumor microbes must come from somewhere, it is to be expected that some of those microbes will be co-opted from body-site specific commensals.”
It’s also possible that metabolites released from gut bacteria escape the gut and could theoretically affect distant tumor growth, Dr. Gihawi said. The most promising avenue of research in this area is metabolites being used as biomarkers, added Dr. Gihawi, whose lab published research on a link between bacteria detected in men’s urine and a more aggressive subset of prostate cancers. But that research is not far enough along to develop lab tests for clinical use, he noted.
No Consensus Yet
Even before the controversy erupted around Dr. Knight’s research, he co-founded the company Micronoma to develop cancer tests based on his microbe findings. The company has raised $17.5 million from private investors as of August 2023 and received the US Food and Drug Administration’s Breakthrough Device designation, allowing the firm to fast-track clinical trials testing the technology. The recent critiques have not changed the company’s plans.
It’s safe to say that scientists will continue to research and debate the possibility of tumor microbiomes until a consensus emerges.
“The field is evolving and studies testing the reproducibility of tumor-resident microbial signals are essential for developing our understanding in this area,” Dr. Vujkovic-Cvijin said.
Even if that path ultimately leads nowhere, as Dr. Salzberg expects, research into microbiomes and cancer has plenty of other directions to go.
“I’m actually quite an optimist,” Dr. Gihawi said. “I think there’s a lot of scope for some really good research here, especially in the sites where we know there is a strong microbiome, such as the gastrointestinal tract.”
A version of this article appeared on Medscape.com.
Prospect of Better Hours, Less Burnout Fuels Locum Tenens
Insane hours and work-driven burnout are increasingly pernicious forces in medical workplaces. They apparently also are helping steer more physicians toward locum tenens, or temporary, assignments.
In its “2024 Survey of Locum Tenens Physicians and Advanced Practice Professionals,” Coppell, Texas–based staffing firm AMN Healthcare asked doctors, nurse practitioners, and physician assistants why they chose locum tenens work.
The reason chosen most often is improving work hours. Eighty-six percent of respondents said that was the “most important” or a “moderately important” factor. Next was addressing work burnout (80% of respondents), followed by unhappiness with compensation (75%), and dissatisfaction with being a full-time employee (71%).
“During the COVID pandemic, healthcare professionals began to rethink how, when, and where they work,” said Jeff Decker, president of AMN Healthcare’s physician solutions division, adding that he estimates about 52,000 US physicians now work on a locum tenens basis.
“Locum tenens offers relief from the long, inflexible work hours and onerous bureaucratic duties that often cause dissatisfaction and burnout among physicians and other healthcare providers.”
These feelings of dissatisfaction dovetail with findings in recent reports by this news organization based on surveys of physicians about burnout and employment. For example:
- Forty-nine percent of physicians acknowledged feeling burned out, up from 42% 6 years earlier.
- Eighty-three percent of doctors attributed their burnout and/or depression to the job entirely or most of the time.
- Flexibility in work schedules was one of the improvements chosen most often as a potential aid to burnout.
- The leading reasons cited for burnout were the number of bureaucratic tasks and too many hours at work.
Trying Locum Tenens Early in Career
According to AMN Healthcare, 81% of the physicians and APPs in its latest survey said they started taking locum tenens assignments immediately after finishing medical training or in mid-career. Only 19% waited until after retiring from medicine compared with 36% in AMN Healthcare’s 2016 survey.
In the 2024 report, a strong plurality of respondents (47%) said they found locum tenens work more satisfying than permanent healthcare employment. Twelve percent said the opposite, and 30% found the choices about equal.
Even so, it doesn’t appear that locum tenens represents a permanent career path for many. About as many (45%) of physicians and APPs said they would return to full-time employment if progress were made with conditions like hours and burnout, as said they would not (43%).
“Many physicians and other healthcare professionals feel they are being pushed from permanent positions by unsatisfactory work conditions,” Mr. Decker said. “To get them back, employers should offer practice conditions that appeal to today’s providers.”
A version of this article appeared on Medscape.com.
Insane hours and work-driven burnout are increasingly pernicious forces in medical workplaces. They apparently also are helping steer more physicians toward locum tenens, or temporary, assignments.
In its “2024 Survey of Locum Tenens Physicians and Advanced Practice Professionals,” Coppell, Texas–based staffing firm AMN Healthcare asked doctors, nurse practitioners, and physician assistants why they chose locum tenens work.
The reason chosen most often is improving work hours. Eighty-six percent of respondents said that was the “most important” or a “moderately important” factor. Next was addressing work burnout (80% of respondents), followed by unhappiness with compensation (75%), and dissatisfaction with being a full-time employee (71%).
“During the COVID pandemic, healthcare professionals began to rethink how, when, and where they work,” said Jeff Decker, president of AMN Healthcare’s physician solutions division, adding that he estimates about 52,000 US physicians now work on a locum tenens basis.
“Locum tenens offers relief from the long, inflexible work hours and onerous bureaucratic duties that often cause dissatisfaction and burnout among physicians and other healthcare providers.”
These feelings of dissatisfaction dovetail with findings in recent reports by this news organization based on surveys of physicians about burnout and employment. For example:
- Forty-nine percent of physicians acknowledged feeling burned out, up from 42% 6 years earlier.
- Eighty-three percent of doctors attributed their burnout and/or depression to the job entirely or most of the time.
- Flexibility in work schedules was one of the improvements chosen most often as a potential aid to burnout.
- The leading reasons cited for burnout were the number of bureaucratic tasks and too many hours at work.
Trying Locum Tenens Early in Career
According to AMN Healthcare, 81% of the physicians and APPs in its latest survey said they started taking locum tenens assignments immediately after finishing medical training or in mid-career. Only 19% waited until after retiring from medicine compared with 36% in AMN Healthcare’s 2016 survey.
In the 2024 report, a strong plurality of respondents (47%) said they found locum tenens work more satisfying than permanent healthcare employment. Twelve percent said the opposite, and 30% found the choices about equal.
Even so, it doesn’t appear that locum tenens represents a permanent career path for many. About as many (45%) of physicians and APPs said they would return to full-time employment if progress were made with conditions like hours and burnout, as said they would not (43%).
“Many physicians and other healthcare professionals feel they are being pushed from permanent positions by unsatisfactory work conditions,” Mr. Decker said. “To get them back, employers should offer practice conditions that appeal to today’s providers.”
A version of this article appeared on Medscape.com.
Insane hours and work-driven burnout are increasingly pernicious forces in medical workplaces. They apparently also are helping steer more physicians toward locum tenens, or temporary, assignments.
In its “2024 Survey of Locum Tenens Physicians and Advanced Practice Professionals,” Coppell, Texas–based staffing firm AMN Healthcare asked doctors, nurse practitioners, and physician assistants why they chose locum tenens work.
The reason chosen most often is improving work hours. Eighty-six percent of respondents said that was the “most important” or a “moderately important” factor. Next was addressing work burnout (80% of respondents), followed by unhappiness with compensation (75%), and dissatisfaction with being a full-time employee (71%).
“During the COVID pandemic, healthcare professionals began to rethink how, when, and where they work,” said Jeff Decker, president of AMN Healthcare’s physician solutions division, adding that he estimates about 52,000 US physicians now work on a locum tenens basis.
“Locum tenens offers relief from the long, inflexible work hours and onerous bureaucratic duties that often cause dissatisfaction and burnout among physicians and other healthcare providers.”
These feelings of dissatisfaction dovetail with findings in recent reports by this news organization based on surveys of physicians about burnout and employment. For example:
- Forty-nine percent of physicians acknowledged feeling burned out, up from 42% 6 years earlier.
- Eighty-three percent of doctors attributed their burnout and/or depression to the job entirely or most of the time.
- Flexibility in work schedules was one of the improvements chosen most often as a potential aid to burnout.
- The leading reasons cited for burnout were the number of bureaucratic tasks and too many hours at work.
Trying Locum Tenens Early in Career
According to AMN Healthcare, 81% of the physicians and APPs in its latest survey said they started taking locum tenens assignments immediately after finishing medical training or in mid-career. Only 19% waited until after retiring from medicine compared with 36% in AMN Healthcare’s 2016 survey.
In the 2024 report, a strong plurality of respondents (47%) said they found locum tenens work more satisfying than permanent healthcare employment. Twelve percent said the opposite, and 30% found the choices about equal.
Even so, it doesn’t appear that locum tenens represents a permanent career path for many. About as many (45%) of physicians and APPs said they would return to full-time employment if progress were made with conditions like hours and burnout, as said they would not (43%).
“Many physicians and other healthcare professionals feel they are being pushed from permanent positions by unsatisfactory work conditions,” Mr. Decker said. “To get them back, employers should offer practice conditions that appeal to today’s providers.”
A version of this article appeared on Medscape.com.
This Tech Will Change Your Practice Sooner Than You Think
Medical innovations don’t happen overnight — but in today’s digital world, they happen pretty fast. Some are advancing faster than you think.
1. Artificial Intelligence (AI) Medical Scribes
You may already be using this or, at the very least, have heard about it.
Physician burnout is a growing problem, with many doctors spending 2 hours on paperwork for every hour with patients. But some doctors, such as Gregory Ator, MD, chief medical informatics officer at the University of Kansas Medical Center, Kansas City, Kansas, have found a better way.
“I have been using it for 9 months now, and it truly is a life changer,” Dr. Ator said of Abridge, an AI helper that transcribes and summarizes his conversations with patients. “Now, I go into the room, place my phone just about anywhere, and I can just listen.” He estimated that the tech saves him between 3 and 10 minutes per patient. “At 20 patients a day, that saves me around 2 hours,” he said.
Bonus: Patients “get a doctor’s full attention instead of just looking at the top of his head while they play with the computer,” Dr. Ator said. “I have yet to have a patient who didn’t think that was a positive thing.”
Several companies are already selling these AI devices, including Ambience Healthcare, Augmedix, Nuance, and Suki, and they offer more than just transcriptions, said John D. Halamka, MD, president of Mayo Clinic Platform, who oversees Mayo’s adoption of AI. They also generate notes for treatment and billing and update data in the electronic health record.
“It’s preparation of documentation based on ambient listening of doctor-patient conversations,” Dr. Halamka explained. “I’m very optimistic about the use of emerging AI technologies to enable every clinician to practice at the top of their license.”
Patricia Garcia, MD, associate clinical information officer for ambulatory care at Stanford Health Care, has spent much of the last year co-running the medical center’s pilot program for AI scribes, and she’s so impressed with the technology that she “expects it’ll become more widely available as an option for any clinician that wants to use it in the next 12-18 months.”
2. Three-Dimensional (3D) Printing
Although 3D-printed organs may not happen anytime soon, the future is here for some 3D-printed prosthetics and implants — everything from dentures to spinal implants to prosthetic fingers and noses.
“In the next few years, I see rapid growth in the use of 3D printing technology across orthopedic surgery,” said Rishin J. Kadakia, MD, an orthopedic surgeon in Atlanta. “It’s becoming more common not just at large academic institutions. More and more providers will turn to using 3D printing technology to help tackle challenging cases that previously did not have good solutions.”
Dr. Kadakia has experienced this firsthand with his patients at the Emory Orthopaedics & Spine Center. One female patient developed talar avascular necrosis due to a bone break she’d sustained in a serious car crash. An ankle and subtalar joint fusion would repair the damage but limit her mobility and change her gait. So instead, in August of 2021, Dr. Kadakia and fellow orthopedic surgeon Jason Bariteau, MD, created for her a 3D-printed cobalt chrome talus implant.
“It provided an opportunity for her to keep her ankle’s range of motion, and also mobilize faster than with a subtalar and ankle joint fusion,” said Dr. Kadakia.
The technology is also playing a role in customized medical devices — patient-specific tools for greater precision — and 3D-printed anatomical models, built to the exact specifications of individual patients. Mayo Clinic already has 3D modeling units in three states, and other hospitals are following suit. The models not only help doctors prepare for complicated surgeries but also can dramatically cut down on costs. A 2021 study from Durham University reported that 3D models helped reduce surgery time by between 1.5 and 2.5 hours in lengthy procedures.
3. Drones
For patients who can’t make it to a pharmacy to pick up their prescriptions, either because of distance or lack of transportation, drones — which can deliver medications onto a customer’s back yard or front porch — offer a compelling solution.
Several companies and hospitals are already experimenting with drones, like WellSpan Health in Pennsylvania, Amazon Pharmacy, and the Cleveland Clinic, which announced a partnership with drone delivery company Zipline and plans to begin prescription deliveries across Northeast Ohio by 2025.
Healthcare systems are just beginning to explore the potential of drone deliveries, for everything from lab samples to medical and surgical supplies — even defibrillators that could arrive at an ailing patient’s front door before an emergency medical technician arrives.
“For many providers, when you take a sample from a patient, that sample waits around for hours until a courier picks up all of the facility’s samples and drives them to an outside facility for processing,” said Hillary Brendzel, head of Zipline’s US Healthcare Practice.
According to a 2022 survey from American Nurse Journal, 71% of nurses said that medical courier delays and errors negatively affected their ability to provide patient care. But with drone delivery, “lab samples can be sent for processing immediately, on-demand, resulting in faster diagnosis, treatment, and ultimately better outcomes,” said Ms. Brendzel.
4. Portable Ultrasound
Within the next 2 years, portable ultrasound — pocket-sized devices that connect to a smartphone or tablet — will become the “21st-century stethoscope,” said Abhilash Hareendranathan, PhD, assistant professor in the Department of Radiology and Diagnostic Imaging at the University of Alberta, in Edmonton, Alberta, Canada.
AI can make these devices easy to use, allowing clinicians with minimal imaging training to capture clear images and understand the results. Dr. Hareendranathan developed the Ultrasound Arm Injury Detection tool, a portable ultrasound that uses AI to detect fracture.
“We plan to introduce this technology in emergency departments, where it could be used by triage nurses to perform quick examinations to detect fractures of the wrist, elbow, or shoulder,” he said.
More pocket-sized scanners like these could “reshape the way diagnostic care is provided in rural and remote communities,” Dr. Hareendranathan said, and will “reduce wait times in crowded emergency departments.” Bill Gates believes enough in portable ultrasound that last September, the Bill & Melinda Gates Foundation granted $44 million to GE HealthCare to develop the technology for under-resourced communities.
5. Virtual Reality (VR)
When RelieVRx became the first US Food and Drug Administration (FDA)–approved VR therapy for chronic back pain in 2021, the technology was used in just a handful of Veterans Affairs (VA) facilities. But today, thousands of VR headsets have been deployed to more than 160 VA medical centers and clinics across the country.
“The VR experiences encompass pain neuroscience education, mindfulness, pleasant and relaxing distraction, and key skills to calm the nervous system,” said Beth Darnall, PhD, director of the Stanford Pain Relief Innovations Lab, who helped design the RelieVRx. She expects VR to go mainstream soon, not just because of increasing evidence that it works but also thanks to the Centers for Medicare & Medicaid Services, which recently issued a Healthcare Common Procedure Coding System code for VR. “This billing infrastructure will encourage adoption and uptake,” she said.
Hundreds of hospitals across the United States have already adopted the technology, for everything from childbirth pain to wound debridement, said Josh Sackman, the president and cofounder of AppliedVR, the company that developed RelieVRx.
“Over the next few years, we may see hundreds more deploy unique applications [for VR] that can handle multiple clinical indications,” he said. “Given the modality’s ability to scale and reduce reliance on pharmacological interventions, it has the power to improve the cost and quality of care.”
Hospital systems like Geisinger and Cedars-Sinai are already finding unique ways to implement the technology, he said, like using VR to reduce “scanxiety” during imaging service.
Other VR innovations are already being introduced, from the Smileyscope, a VR device for children that’s been proven to lessen the pain of a blood draw or intravenous insertion (it was cleared by the FDA last November) to several VR platforms launched by Cedars-Sinai in recent months, for applications that range from gastrointestinal issues to mental health therapy. “There may already be a thousand hospitals using VR in some capacity,” said Brennan Spiegel, MD, director of Health Services Research at Cedars-Sinai.
A version of this article appeared on Medscape.com.
Medical innovations don’t happen overnight — but in today’s digital world, they happen pretty fast. Some are advancing faster than you think.
1. Artificial Intelligence (AI) Medical Scribes
You may already be using this or, at the very least, have heard about it.
Physician burnout is a growing problem, with many doctors spending 2 hours on paperwork for every hour with patients. But some doctors, such as Gregory Ator, MD, chief medical informatics officer at the University of Kansas Medical Center, Kansas City, Kansas, have found a better way.
“I have been using it for 9 months now, and it truly is a life changer,” Dr. Ator said of Abridge, an AI helper that transcribes and summarizes his conversations with patients. “Now, I go into the room, place my phone just about anywhere, and I can just listen.” He estimated that the tech saves him between 3 and 10 minutes per patient. “At 20 patients a day, that saves me around 2 hours,” he said.
Bonus: Patients “get a doctor’s full attention instead of just looking at the top of his head while they play with the computer,” Dr. Ator said. “I have yet to have a patient who didn’t think that was a positive thing.”
Several companies are already selling these AI devices, including Ambience Healthcare, Augmedix, Nuance, and Suki, and they offer more than just transcriptions, said John D. Halamka, MD, president of Mayo Clinic Platform, who oversees Mayo’s adoption of AI. They also generate notes for treatment and billing and update data in the electronic health record.
“It’s preparation of documentation based on ambient listening of doctor-patient conversations,” Dr. Halamka explained. “I’m very optimistic about the use of emerging AI technologies to enable every clinician to practice at the top of their license.”
Patricia Garcia, MD, associate clinical information officer for ambulatory care at Stanford Health Care, has spent much of the last year co-running the medical center’s pilot program for AI scribes, and she’s so impressed with the technology that she “expects it’ll become more widely available as an option for any clinician that wants to use it in the next 12-18 months.”
2. Three-Dimensional (3D) Printing
Although 3D-printed organs may not happen anytime soon, the future is here for some 3D-printed prosthetics and implants — everything from dentures to spinal implants to prosthetic fingers and noses.
“In the next few years, I see rapid growth in the use of 3D printing technology across orthopedic surgery,” said Rishin J. Kadakia, MD, an orthopedic surgeon in Atlanta. “It’s becoming more common not just at large academic institutions. More and more providers will turn to using 3D printing technology to help tackle challenging cases that previously did not have good solutions.”
Dr. Kadakia has experienced this firsthand with his patients at the Emory Orthopaedics & Spine Center. One female patient developed talar avascular necrosis due to a bone break she’d sustained in a serious car crash. An ankle and subtalar joint fusion would repair the damage but limit her mobility and change her gait. So instead, in August of 2021, Dr. Kadakia and fellow orthopedic surgeon Jason Bariteau, MD, created for her a 3D-printed cobalt chrome talus implant.
“It provided an opportunity for her to keep her ankle’s range of motion, and also mobilize faster than with a subtalar and ankle joint fusion,” said Dr. Kadakia.
The technology is also playing a role in customized medical devices — patient-specific tools for greater precision — and 3D-printed anatomical models, built to the exact specifications of individual patients. Mayo Clinic already has 3D modeling units in three states, and other hospitals are following suit. The models not only help doctors prepare for complicated surgeries but also can dramatically cut down on costs. A 2021 study from Durham University reported that 3D models helped reduce surgery time by between 1.5 and 2.5 hours in lengthy procedures.
3. Drones
For patients who can’t make it to a pharmacy to pick up their prescriptions, either because of distance or lack of transportation, drones — which can deliver medications onto a customer’s back yard or front porch — offer a compelling solution.
Several companies and hospitals are already experimenting with drones, like WellSpan Health in Pennsylvania, Amazon Pharmacy, and the Cleveland Clinic, which announced a partnership with drone delivery company Zipline and plans to begin prescription deliveries across Northeast Ohio by 2025.
Healthcare systems are just beginning to explore the potential of drone deliveries, for everything from lab samples to medical and surgical supplies — even defibrillators that could arrive at an ailing patient’s front door before an emergency medical technician arrives.
“For many providers, when you take a sample from a patient, that sample waits around for hours until a courier picks up all of the facility’s samples and drives them to an outside facility for processing,” said Hillary Brendzel, head of Zipline’s US Healthcare Practice.
According to a 2022 survey from American Nurse Journal, 71% of nurses said that medical courier delays and errors negatively affected their ability to provide patient care. But with drone delivery, “lab samples can be sent for processing immediately, on-demand, resulting in faster diagnosis, treatment, and ultimately better outcomes,” said Ms. Brendzel.
4. Portable Ultrasound
Within the next 2 years, portable ultrasound — pocket-sized devices that connect to a smartphone or tablet — will become the “21st-century stethoscope,” said Abhilash Hareendranathan, PhD, assistant professor in the Department of Radiology and Diagnostic Imaging at the University of Alberta, in Edmonton, Alberta, Canada.
AI can make these devices easy to use, allowing clinicians with minimal imaging training to capture clear images and understand the results. Dr. Hareendranathan developed the Ultrasound Arm Injury Detection tool, a portable ultrasound that uses AI to detect fracture.
“We plan to introduce this technology in emergency departments, where it could be used by triage nurses to perform quick examinations to detect fractures of the wrist, elbow, or shoulder,” he said.
More pocket-sized scanners like these could “reshape the way diagnostic care is provided in rural and remote communities,” Dr. Hareendranathan said, and will “reduce wait times in crowded emergency departments.” Bill Gates believes enough in portable ultrasound that last September, the Bill & Melinda Gates Foundation granted $44 million to GE HealthCare to develop the technology for under-resourced communities.
5. Virtual Reality (VR)
When RelieVRx became the first US Food and Drug Administration (FDA)–approved VR therapy for chronic back pain in 2021, the technology was used in just a handful of Veterans Affairs (VA) facilities. But today, thousands of VR headsets have been deployed to more than 160 VA medical centers and clinics across the country.
“The VR experiences encompass pain neuroscience education, mindfulness, pleasant and relaxing distraction, and key skills to calm the nervous system,” said Beth Darnall, PhD, director of the Stanford Pain Relief Innovations Lab, who helped design the RelieVRx. She expects VR to go mainstream soon, not just because of increasing evidence that it works but also thanks to the Centers for Medicare & Medicaid Services, which recently issued a Healthcare Common Procedure Coding System code for VR. “This billing infrastructure will encourage adoption and uptake,” she said.
Hundreds of hospitals across the United States have already adopted the technology, for everything from childbirth pain to wound debridement, said Josh Sackman, the president and cofounder of AppliedVR, the company that developed RelieVRx.
“Over the next few years, we may see hundreds more deploy unique applications [for VR] that can handle multiple clinical indications,” he said. “Given the modality’s ability to scale and reduce reliance on pharmacological interventions, it has the power to improve the cost and quality of care.”
Hospital systems like Geisinger and Cedars-Sinai are already finding unique ways to implement the technology, he said, like using VR to reduce “scanxiety” during imaging service.
Other VR innovations are already being introduced, from the Smileyscope, a VR device for children that’s been proven to lessen the pain of a blood draw or intravenous insertion (it was cleared by the FDA last November) to several VR platforms launched by Cedars-Sinai in recent months, for applications that range from gastrointestinal issues to mental health therapy. “There may already be a thousand hospitals using VR in some capacity,” said Brennan Spiegel, MD, director of Health Services Research at Cedars-Sinai.
A version of this article appeared on Medscape.com.
Medical innovations don’t happen overnight — but in today’s digital world, they happen pretty fast. Some are advancing faster than you think.
1. Artificial Intelligence (AI) Medical Scribes
You may already be using this or, at the very least, have heard about it.
Physician burnout is a growing problem, with many doctors spending 2 hours on paperwork for every hour with patients. But some doctors, such as Gregory Ator, MD, chief medical informatics officer at the University of Kansas Medical Center, Kansas City, Kansas, have found a better way.
“I have been using it for 9 months now, and it truly is a life changer,” Dr. Ator said of Abridge, an AI helper that transcribes and summarizes his conversations with patients. “Now, I go into the room, place my phone just about anywhere, and I can just listen.” He estimated that the tech saves him between 3 and 10 minutes per patient. “At 20 patients a day, that saves me around 2 hours,” he said.
Bonus: Patients “get a doctor’s full attention instead of just looking at the top of his head while they play with the computer,” Dr. Ator said. “I have yet to have a patient who didn’t think that was a positive thing.”
Several companies are already selling these AI devices, including Ambience Healthcare, Augmedix, Nuance, and Suki, and they offer more than just transcriptions, said John D. Halamka, MD, president of Mayo Clinic Platform, who oversees Mayo’s adoption of AI. They also generate notes for treatment and billing and update data in the electronic health record.
“It’s preparation of documentation based on ambient listening of doctor-patient conversations,” Dr. Halamka explained. “I’m very optimistic about the use of emerging AI technologies to enable every clinician to practice at the top of their license.”
Patricia Garcia, MD, associate clinical information officer for ambulatory care at Stanford Health Care, has spent much of the last year co-running the medical center’s pilot program for AI scribes, and she’s so impressed with the technology that she “expects it’ll become more widely available as an option for any clinician that wants to use it in the next 12-18 months.”
2. Three-Dimensional (3D) Printing
Although 3D-printed organs may not happen anytime soon, the future is here for some 3D-printed prosthetics and implants — everything from dentures to spinal implants to prosthetic fingers and noses.
“In the next few years, I see rapid growth in the use of 3D printing technology across orthopedic surgery,” said Rishin J. Kadakia, MD, an orthopedic surgeon in Atlanta. “It’s becoming more common not just at large academic institutions. More and more providers will turn to using 3D printing technology to help tackle challenging cases that previously did not have good solutions.”
Dr. Kadakia has experienced this firsthand with his patients at the Emory Orthopaedics & Spine Center. One female patient developed talar avascular necrosis due to a bone break she’d sustained in a serious car crash. An ankle and subtalar joint fusion would repair the damage but limit her mobility and change her gait. So instead, in August of 2021, Dr. Kadakia and fellow orthopedic surgeon Jason Bariteau, MD, created for her a 3D-printed cobalt chrome talus implant.
“It provided an opportunity for her to keep her ankle’s range of motion, and also mobilize faster than with a subtalar and ankle joint fusion,” said Dr. Kadakia.
The technology is also playing a role in customized medical devices — patient-specific tools for greater precision — and 3D-printed anatomical models, built to the exact specifications of individual patients. Mayo Clinic already has 3D modeling units in three states, and other hospitals are following suit. The models not only help doctors prepare for complicated surgeries but also can dramatically cut down on costs. A 2021 study from Durham University reported that 3D models helped reduce surgery time by between 1.5 and 2.5 hours in lengthy procedures.
3. Drones
For patients who can’t make it to a pharmacy to pick up their prescriptions, either because of distance or lack of transportation, drones — which can deliver medications onto a customer’s back yard or front porch — offer a compelling solution.
Several companies and hospitals are already experimenting with drones, like WellSpan Health in Pennsylvania, Amazon Pharmacy, and the Cleveland Clinic, which announced a partnership with drone delivery company Zipline and plans to begin prescription deliveries across Northeast Ohio by 2025.
Healthcare systems are just beginning to explore the potential of drone deliveries, for everything from lab samples to medical and surgical supplies — even defibrillators that could arrive at an ailing patient’s front door before an emergency medical technician arrives.
“For many providers, when you take a sample from a patient, that sample waits around for hours until a courier picks up all of the facility’s samples and drives them to an outside facility for processing,” said Hillary Brendzel, head of Zipline’s US Healthcare Practice.
According to a 2022 survey from American Nurse Journal, 71% of nurses said that medical courier delays and errors negatively affected their ability to provide patient care. But with drone delivery, “lab samples can be sent for processing immediately, on-demand, resulting in faster diagnosis, treatment, and ultimately better outcomes,” said Ms. Brendzel.
4. Portable Ultrasound
Within the next 2 years, portable ultrasound — pocket-sized devices that connect to a smartphone or tablet — will become the “21st-century stethoscope,” said Abhilash Hareendranathan, PhD, assistant professor in the Department of Radiology and Diagnostic Imaging at the University of Alberta, in Edmonton, Alberta, Canada.
AI can make these devices easy to use, allowing clinicians with minimal imaging training to capture clear images and understand the results. Dr. Hareendranathan developed the Ultrasound Arm Injury Detection tool, a portable ultrasound that uses AI to detect fracture.
“We plan to introduce this technology in emergency departments, where it could be used by triage nurses to perform quick examinations to detect fractures of the wrist, elbow, or shoulder,” he said.
More pocket-sized scanners like these could “reshape the way diagnostic care is provided in rural and remote communities,” Dr. Hareendranathan said, and will “reduce wait times in crowded emergency departments.” Bill Gates believes enough in portable ultrasound that last September, the Bill & Melinda Gates Foundation granted $44 million to GE HealthCare to develop the technology for under-resourced communities.
5. Virtual Reality (VR)
When RelieVRx became the first US Food and Drug Administration (FDA)–approved VR therapy for chronic back pain in 2021, the technology was used in just a handful of Veterans Affairs (VA) facilities. But today, thousands of VR headsets have been deployed to more than 160 VA medical centers and clinics across the country.
“The VR experiences encompass pain neuroscience education, mindfulness, pleasant and relaxing distraction, and key skills to calm the nervous system,” said Beth Darnall, PhD, director of the Stanford Pain Relief Innovations Lab, who helped design the RelieVRx. She expects VR to go mainstream soon, not just because of increasing evidence that it works but also thanks to the Centers for Medicare & Medicaid Services, which recently issued a Healthcare Common Procedure Coding System code for VR. “This billing infrastructure will encourage adoption and uptake,” she said.
Hundreds of hospitals across the United States have already adopted the technology, for everything from childbirth pain to wound debridement, said Josh Sackman, the president and cofounder of AppliedVR, the company that developed RelieVRx.
“Over the next few years, we may see hundreds more deploy unique applications [for VR] that can handle multiple clinical indications,” he said. “Given the modality’s ability to scale and reduce reliance on pharmacological interventions, it has the power to improve the cost and quality of care.”
Hospital systems like Geisinger and Cedars-Sinai are already finding unique ways to implement the technology, he said, like using VR to reduce “scanxiety” during imaging service.
Other VR innovations are already being introduced, from the Smileyscope, a VR device for children that’s been proven to lessen the pain of a blood draw or intravenous insertion (it was cleared by the FDA last November) to several VR platforms launched by Cedars-Sinai in recent months, for applications that range from gastrointestinal issues to mental health therapy. “There may already be a thousand hospitals using VR in some capacity,” said Brennan Spiegel, MD, director of Health Services Research at Cedars-Sinai.
A version of this article appeared on Medscape.com.
Do No Harm: What Smoldering Myeloma Teaches Us
My approach to treating SMM takes into account what its history can teach us about 1) how advancements in imaging and diagnostic reclassifications can revise the entire natural history of a disease, and 2) how evidence generated by even the best of studies may have an expiration date.
Much of what we know about SMM today dates to a pivotal study by Robert A. Kyle, MD, and colleagues, published in 2007. That inspirational team of investigators followed people diagnosed with SMM from 1970 to 1995 and established the first natural history of the condition. Their monumental effort and the data and conclusions it generated (eg,10% risk annually of SMM becoming MM for the first 5 years) are still cited today in references, papers, and slide sets.
Despite the seminal importance of this work, from today’s perspective the 2007 study might just as well have been describing a different disease. Back then people were diagnosed with SMM if their blood work detected a monoclonal protein and a follow-up bone marrow biopsy found at least 10% plasma cells (or a monoclonal protein exceeding 3g/dL). If there were no signs of end-organ damage (ie, no anemia or kidney problems) and an x-ray showed no fractures or lesions in the bones, the diagnosis was determined to be SMM.
What’s different in 2024? First and foremost: advanced, highly sensitive imaging techniques. MRIs can pick up small lytic lesions (and even the precursor to lytic lesions) that would not appear on an x-ray. In fact, relying solely on x-rays risks missing half of the lytic lesions.
Therefore, using the same criteria, many people who in the past were diagnosed with SMM would today be diagnosed with MM. Furthermore, in 2014 a diagnostic change reclassified people’s diagnosis from the highest risk category of SMM to the category of active MM.
Due to these scientific advances and classification changes, I believe that the natural history of SMM is unknown. Risk stratification models for SMM derived from data sets of people who had not undergone rigorous advanced imaging likely are skewed by data from people who had MM. In addition, current risk stratification models have very poor concordance with each other. I routinely see people whose 2-year risk according to different models varies by more than 30%-40%.
All this information tells us that SMM today is more indolent than the SMM of the past. Paradoxically, however, our therapies keep getting more and more aggressive, exposing this vulnerable group of people to intense treatment regimens that they may not require. Therapies tested on people diagnosed with SMM include an aggressive three-drug regimen, autologous stem cell transplant, and 2 years of additional therapy, as well as, more recently CAR T-cell therapy which so far has at least a 4%-5% treatment-related mortality risk in people with myeloma and a strong signal for secondary cancer risk. Other trials are testing bispecific therapies such as talquetamab, a drug which in my experience causes horrendous skin toxicity, profound weight loss, and one’s nails to fall off.
Doctors routinely keep showing slides from Kyle’s pivotal work to describe the natural history of SMM and to justify the need for treatment, and trials continue to use outdated progression prediction models. In my opinion, as people with MM keep living longer and treatments for MM keep getting better, the threshold for intervening with asymptomatic, healthy people with SMM should be getting higher, not lower.
I strongly believe that the current landscape of SMM treatment exemplifies good intentions leading to bad outcomes. A routine blood test in a completely healthy person that finds elevated total protein in the blood could culminate in well-intentioned but aggressive therapies that can lead to many serious side effects. (I repeat: Secondary cancers and deaths from infections have all occurred in SMM trials.)
With no control arm, we simply don’t know how well these people might have fared without any therapy. For all we know, treatment may have shortened their lives due to complications up to and including death — all because of a blood test often conducted for reasons that have no evidentiary basis.
For example, plasma cell diseases are not linked to low bone density or auto-immune diseases, yet these labs are sent routinely as part of a workup for those conditions, leading to increasing anxiety and costs.
So, what is my approach? When treating people with SMM, I hold nuanced discussions of this data to help prioritize and reach informed decisions. After our honest conversation about the limitations of SMM models, older data, and the limitations of prospective data studying pharmacological treatment, almost no one signs up for treatment.
I want these people to stay safe, and I’m proud to be a part of a trial (SPOTLIGHT, NCT06212323) that aims to show prospectively that these people can be watched off treatment with monitoring via advanced imaging modalities.
In conclusion: SMM teaches us how, even in the absence of pharmacological interventions, the natural history of a disease can change over time, simply via better imaging techniques and changes in diagnostic classifications. Unfortunately, SMM also illustrates how good intentions can lead to harm.
Dr. Mohyuddin is assistant professor in the multiple myeloma program at the Huntsman Cancer Institute at the University of Utah in Salt Lake City.
My approach to treating SMM takes into account what its history can teach us about 1) how advancements in imaging and diagnostic reclassifications can revise the entire natural history of a disease, and 2) how evidence generated by even the best of studies may have an expiration date.
Much of what we know about SMM today dates to a pivotal study by Robert A. Kyle, MD, and colleagues, published in 2007. That inspirational team of investigators followed people diagnosed with SMM from 1970 to 1995 and established the first natural history of the condition. Their monumental effort and the data and conclusions it generated (eg,10% risk annually of SMM becoming MM for the first 5 years) are still cited today in references, papers, and slide sets.
Despite the seminal importance of this work, from today’s perspective the 2007 study might just as well have been describing a different disease. Back then people were diagnosed with SMM if their blood work detected a monoclonal protein and a follow-up bone marrow biopsy found at least 10% plasma cells (or a monoclonal protein exceeding 3g/dL). If there were no signs of end-organ damage (ie, no anemia or kidney problems) and an x-ray showed no fractures or lesions in the bones, the diagnosis was determined to be SMM.
What’s different in 2024? First and foremost: advanced, highly sensitive imaging techniques. MRIs can pick up small lytic lesions (and even the precursor to lytic lesions) that would not appear on an x-ray. In fact, relying solely on x-rays risks missing half of the lytic lesions.
Therefore, using the same criteria, many people who in the past were diagnosed with SMM would today be diagnosed with MM. Furthermore, in 2014 a diagnostic change reclassified people’s diagnosis from the highest risk category of SMM to the category of active MM.
Due to these scientific advances and classification changes, I believe that the natural history of SMM is unknown. Risk stratification models for SMM derived from data sets of people who had not undergone rigorous advanced imaging likely are skewed by data from people who had MM. In addition, current risk stratification models have very poor concordance with each other. I routinely see people whose 2-year risk according to different models varies by more than 30%-40%.
All this information tells us that SMM today is more indolent than the SMM of the past. Paradoxically, however, our therapies keep getting more and more aggressive, exposing this vulnerable group of people to intense treatment regimens that they may not require. Therapies tested on people diagnosed with SMM include an aggressive three-drug regimen, autologous stem cell transplant, and 2 years of additional therapy, as well as, more recently CAR T-cell therapy which so far has at least a 4%-5% treatment-related mortality risk in people with myeloma and a strong signal for secondary cancer risk. Other trials are testing bispecific therapies such as talquetamab, a drug which in my experience causes horrendous skin toxicity, profound weight loss, and one’s nails to fall off.
Doctors routinely keep showing slides from Kyle’s pivotal work to describe the natural history of SMM and to justify the need for treatment, and trials continue to use outdated progression prediction models. In my opinion, as people with MM keep living longer and treatments for MM keep getting better, the threshold for intervening with asymptomatic, healthy people with SMM should be getting higher, not lower.
I strongly believe that the current landscape of SMM treatment exemplifies good intentions leading to bad outcomes. A routine blood test in a completely healthy person that finds elevated total protein in the blood could culminate in well-intentioned but aggressive therapies that can lead to many serious side effects. (I repeat: Secondary cancers and deaths from infections have all occurred in SMM trials.)
With no control arm, we simply don’t know how well these people might have fared without any therapy. For all we know, treatment may have shortened their lives due to complications up to and including death — all because of a blood test often conducted for reasons that have no evidentiary basis.
For example, plasma cell diseases are not linked to low bone density or auto-immune diseases, yet these labs are sent routinely as part of a workup for those conditions, leading to increasing anxiety and costs.
So, what is my approach? When treating people with SMM, I hold nuanced discussions of this data to help prioritize and reach informed decisions. After our honest conversation about the limitations of SMM models, older data, and the limitations of prospective data studying pharmacological treatment, almost no one signs up for treatment.
I want these people to stay safe, and I’m proud to be a part of a trial (SPOTLIGHT, NCT06212323) that aims to show prospectively that these people can be watched off treatment with monitoring via advanced imaging modalities.
In conclusion: SMM teaches us how, even in the absence of pharmacological interventions, the natural history of a disease can change over time, simply via better imaging techniques and changes in diagnostic classifications. Unfortunately, SMM also illustrates how good intentions can lead to harm.
Dr. Mohyuddin is assistant professor in the multiple myeloma program at the Huntsman Cancer Institute at the University of Utah in Salt Lake City.
My approach to treating SMM takes into account what its history can teach us about 1) how advancements in imaging and diagnostic reclassifications can revise the entire natural history of a disease, and 2) how evidence generated by even the best of studies may have an expiration date.
Much of what we know about SMM today dates to a pivotal study by Robert A. Kyle, MD, and colleagues, published in 2007. That inspirational team of investigators followed people diagnosed with SMM from 1970 to 1995 and established the first natural history of the condition. Their monumental effort and the data and conclusions it generated (eg,10% risk annually of SMM becoming MM for the first 5 years) are still cited today in references, papers, and slide sets.
Despite the seminal importance of this work, from today’s perspective the 2007 study might just as well have been describing a different disease. Back then people were diagnosed with SMM if their blood work detected a monoclonal protein and a follow-up bone marrow biopsy found at least 10% plasma cells (or a monoclonal protein exceeding 3g/dL). If there were no signs of end-organ damage (ie, no anemia or kidney problems) and an x-ray showed no fractures or lesions in the bones, the diagnosis was determined to be SMM.
What’s different in 2024? First and foremost: advanced, highly sensitive imaging techniques. MRIs can pick up small lytic lesions (and even the precursor to lytic lesions) that would not appear on an x-ray. In fact, relying solely on x-rays risks missing half of the lytic lesions.
Therefore, using the same criteria, many people who in the past were diagnosed with SMM would today be diagnosed with MM. Furthermore, in 2014 a diagnostic change reclassified people’s diagnosis from the highest risk category of SMM to the category of active MM.
Due to these scientific advances and classification changes, I believe that the natural history of SMM is unknown. Risk stratification models for SMM derived from data sets of people who had not undergone rigorous advanced imaging likely are skewed by data from people who had MM. In addition, current risk stratification models have very poor concordance with each other. I routinely see people whose 2-year risk according to different models varies by more than 30%-40%.
All this information tells us that SMM today is more indolent than the SMM of the past. Paradoxically, however, our therapies keep getting more and more aggressive, exposing this vulnerable group of people to intense treatment regimens that they may not require. Therapies tested on people diagnosed with SMM include an aggressive three-drug regimen, autologous stem cell transplant, and 2 years of additional therapy, as well as, more recently CAR T-cell therapy which so far has at least a 4%-5% treatment-related mortality risk in people with myeloma and a strong signal for secondary cancer risk. Other trials are testing bispecific therapies such as talquetamab, a drug which in my experience causes horrendous skin toxicity, profound weight loss, and one’s nails to fall off.
Doctors routinely keep showing slides from Kyle’s pivotal work to describe the natural history of SMM and to justify the need for treatment, and trials continue to use outdated progression prediction models. In my opinion, as people with MM keep living longer and treatments for MM keep getting better, the threshold for intervening with asymptomatic, healthy people with SMM should be getting higher, not lower.
I strongly believe that the current landscape of SMM treatment exemplifies good intentions leading to bad outcomes. A routine blood test in a completely healthy person that finds elevated total protein in the blood could culminate in well-intentioned but aggressive therapies that can lead to many serious side effects. (I repeat: Secondary cancers and deaths from infections have all occurred in SMM trials.)
With no control arm, we simply don’t know how well these people might have fared without any therapy. For all we know, treatment may have shortened their lives due to complications up to and including death — all because of a blood test often conducted for reasons that have no evidentiary basis.
For example, plasma cell diseases are not linked to low bone density or auto-immune diseases, yet these labs are sent routinely as part of a workup for those conditions, leading to increasing anxiety and costs.
So, what is my approach? When treating people with SMM, I hold nuanced discussions of this data to help prioritize and reach informed decisions. After our honest conversation about the limitations of SMM models, older data, and the limitations of prospective data studying pharmacological treatment, almost no one signs up for treatment.
I want these people to stay safe, and I’m proud to be a part of a trial (SPOTLIGHT, NCT06212323) that aims to show prospectively that these people can be watched off treatment with monitoring via advanced imaging modalities.
In conclusion: SMM teaches us how, even in the absence of pharmacological interventions, the natural history of a disease can change over time, simply via better imaging techniques and changes in diagnostic classifications. Unfortunately, SMM also illustrates how good intentions can lead to harm.
Dr. Mohyuddin is assistant professor in the multiple myeloma program at the Huntsman Cancer Institute at the University of Utah in Salt Lake City.
Working Hard or Work Addiction — Have You Crossed the Line?
When child psychiatrist Javeed Sukhera, MD, PhD, was a few years into his career, he found himself doing it all. “I was in a leadership role academically at the medical school, I had a leadership role at the hospital, and I was seeing as many patients as I could. I could work all day every day.”
“It still wouldn’t have been enough,” he said.
Whenever there was a shift available, Dr. Sukhera would take it. His job was stressful, but as a new physician with a young family, he saw this obsession with work as necessary. “I began to cope with the stress from work by doing extra work and feeling like I needed to be everywhere. It was like I became a hamster on a spinning wheel. I was just running, running, running.”
Things shifted for Dr. Sukhera when he realized that while he was emotionally available for the children who were his patients, at home, his own children weren’t getting the best of him. “There was a specific moment when I thought my son was afraid of me,” he said. “I just stopped and realized that there was something happening that I needed to break. I needed to make a change.”
Dr. Sukhera, now chair of psychiatry at the Institute of Living and chief of the Department of Psychiatry at Hartford Hospital, Hartford, Connecticut, believes what he experienced was a steep fall into work addiction.
What Does Work Addiction Look Like for Doctors?
Behavioral addictions are fairly new in the addiction space. When gambling disorder, the first and only behavioral addiction in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, was added in 2013, it was seen as a “breakthrough addiction,” said Mark D. Griffiths, PhD, a leading behavioral addiction researcher and a distinguished professor at Nottingham Trent University.
Because there is not enough evidence yet to classify work addiction as a formal diagnosis, there is no clear consensus on how to define it. To further complicate things, the terms “workaholism” and “work addiction” can be used interchangeably, and some experts say the two are not the same, though they can overlap.
That said, a 2018 review of literature from several countries found that work addiction “fits very well into recently postulated criteria for conceptualization of a behavioral addiction.
“If you accept that gambling can be genuinely addictive, then there’s no reason to think that something like work, exercise, or video game playing couldn’t be an addiction as well,” said Dr. Griffiths.
“The neurobiology of addiction is that we get drawn to something that gives us a dopamine hit,” Dr. Sukhera added. “But to do that all day, every day, has consequences. It drains our emotional reserves, and it can greatly impact our relationships.”
On top of that, work addiction has been linked with poor sleep, poor cardiovascular health, high blood pressure, burnout, the development of autoimmune disorders, and other health issues.
Physicians are particularly susceptible. Doctors, after all, are expected to work long hours and put their patients’ needs first, even at the expense of their own health and well-being.
“Workaholism is not just socially acceptable in medicine,” said Dr. Sukhera. “It’s baked into the system and built into the structures. The healthcare system has largely functioned on the emotional labor of health workers, whose tendency to show up and work harder can, at times, in certain organizations, be exploited.”
Dr. Griffiths agreed that with the limited amount of data available, work addiction does appear to exist at higher rates in medicine than in other fields. As early as the 1970s, medical literature describes work as a “socially acceptable” addiction among doctors. A 2014 study published in Occupational Medicine reported that of 445 physicians who took part in the research, nearly half exhibited some level of work addiction with 13% “highly work addicted.”
Of course, working hard or even meeting unreasonable demands from work is not the same as work addiction, as Dr. Griffiths clarified in a 2023 editorial in BMJ Quality & Safety. The difference, as with other behavioral addictions, is when people obsess about work and use it to cope with stress. It can be easier to stay distracted and busy to gain a sense of control rather than learning to deal with complex emotions.
A 2021 study that Dr. Sukhera conducted with resident physicians found that working harder was one of the main ways they dealt with stress during the COVID-19 pandemic. “This idea that we deal with the stress of being burnt out by doing more and more of what burns us out is fairly ubiquitous at all stages of medical professionals’ careers,” he said.
Financial incentives also can fuel work addiction, said Dr. Sukhera. In residency, there are some safeguards around overwork and duty hours. When you become an attending, those limits no longer exist. As a young physician, Dr. Sukhera had student debt to pay off and a family to support. When he found opportunities to earn more by working more, his answer was always “yes.”
Pressure to produce medical research also can pose issues. Some physicians can become addicted to publishing studies, fearing that they might lose their professional status or position if they stop. It’s a cycle that can force a doctor to not only work long hours doing their job but also practically take on a second one.
How Physicians Can Recognize Work Addiction in Themselves
Work addiction can look and feel different for every person, said Malissa Clark, PhD, associate professor at the University of Georgia and author of the recent book Never Not Working: Why the Always-On Culture Is Bad for Business—and How to Fix It.
Dr. Clark noted that people who are highly engaged in their work tend to be driven by intrinsic motivation: “You work because you love it.” With work addiction, “you work because you feel like you ought to be working all the time.”
Of course, it’s not always so cut and dried; you can experience both forms of motivation and not necessarily become addicted to work. But if you are solely driven by the feeling that you ought to be working all the time, that can be a red flag.
Dr. Griffiths said that while many people may have problematic work habits or work too much, true work addicts must meet six criteria that apply to all addictions:
1. Salience: Work is the single most important thing in your life, to the point of neglecting everything else. Even if you’re on vacation, your mind might be flooded with work thoughts.
2. Mood modification: You use work to modify your mood, either to get a “high” or to cope with stress.
3. Tolerance: Over time, you’ve gone from working 8 or 10 hours a day to 12 hours a day, to a point where you’re working all the time.
4. Withdrawal: On a physiological level, you will have symptoms such as anxiety, nausea, or headaches when unable to work.
5. Conflict: You feel conflicted with yourself (you know you’re working too much) or with others (partners, friends, and children) about work, but you can’t stop.
6. Relapse: If you manage to cut down your hours but can’t resist overworking 1 day, you wind up right back where you were.
When It’s Time to Address Work Addiction
The lack of a formal diagnosis for work addiction makes getting treatment difficult. But there are ways to seek help. Unlike the drug and alcohol literature, abstinence is not the goal. “The therapeutic goal is getting a behavior under control and looking for the triggers of why you’re compulsively working,” said Dr. Griffiths.
Practice self-compassion
Dr. Sukhera eventually realized that his work addiction stemmed from the fear of being somehow excluded or unworthy. He actively corrected much of this through self-compassion and self-kindness, which helped him set boundaries. “Self-compassion is the root of everything,” he said. “Reminding ourselves that we’re doing our best is an important ingredient in breaking the cycle.”
Slowly expose yourself to relaxation
Many workaholics find rest very difficult. “When I conducted interviews with people [who considered themselves workaholics], a very common thing I heard was, ‘I have a very hard time being idle,’ ” said Dr. Clark. If rest feels hard, Dr. Sukhera suggests practicing relaxation for 2 minutes to start. Even small periods of downtime can challenge the belief that you must be constantly productive.
Reframe your to-do list
For work addicts, to-do lists can seem like they must be finished, which prolongs work hours. Instead, use to-do lists to help prioritize what is urgent, identify what can wait, and delegate out tasks to others, Dr. Clark recommends.
Pick up a mastery experience
Research from professor Sabine Sonnentag, Dr. rer. nat., at the University of Mannheim, Mannheim, Germany, suggests that mastery experiences — leisure activities that require thought and focus like learning a new language or taking a woodworking class — can help you actively disengage from work.
Try cognitive behavioral therapy
Widely used for other forms of addiction, cognitive behavioral therapy centers around recognizing emotions, challenging thought patterns, and changing behaviors. However, Dr. Clark admits the research on its impact on work addiction, in particular, is “pretty nascent.”
Shift your mindset
It seems logical to think that detaching from your feelings will allow you to “do more,” but experts say that idea is both untrue and dangerous. “The safest hospitals are the hospitals where people are attuned to their humanness,” said Dr. Sukhera. “It’s normal to overwork in medicine, and if you’re challenging a norm, you really have to be thoughtful about how you frame that for yourself.”
Most importantly: Seek support
Today, there is increased awareness about work addiction and more resources for physicians who are struggling, including programs such as Workaholics Anonymous or Physicians Anonymous and workplace wellness initiatives. But try not to overwhelm yourself with choosing whom to talk to or what specific resource to utilize, Dr. Sukhera advised. “Just talk to someone about it. You don’t have to carry this on your own.”
A version of this article appeared on Medscape.com.
When child psychiatrist Javeed Sukhera, MD, PhD, was a few years into his career, he found himself doing it all. “I was in a leadership role academically at the medical school, I had a leadership role at the hospital, and I was seeing as many patients as I could. I could work all day every day.”
“It still wouldn’t have been enough,” he said.
Whenever there was a shift available, Dr. Sukhera would take it. His job was stressful, but as a new physician with a young family, he saw this obsession with work as necessary. “I began to cope with the stress from work by doing extra work and feeling like I needed to be everywhere. It was like I became a hamster on a spinning wheel. I was just running, running, running.”
Things shifted for Dr. Sukhera when he realized that while he was emotionally available for the children who were his patients, at home, his own children weren’t getting the best of him. “There was a specific moment when I thought my son was afraid of me,” he said. “I just stopped and realized that there was something happening that I needed to break. I needed to make a change.”
Dr. Sukhera, now chair of psychiatry at the Institute of Living and chief of the Department of Psychiatry at Hartford Hospital, Hartford, Connecticut, believes what he experienced was a steep fall into work addiction.
What Does Work Addiction Look Like for Doctors?
Behavioral addictions are fairly new in the addiction space. When gambling disorder, the first and only behavioral addiction in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, was added in 2013, it was seen as a “breakthrough addiction,” said Mark D. Griffiths, PhD, a leading behavioral addiction researcher and a distinguished professor at Nottingham Trent University.
Because there is not enough evidence yet to classify work addiction as a formal diagnosis, there is no clear consensus on how to define it. To further complicate things, the terms “workaholism” and “work addiction” can be used interchangeably, and some experts say the two are not the same, though they can overlap.
That said, a 2018 review of literature from several countries found that work addiction “fits very well into recently postulated criteria for conceptualization of a behavioral addiction.
“If you accept that gambling can be genuinely addictive, then there’s no reason to think that something like work, exercise, or video game playing couldn’t be an addiction as well,” said Dr. Griffiths.
“The neurobiology of addiction is that we get drawn to something that gives us a dopamine hit,” Dr. Sukhera added. “But to do that all day, every day, has consequences. It drains our emotional reserves, and it can greatly impact our relationships.”
On top of that, work addiction has been linked with poor sleep, poor cardiovascular health, high blood pressure, burnout, the development of autoimmune disorders, and other health issues.
Physicians are particularly susceptible. Doctors, after all, are expected to work long hours and put their patients’ needs first, even at the expense of their own health and well-being.
“Workaholism is not just socially acceptable in medicine,” said Dr. Sukhera. “It’s baked into the system and built into the structures. The healthcare system has largely functioned on the emotional labor of health workers, whose tendency to show up and work harder can, at times, in certain organizations, be exploited.”
Dr. Griffiths agreed that with the limited amount of data available, work addiction does appear to exist at higher rates in medicine than in other fields. As early as the 1970s, medical literature describes work as a “socially acceptable” addiction among doctors. A 2014 study published in Occupational Medicine reported that of 445 physicians who took part in the research, nearly half exhibited some level of work addiction with 13% “highly work addicted.”
Of course, working hard or even meeting unreasonable demands from work is not the same as work addiction, as Dr. Griffiths clarified in a 2023 editorial in BMJ Quality & Safety. The difference, as with other behavioral addictions, is when people obsess about work and use it to cope with stress. It can be easier to stay distracted and busy to gain a sense of control rather than learning to deal with complex emotions.
A 2021 study that Dr. Sukhera conducted with resident physicians found that working harder was one of the main ways they dealt with stress during the COVID-19 pandemic. “This idea that we deal with the stress of being burnt out by doing more and more of what burns us out is fairly ubiquitous at all stages of medical professionals’ careers,” he said.
Financial incentives also can fuel work addiction, said Dr. Sukhera. In residency, there are some safeguards around overwork and duty hours. When you become an attending, those limits no longer exist. As a young physician, Dr. Sukhera had student debt to pay off and a family to support. When he found opportunities to earn more by working more, his answer was always “yes.”
Pressure to produce medical research also can pose issues. Some physicians can become addicted to publishing studies, fearing that they might lose their professional status or position if they stop. It’s a cycle that can force a doctor to not only work long hours doing their job but also practically take on a second one.
How Physicians Can Recognize Work Addiction in Themselves
Work addiction can look and feel different for every person, said Malissa Clark, PhD, associate professor at the University of Georgia and author of the recent book Never Not Working: Why the Always-On Culture Is Bad for Business—and How to Fix It.
Dr. Clark noted that people who are highly engaged in their work tend to be driven by intrinsic motivation: “You work because you love it.” With work addiction, “you work because you feel like you ought to be working all the time.”
Of course, it’s not always so cut and dried; you can experience both forms of motivation and not necessarily become addicted to work. But if you are solely driven by the feeling that you ought to be working all the time, that can be a red flag.
Dr. Griffiths said that while many people may have problematic work habits or work too much, true work addicts must meet six criteria that apply to all addictions:
1. Salience: Work is the single most important thing in your life, to the point of neglecting everything else. Even if you’re on vacation, your mind might be flooded with work thoughts.
2. Mood modification: You use work to modify your mood, either to get a “high” or to cope with stress.
3. Tolerance: Over time, you’ve gone from working 8 or 10 hours a day to 12 hours a day, to a point where you’re working all the time.
4. Withdrawal: On a physiological level, you will have symptoms such as anxiety, nausea, or headaches when unable to work.
5. Conflict: You feel conflicted with yourself (you know you’re working too much) or with others (partners, friends, and children) about work, but you can’t stop.
6. Relapse: If you manage to cut down your hours but can’t resist overworking 1 day, you wind up right back where you were.
When It’s Time to Address Work Addiction
The lack of a formal diagnosis for work addiction makes getting treatment difficult. But there are ways to seek help. Unlike the drug and alcohol literature, abstinence is not the goal. “The therapeutic goal is getting a behavior under control and looking for the triggers of why you’re compulsively working,” said Dr. Griffiths.
Practice self-compassion
Dr. Sukhera eventually realized that his work addiction stemmed from the fear of being somehow excluded or unworthy. He actively corrected much of this through self-compassion and self-kindness, which helped him set boundaries. “Self-compassion is the root of everything,” he said. “Reminding ourselves that we’re doing our best is an important ingredient in breaking the cycle.”
Slowly expose yourself to relaxation
Many workaholics find rest very difficult. “When I conducted interviews with people [who considered themselves workaholics], a very common thing I heard was, ‘I have a very hard time being idle,’ ” said Dr. Clark. If rest feels hard, Dr. Sukhera suggests practicing relaxation for 2 minutes to start. Even small periods of downtime can challenge the belief that you must be constantly productive.
Reframe your to-do list
For work addicts, to-do lists can seem like they must be finished, which prolongs work hours. Instead, use to-do lists to help prioritize what is urgent, identify what can wait, and delegate out tasks to others, Dr. Clark recommends.
Pick up a mastery experience
Research from professor Sabine Sonnentag, Dr. rer. nat., at the University of Mannheim, Mannheim, Germany, suggests that mastery experiences — leisure activities that require thought and focus like learning a new language or taking a woodworking class — can help you actively disengage from work.
Try cognitive behavioral therapy
Widely used for other forms of addiction, cognitive behavioral therapy centers around recognizing emotions, challenging thought patterns, and changing behaviors. However, Dr. Clark admits the research on its impact on work addiction, in particular, is “pretty nascent.”
Shift your mindset
It seems logical to think that detaching from your feelings will allow you to “do more,” but experts say that idea is both untrue and dangerous. “The safest hospitals are the hospitals where people are attuned to their humanness,” said Dr. Sukhera. “It’s normal to overwork in medicine, and if you’re challenging a norm, you really have to be thoughtful about how you frame that for yourself.”
Most importantly: Seek support
Today, there is increased awareness about work addiction and more resources for physicians who are struggling, including programs such as Workaholics Anonymous or Physicians Anonymous and workplace wellness initiatives. But try not to overwhelm yourself with choosing whom to talk to or what specific resource to utilize, Dr. Sukhera advised. “Just talk to someone about it. You don’t have to carry this on your own.”
A version of this article appeared on Medscape.com.
When child psychiatrist Javeed Sukhera, MD, PhD, was a few years into his career, he found himself doing it all. “I was in a leadership role academically at the medical school, I had a leadership role at the hospital, and I was seeing as many patients as I could. I could work all day every day.”
“It still wouldn’t have been enough,” he said.
Whenever there was a shift available, Dr. Sukhera would take it. His job was stressful, but as a new physician with a young family, he saw this obsession with work as necessary. “I began to cope with the stress from work by doing extra work and feeling like I needed to be everywhere. It was like I became a hamster on a spinning wheel. I was just running, running, running.”
Things shifted for Dr. Sukhera when he realized that while he was emotionally available for the children who were his patients, at home, his own children weren’t getting the best of him. “There was a specific moment when I thought my son was afraid of me,” he said. “I just stopped and realized that there was something happening that I needed to break. I needed to make a change.”
Dr. Sukhera, now chair of psychiatry at the Institute of Living and chief of the Department of Psychiatry at Hartford Hospital, Hartford, Connecticut, believes what he experienced was a steep fall into work addiction.
What Does Work Addiction Look Like for Doctors?
Behavioral addictions are fairly new in the addiction space. When gambling disorder, the first and only behavioral addiction in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, was added in 2013, it was seen as a “breakthrough addiction,” said Mark D. Griffiths, PhD, a leading behavioral addiction researcher and a distinguished professor at Nottingham Trent University.
Because there is not enough evidence yet to classify work addiction as a formal diagnosis, there is no clear consensus on how to define it. To further complicate things, the terms “workaholism” and “work addiction” can be used interchangeably, and some experts say the two are not the same, though they can overlap.
That said, a 2018 review of literature from several countries found that work addiction “fits very well into recently postulated criteria for conceptualization of a behavioral addiction.
“If you accept that gambling can be genuinely addictive, then there’s no reason to think that something like work, exercise, or video game playing couldn’t be an addiction as well,” said Dr. Griffiths.
“The neurobiology of addiction is that we get drawn to something that gives us a dopamine hit,” Dr. Sukhera added. “But to do that all day, every day, has consequences. It drains our emotional reserves, and it can greatly impact our relationships.”
On top of that, work addiction has been linked with poor sleep, poor cardiovascular health, high blood pressure, burnout, the development of autoimmune disorders, and other health issues.
Physicians are particularly susceptible. Doctors, after all, are expected to work long hours and put their patients’ needs first, even at the expense of their own health and well-being.
“Workaholism is not just socially acceptable in medicine,” said Dr. Sukhera. “It’s baked into the system and built into the structures. The healthcare system has largely functioned on the emotional labor of health workers, whose tendency to show up and work harder can, at times, in certain organizations, be exploited.”
Dr. Griffiths agreed that with the limited amount of data available, work addiction does appear to exist at higher rates in medicine than in other fields. As early as the 1970s, medical literature describes work as a “socially acceptable” addiction among doctors. A 2014 study published in Occupational Medicine reported that of 445 physicians who took part in the research, nearly half exhibited some level of work addiction with 13% “highly work addicted.”
Of course, working hard or even meeting unreasonable demands from work is not the same as work addiction, as Dr. Griffiths clarified in a 2023 editorial in BMJ Quality & Safety. The difference, as with other behavioral addictions, is when people obsess about work and use it to cope with stress. It can be easier to stay distracted and busy to gain a sense of control rather than learning to deal with complex emotions.
A 2021 study that Dr. Sukhera conducted with resident physicians found that working harder was one of the main ways they dealt with stress during the COVID-19 pandemic. “This idea that we deal with the stress of being burnt out by doing more and more of what burns us out is fairly ubiquitous at all stages of medical professionals’ careers,” he said.
Financial incentives also can fuel work addiction, said Dr. Sukhera. In residency, there are some safeguards around overwork and duty hours. When you become an attending, those limits no longer exist. As a young physician, Dr. Sukhera had student debt to pay off and a family to support. When he found opportunities to earn more by working more, his answer was always “yes.”
Pressure to produce medical research also can pose issues. Some physicians can become addicted to publishing studies, fearing that they might lose their professional status or position if they stop. It’s a cycle that can force a doctor to not only work long hours doing their job but also practically take on a second one.
How Physicians Can Recognize Work Addiction in Themselves
Work addiction can look and feel different for every person, said Malissa Clark, PhD, associate professor at the University of Georgia and author of the recent book Never Not Working: Why the Always-On Culture Is Bad for Business—and How to Fix It.
Dr. Clark noted that people who are highly engaged in their work tend to be driven by intrinsic motivation: “You work because you love it.” With work addiction, “you work because you feel like you ought to be working all the time.”
Of course, it’s not always so cut and dried; you can experience both forms of motivation and not necessarily become addicted to work. But if you are solely driven by the feeling that you ought to be working all the time, that can be a red flag.
Dr. Griffiths said that while many people may have problematic work habits or work too much, true work addicts must meet six criteria that apply to all addictions:
1. Salience: Work is the single most important thing in your life, to the point of neglecting everything else. Even if you’re on vacation, your mind might be flooded with work thoughts.
2. Mood modification: You use work to modify your mood, either to get a “high” or to cope with stress.
3. Tolerance: Over time, you’ve gone from working 8 or 10 hours a day to 12 hours a day, to a point where you’re working all the time.
4. Withdrawal: On a physiological level, you will have symptoms such as anxiety, nausea, or headaches when unable to work.
5. Conflict: You feel conflicted with yourself (you know you’re working too much) or with others (partners, friends, and children) about work, but you can’t stop.
6. Relapse: If you manage to cut down your hours but can’t resist overworking 1 day, you wind up right back where you were.
When It’s Time to Address Work Addiction
The lack of a formal diagnosis for work addiction makes getting treatment difficult. But there are ways to seek help. Unlike the drug and alcohol literature, abstinence is not the goal. “The therapeutic goal is getting a behavior under control and looking for the triggers of why you’re compulsively working,” said Dr. Griffiths.
Practice self-compassion
Dr. Sukhera eventually realized that his work addiction stemmed from the fear of being somehow excluded or unworthy. He actively corrected much of this through self-compassion and self-kindness, which helped him set boundaries. “Self-compassion is the root of everything,” he said. “Reminding ourselves that we’re doing our best is an important ingredient in breaking the cycle.”
Slowly expose yourself to relaxation
Many workaholics find rest very difficult. “When I conducted interviews with people [who considered themselves workaholics], a very common thing I heard was, ‘I have a very hard time being idle,’ ” said Dr. Clark. If rest feels hard, Dr. Sukhera suggests practicing relaxation for 2 minutes to start. Even small periods of downtime can challenge the belief that you must be constantly productive.
Reframe your to-do list
For work addicts, to-do lists can seem like they must be finished, which prolongs work hours. Instead, use to-do lists to help prioritize what is urgent, identify what can wait, and delegate out tasks to others, Dr. Clark recommends.
Pick up a mastery experience
Research from professor Sabine Sonnentag, Dr. rer. nat., at the University of Mannheim, Mannheim, Germany, suggests that mastery experiences — leisure activities that require thought and focus like learning a new language or taking a woodworking class — can help you actively disengage from work.
Try cognitive behavioral therapy
Widely used for other forms of addiction, cognitive behavioral therapy centers around recognizing emotions, challenging thought patterns, and changing behaviors. However, Dr. Clark admits the research on its impact on work addiction, in particular, is “pretty nascent.”
Shift your mindset
It seems logical to think that detaching from your feelings will allow you to “do more,” but experts say that idea is both untrue and dangerous. “The safest hospitals are the hospitals where people are attuned to their humanness,” said Dr. Sukhera. “It’s normal to overwork in medicine, and if you’re challenging a norm, you really have to be thoughtful about how you frame that for yourself.”
Most importantly: Seek support
Today, there is increased awareness about work addiction and more resources for physicians who are struggling, including programs such as Workaholics Anonymous or Physicians Anonymous and workplace wellness initiatives. But try not to overwhelm yourself with choosing whom to talk to or what specific resource to utilize, Dr. Sukhera advised. “Just talk to someone about it. You don’t have to carry this on your own.”
A version of this article appeared on Medscape.com.
Few Cancer Survivors Meet ACS Nutrition, Exercise Guidelines
TOPLINE:
METHODOLOGY:
- The ACS has published nutrition and exercise guidelines for cancer survivors, which include recommendations to maintain a healthy weight and diet, cut out alcohol, and participate in regular physical activities. Engaging in these behaviors is associated with longer survival among cancer survivors, but whether survivors follow these nutrition and activity recommendations has not been systematically tracked.
- Researchers evaluated data on 10,020 individuals (mean age, 64.2 years) who had completed cancer treatment. Data came from the Behavioral Risk Factor Surveillance System telephone-based survey administered in 2017, 2019, and 2021, which represents 2.7 million cancer survivors.
- The researchers estimated survivors’ adherence to guidelines across four domains: Weight, physical activity, fruit and vegetable consumption, and alcohol intake. Factors associated with adherence were also evaluated.
- Overall, 9,121 survivors (91%) completed questionnaires for all four domains.
TAKEAWAY:
Only 4% of patients (365 of 9121) followed ACS guidelines in all four categories.
When assessing adherence to each category, the researchers found that 72% of cancer survivors reported engaging in recommended levels of physical activity, 68% maintained a nonobese weight, 50% said they did not consume alcohol, and 12% said they consumed recommended quantities of fruits and vegetables.
Compared with people in the general population, cancer survivors generally engaged in fewer healthy behaviors than those who had never been diagnosed with cancer.
The authors identified certain factors associated with greater guideline adherence, including female sex, older age, Black (vs White) race, and higher education level (college graduate).
IN PRACTICE:
This study highlights a potential “gap between published guidelines regarding behavioral modifications for cancer survivors and uptake of these behaviors,” the authors wrote, adding that “it is essential for oncologists and general internists to improve widespread and systematic counseling on these guidelines to improve uptake of healthy behaviors in this vulnerable patient population.”
SOURCE:
This work, led by Carter Baughman, MD, from the Division of Internal Medicine at Beth Israel Deaconess Medical Center, Boston, Massachusetts, was published online in JAMA Oncology.
LIMITATIONS:
The authors reported several study limitations, most notably that self-reported data may introduce biases.
DISCLOSURES:
The study funding source was not reported. One author received grants from the US Highbush Blueberry Council outside the submitted work. No other disclosures were reported.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- The ACS has published nutrition and exercise guidelines for cancer survivors, which include recommendations to maintain a healthy weight and diet, cut out alcohol, and participate in regular physical activities. Engaging in these behaviors is associated with longer survival among cancer survivors, but whether survivors follow these nutrition and activity recommendations has not been systematically tracked.
- Researchers evaluated data on 10,020 individuals (mean age, 64.2 years) who had completed cancer treatment. Data came from the Behavioral Risk Factor Surveillance System telephone-based survey administered in 2017, 2019, and 2021, which represents 2.7 million cancer survivors.
- The researchers estimated survivors’ adherence to guidelines across four domains: Weight, physical activity, fruit and vegetable consumption, and alcohol intake. Factors associated with adherence were also evaluated.
- Overall, 9,121 survivors (91%) completed questionnaires for all four domains.
TAKEAWAY:
Only 4% of patients (365 of 9121) followed ACS guidelines in all four categories.
When assessing adherence to each category, the researchers found that 72% of cancer survivors reported engaging in recommended levels of physical activity, 68% maintained a nonobese weight, 50% said they did not consume alcohol, and 12% said they consumed recommended quantities of fruits and vegetables.
Compared with people in the general population, cancer survivors generally engaged in fewer healthy behaviors than those who had never been diagnosed with cancer.
The authors identified certain factors associated with greater guideline adherence, including female sex, older age, Black (vs White) race, and higher education level (college graduate).
IN PRACTICE:
This study highlights a potential “gap between published guidelines regarding behavioral modifications for cancer survivors and uptake of these behaviors,” the authors wrote, adding that “it is essential for oncologists and general internists to improve widespread and systematic counseling on these guidelines to improve uptake of healthy behaviors in this vulnerable patient population.”
SOURCE:
This work, led by Carter Baughman, MD, from the Division of Internal Medicine at Beth Israel Deaconess Medical Center, Boston, Massachusetts, was published online in JAMA Oncology.
LIMITATIONS:
The authors reported several study limitations, most notably that self-reported data may introduce biases.
DISCLOSURES:
The study funding source was not reported. One author received grants from the US Highbush Blueberry Council outside the submitted work. No other disclosures were reported.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- The ACS has published nutrition and exercise guidelines for cancer survivors, which include recommendations to maintain a healthy weight and diet, cut out alcohol, and participate in regular physical activities. Engaging in these behaviors is associated with longer survival among cancer survivors, but whether survivors follow these nutrition and activity recommendations has not been systematically tracked.
- Researchers evaluated data on 10,020 individuals (mean age, 64.2 years) who had completed cancer treatment. Data came from the Behavioral Risk Factor Surveillance System telephone-based survey administered in 2017, 2019, and 2021, which represents 2.7 million cancer survivors.
- The researchers estimated survivors’ adherence to guidelines across four domains: Weight, physical activity, fruit and vegetable consumption, and alcohol intake. Factors associated with adherence were also evaluated.
- Overall, 9,121 survivors (91%) completed questionnaires for all four domains.
TAKEAWAY:
Only 4% of patients (365 of 9121) followed ACS guidelines in all four categories.
When assessing adherence to each category, the researchers found that 72% of cancer survivors reported engaging in recommended levels of physical activity, 68% maintained a nonobese weight, 50% said they did not consume alcohol, and 12% said they consumed recommended quantities of fruits and vegetables.
Compared with people in the general population, cancer survivors generally engaged in fewer healthy behaviors than those who had never been diagnosed with cancer.
The authors identified certain factors associated with greater guideline adherence, including female sex, older age, Black (vs White) race, and higher education level (college graduate).
IN PRACTICE:
This study highlights a potential “gap between published guidelines regarding behavioral modifications for cancer survivors and uptake of these behaviors,” the authors wrote, adding that “it is essential for oncologists and general internists to improve widespread and systematic counseling on these guidelines to improve uptake of healthy behaviors in this vulnerable patient population.”
SOURCE:
This work, led by Carter Baughman, MD, from the Division of Internal Medicine at Beth Israel Deaconess Medical Center, Boston, Massachusetts, was published online in JAMA Oncology.
LIMITATIONS:
The authors reported several study limitations, most notably that self-reported data may introduce biases.
DISCLOSURES:
The study funding source was not reported. One author received grants from the US Highbush Blueberry Council outside the submitted work. No other disclosures were reported.
A version of this article appeared on Medscape.com.
FDA Approves Second Gene Therapy for Hemophilia B
Patients are eligible for a one-time infusion of Pfizer’s gene therapy if they are currently using clotting factor IX prophylaxis therapy; have current or historical life-threatening hemorrhages; or have repeated, serious spontaneous bleeding episodes.
Beqvez is the second gene therapy the agency has approved for hemophilia B, a deficiency in clotting factor IX because of a faulty gene that occurs mostly in males. The FDA approved the first gene therapy, etranacogene dezaparvovec (Hemgenix), in November 2022.
Both therapies deliver a functional copy of the factor IX gene to liver cells via a viral vector.
Pfizer said the list price of Beqvez will be $3.5 million — the same price as Hemgenix. The argument for this hefty price tag is that these gene therapies offer the possibility of a cure whereas ongoing factor IX infusions can cost more than $20 million over a patient’s lifetime. Uptake of Hemgenix, however, has been slow, given the cost and concerns about the therapy’s durability and safety.
Beqvez was approved on the basis of the phase 3 BENEGENE-2 trial in 45 men with moderate to severe hemophilia B. These men had been on factor IX prophylaxis for at least 6 months and had tested negative for antibodies against the viral delivery vector.
The annualized bleeding rate fell from a mean of 4.5 events during the pretreatment period of at least 6 months to a mean of 2.5 events between week 12 and data cutoff (median, 1.8 years of follow-up), according to Pfizer’s press release. Overall, bleeding events were eliminated in 60% of patients who received the one-time infusion vs 29% of patients on factor IX prophylaxis therapy.
Overall, Pfizer reported that the gene therapy was “generally well-tolerated,” with an increase in transaminases reported as the most common adverse event. No deaths, serious infusion reactions, thrombotic events, or development of factor IX antibodies occurred.
Pfizer has said it will continue to monitor patients to assess the therapy’s long-term durability and safety over a 15-year period.
A version of this article appeared on Medscape.com.
Patients are eligible for a one-time infusion of Pfizer’s gene therapy if they are currently using clotting factor IX prophylaxis therapy; have current or historical life-threatening hemorrhages; or have repeated, serious spontaneous bleeding episodes.
Beqvez is the second gene therapy the agency has approved for hemophilia B, a deficiency in clotting factor IX because of a faulty gene that occurs mostly in males. The FDA approved the first gene therapy, etranacogene dezaparvovec (Hemgenix), in November 2022.
Both therapies deliver a functional copy of the factor IX gene to liver cells via a viral vector.
Pfizer said the list price of Beqvez will be $3.5 million — the same price as Hemgenix. The argument for this hefty price tag is that these gene therapies offer the possibility of a cure whereas ongoing factor IX infusions can cost more than $20 million over a patient’s lifetime. Uptake of Hemgenix, however, has been slow, given the cost and concerns about the therapy’s durability and safety.
Beqvez was approved on the basis of the phase 3 BENEGENE-2 trial in 45 men with moderate to severe hemophilia B. These men had been on factor IX prophylaxis for at least 6 months and had tested negative for antibodies against the viral delivery vector.
The annualized bleeding rate fell from a mean of 4.5 events during the pretreatment period of at least 6 months to a mean of 2.5 events between week 12 and data cutoff (median, 1.8 years of follow-up), according to Pfizer’s press release. Overall, bleeding events were eliminated in 60% of patients who received the one-time infusion vs 29% of patients on factor IX prophylaxis therapy.
Overall, Pfizer reported that the gene therapy was “generally well-tolerated,” with an increase in transaminases reported as the most common adverse event. No deaths, serious infusion reactions, thrombotic events, or development of factor IX antibodies occurred.
Pfizer has said it will continue to monitor patients to assess the therapy’s long-term durability and safety over a 15-year period.
A version of this article appeared on Medscape.com.
Patients are eligible for a one-time infusion of Pfizer’s gene therapy if they are currently using clotting factor IX prophylaxis therapy; have current or historical life-threatening hemorrhages; or have repeated, serious spontaneous bleeding episodes.
Beqvez is the second gene therapy the agency has approved for hemophilia B, a deficiency in clotting factor IX because of a faulty gene that occurs mostly in males. The FDA approved the first gene therapy, etranacogene dezaparvovec (Hemgenix), in November 2022.
Both therapies deliver a functional copy of the factor IX gene to liver cells via a viral vector.
Pfizer said the list price of Beqvez will be $3.5 million — the same price as Hemgenix. The argument for this hefty price tag is that these gene therapies offer the possibility of a cure whereas ongoing factor IX infusions can cost more than $20 million over a patient’s lifetime. Uptake of Hemgenix, however, has been slow, given the cost and concerns about the therapy’s durability and safety.
Beqvez was approved on the basis of the phase 3 BENEGENE-2 trial in 45 men with moderate to severe hemophilia B. These men had been on factor IX prophylaxis for at least 6 months and had tested negative for antibodies against the viral delivery vector.
The annualized bleeding rate fell from a mean of 4.5 events during the pretreatment period of at least 6 months to a mean of 2.5 events between week 12 and data cutoff (median, 1.8 years of follow-up), according to Pfizer’s press release. Overall, bleeding events were eliminated in 60% of patients who received the one-time infusion vs 29% of patients on factor IX prophylaxis therapy.
Overall, Pfizer reported that the gene therapy was “generally well-tolerated,” with an increase in transaminases reported as the most common adverse event. No deaths, serious infusion reactions, thrombotic events, or development of factor IX antibodies occurred.
Pfizer has said it will continue to monitor patients to assess the therapy’s long-term durability and safety over a 15-year period.
A version of this article appeared on Medscape.com.
Oregon Physician Assistants Get Name Change
On April 4, Oregon’s Governor Tina Kotek signed a bill into law that officially changed the title of “physician assistants” to “physician associates” in the state.
In the Medscape Physician Assistant Career Satisfaction Report 2023, a diverse range of opinions on the title switch was reflected. Only 40% of PAs favored the name change at the time, 45% neither opposed nor favored it, and 15% opposed the name change, reflecting the complexity of the issue.
According to the AAPA, the change came about to better reflect the work PAs do in not just “assisting” physicians but in working independently with patients. Some also felt that the word “assistant” implies dependence. However, despite associate’s more accurate reflection of the job, PAs mostly remain split on whether they want the new moniker.
Many say that the name change will be confusing for the public and their patients, while others say that physician assistant was already not well understood, as patients often thought of the profession as a doctor’s helper or an assistant, like a medical assistant.
Yet many long-time PAs say that they prefer the title they’ve always had and that explaining to patients the new associate title will be equally confusing. Some mentioned patients may think they’re a business associate of the physician.
Oregon PAs won’t immediately switch to the new name. The new law takes effect on June 6, 2024. The Oregon Medical Board will establish regulations and guidance before PAs adopt the new name in their practices.
The law only changes the name of PAs in Oregon, not in other states. In fact, prematurely using the title of physician associate could subject a PA to regulatory challenges or disciplinary actions.
A version of this article appeared on Medscape.com.
On April 4, Oregon’s Governor Tina Kotek signed a bill into law that officially changed the title of “physician assistants” to “physician associates” in the state.
In the Medscape Physician Assistant Career Satisfaction Report 2023, a diverse range of opinions on the title switch was reflected. Only 40% of PAs favored the name change at the time, 45% neither opposed nor favored it, and 15% opposed the name change, reflecting the complexity of the issue.
According to the AAPA, the change came about to better reflect the work PAs do in not just “assisting” physicians but in working independently with patients. Some also felt that the word “assistant” implies dependence. However, despite associate’s more accurate reflection of the job, PAs mostly remain split on whether they want the new moniker.
Many say that the name change will be confusing for the public and their patients, while others say that physician assistant was already not well understood, as patients often thought of the profession as a doctor’s helper or an assistant, like a medical assistant.
Yet many long-time PAs say that they prefer the title they’ve always had and that explaining to patients the new associate title will be equally confusing. Some mentioned patients may think they’re a business associate of the physician.
Oregon PAs won’t immediately switch to the new name. The new law takes effect on June 6, 2024. The Oregon Medical Board will establish regulations and guidance before PAs adopt the new name in their practices.
The law only changes the name of PAs in Oregon, not in other states. In fact, prematurely using the title of physician associate could subject a PA to regulatory challenges or disciplinary actions.
A version of this article appeared on Medscape.com.
On April 4, Oregon’s Governor Tina Kotek signed a bill into law that officially changed the title of “physician assistants” to “physician associates” in the state.
In the Medscape Physician Assistant Career Satisfaction Report 2023, a diverse range of opinions on the title switch was reflected. Only 40% of PAs favored the name change at the time, 45% neither opposed nor favored it, and 15% opposed the name change, reflecting the complexity of the issue.
According to the AAPA, the change came about to better reflect the work PAs do in not just “assisting” physicians but in working independently with patients. Some also felt that the word “assistant” implies dependence. However, despite associate’s more accurate reflection of the job, PAs mostly remain split on whether they want the new moniker.
Many say that the name change will be confusing for the public and their patients, while others say that physician assistant was already not well understood, as patients often thought of the profession as a doctor’s helper or an assistant, like a medical assistant.
Yet many long-time PAs say that they prefer the title they’ve always had and that explaining to patients the new associate title will be equally confusing. Some mentioned patients may think they’re a business associate of the physician.
Oregon PAs won’t immediately switch to the new name. The new law takes effect on June 6, 2024. The Oregon Medical Board will establish regulations and guidance before PAs adopt the new name in their practices.
The law only changes the name of PAs in Oregon, not in other states. In fact, prematurely using the title of physician associate could subject a PA to regulatory challenges or disciplinary actions.
A version of this article appeared on Medscape.com.
How These Young MDs Impressed the Hell Out of Their Bosses
Safe to say that anyone undertaking the physician journey does so with intense motivation and book smarts. Still, it can be incredibly hard to stand out. Everyone’s a go-getter, but what’s the X factor?
Here’s what they said ...
Lesson #1: Never Be Scared to Ask
Brien Barnewolt, MD, chairman and chief of the Department of Emergency Medicine at Tufts Medical Center, was very much surprised when a resident named Scott G. Weiner did something unexpected: Go after a job in the fall of his junior year residency instead of following the typical senior year trajectory.
“It’s very unusual for a trainee to apply for a job virtually a year ahead of schedule. But he knew what he wanted,” said Dr. Barnewolt. “I’d never had anybody come to me in that same scenario, and I’ve been doing this a long time.”
Under normal circumstances it would’ve been easy for Dr. Barnewolt to say no. But the unexpected request made him and his colleagues take a closer look, and they were impressed with Dr. Weiner’s skills. That, paired with his ambition and demeanor, compelled them to offer him an early job. But there’s more.
As the next year approached, Dr. Weiner explained he had an opportunity to work in emergency medicine in Tuscany and asked if he could take a 1-year delayed start for the position he applied a year early for.
The department held his position, and upon his return, Dr. Weiner made a lasting impact at Tufts before eventually moving on. “He outgrew us, which is nice to see,” Dr. Barnewolt said. (Dr. Weiner is currently McGraw Distinguished Chair in Emergency Medicine at Brigham and Women’s Hospital and associate professor at Harvard Medical School.)
Bottom line: Why did Dr. Barnewolt and his colleagues do so much to accommodate a young candidate? Yes, Dr. Weiner was talented, but he was also up-front about his ambitions from the get-go. Dr. Barnewolt said that kind of initiative can only be looked at positively.
“My advice would be, if you see an opportunity or a potential place where you might want to work, put out those feelers, start those conversations,” he said. “It’s not too early, especially in certain specialties, where the job market is very tight. Then, when circumstances change, be open about it and have that conversation. The worst that somebody can say is no, so it never hurts to be honest and open about where you want to go and what you want to be.”
Lesson #2: Chase Your Passion ‘Relentlessly’
Vance G. Fowler, MD, MHS, an infectious disease specialist at Duke University School of Medicine, runs a laboratory that researches methicillin-resistant Staphylococcus aureus (MRSA). Over the years, he’s mentored many doctors but understands the ambitions of young trainees don’t always align with the little free time that they have. “Many of them drop away when you give them a [side] project,” he said.
So when Tori Kinamon asked him to work on an MRSA project — in her first year — he gave her one that focused on researching vertebral osteomyelitis, a bone infection that can coincide with S aureus. What Dr. Fowler didn’t know: Kinamon (now MD) had been a competitive gymnast at Brown and battled her own life-threatening infection with MRSA.
“To my absolute astonishment, not only did she stick to it, but she was able to compile a presentation on the science and gave an oral presentation within a year of walking in the door,” said Dr. Fowler.
She went on to lead an initiative between the National Institutes of Health and US Food and Drug Administration to create endpoints for clinical drug trials, all of which occurred before starting her residency, which she’s about to embark upon.
Dr. Kinamon’s a good example, he said, of what happens when you add genuine passion to book smarts. Those who do always stand out because you can’t fake that. “Find your passion, and then chase it down relentlessly,” he said. “Once you’ve found your passion, things get easy because it stops being work and it starts being something else.”
If you haven’t identified a focus area, Dr. Fowler said to “be agnostic and observant. Keep your eyes open and your options open because you may surprise yourself. It may turn out that you end up liking something a whole lot more than you thought you did.”
Lesson #3: When You Say You’ve Always Wanted to Do Something, Do Something
As the chief of pulmonary and critical care medicine at the Northwestern Medicine Canning Thoracic Institute, Scott Budinger, MD, often hears lip service from doctors who want to put their skills to use in their local communities. One of his students actually did it.
Justin Fiala, MD, a pulmonary, critical care, and sleep specialist at Northwestern Medicine, joined Northwestern as a pulmonary fellow with a big interest in addressing health equity issues.
Dr. Fiala began volunteering with CommunityHealth during his fellowship and saw that many patients of the free Chicago-area clinic needed help with sleep disorders. He launched the organization’s first sleep clinic and its Patient-Centered Apnea Protocols Initiative.
“He developed a plan with some of the partners of the sleep apnea equipment to do home sleep testing for these patients that’s free of cost,” said Dr. Budinger.
Dr. Fiala goes in on Saturdays and runs a free clinic conducting sleep studies for patients and outfits them with devices that they need to improve their conditions, said Dr. Budinger.
“And these patients are the severest of the severe patients,” he said. “These are people that have severe sleep apnea that are driving around the roads, oftentimes don’t have insurance because they’re also precluded from having auto insurance. So, this is really something that not just benefits these patients but benefits our whole community.”
The fact that Dr. Fiala followed through on something that all doctors aspire to do — and in the middle of a very busy training program — is something that Dr. Budinger said makes him stand out in a big way.
“If you talk to any of our trainees or young faculty, everybody’s interested in addressing the issue of health disparities,” said Dr. Budinger. “Justin looked at that and said, ‘Well, you know, I’m not interested in talking about it. What can I do about this problem? And how can I actually get boots on the ground and help?’ That requires a big activation energy that many people don’t have.”
Lesson #4: Be a People-Person and a Patient-Person
When hiring employees at American Family Care in Portland, Oregon, Andrew Miller, MD, director of provider training, is always on the lookout for young MDs with emotional intelligence and a good bedside manner. He has been recently blown away, however, by a young physician’s assistant named Joseph Van Bindsbergen, PA-C, who was described as “all-around wonderful” during his reference check.
“Having less than 6 months of experience out of school, he is our highest ranked provider, whether it’s a nurse practitioner, PA, or doctor, in terms of patient satisfaction,” said Dr. Miller. The young PA has an “unprecedented perfect score” on his NPS rating.
Why? Patients said they’ve never felt as heard as they felt with Van Bindsbergen.
“That’s the thing I think that the up-and-coming providers should be focusing on is making your patients feel heard,” explained Dr. Miller. Van Bindsbergen is great at building rapport with a patient, whether they are 6 or 96. “He doesn’t just ask about sore throat symptoms. He asks, ‘what is the impact on your life of the sore throat? How does it affect your family or your work? What do you think this could be besides just strep? What are your concerns?’ ”
Dr. Miller said the magic of Van Bindsbergen is that he has an innate ability to look at patients “not just as a diagnosis but as a person, which they love.”
Lesson #5: Remember to Make That Difference With Each Patient
Doctors are used to swooping in and seeing a patient, ordering further testing if needed, and then moving on to the next patient. But one young intern at the start of his medical career broke this mold by giving a very anxious patient some much-needed support.
“There was a resident who was working overnight, and this poor young woman came in who had a new diagnosis of an advanced illness and a lot of anxiety around her condition, the newness of it, and the impact this is going to have on her family and her life,” said Elizabeth Horn Prsic, MD, assistant professor at Yale School of Medicine and firm chief for medical oncology and the director of Adult Inpatient Palliative Care.
Dr. Prsic found out the next morning that this trainee accompanied the patient to the MRI and held her hand as much as he was allowed to throughout the entire experience. “I was like, ‘wait you went down with her to radiology?’ And he’s like, ‘Yes, I was there the whole time,’ ” she recalled.
This gesture not only helped the patient feel calmer after receiving a potentially life-altering diagnosis but also helped ensure the test results were as clear as possible.
“If the study is not done well and a patient is moving or uncomfortable, it has to be stopped early or paused,” said Dr. Prsic. “Then the study is not very useful. In situations like these, medical decisions may be made based on imperfect data. The fact that we had this full complete good quality scan helped us get the care that she needed in a much timelier manner to help her and to move along the care that she that was medically appropriate for her.”
Dr. Prsic got emotional reflecting on the experience. Working at Yale, she saw a ton of intelligent doctors come through the ranks. But this gesture, she said, should serve as a reminder that “you don’t need to be the smartest person in the room to just be there for a patient. It was pure empathic presence and human connection. It gave me hope in the next generation of physicians.”
A version of this article appeared on Medscape.com.
Safe to say that anyone undertaking the physician journey does so with intense motivation and book smarts. Still, it can be incredibly hard to stand out. Everyone’s a go-getter, but what’s the X factor?
Here’s what they said ...
Lesson #1: Never Be Scared to Ask
Brien Barnewolt, MD, chairman and chief of the Department of Emergency Medicine at Tufts Medical Center, was very much surprised when a resident named Scott G. Weiner did something unexpected: Go after a job in the fall of his junior year residency instead of following the typical senior year trajectory.
“It’s very unusual for a trainee to apply for a job virtually a year ahead of schedule. But he knew what he wanted,” said Dr. Barnewolt. “I’d never had anybody come to me in that same scenario, and I’ve been doing this a long time.”
Under normal circumstances it would’ve been easy for Dr. Barnewolt to say no. But the unexpected request made him and his colleagues take a closer look, and they were impressed with Dr. Weiner’s skills. That, paired with his ambition and demeanor, compelled them to offer him an early job. But there’s more.
As the next year approached, Dr. Weiner explained he had an opportunity to work in emergency medicine in Tuscany and asked if he could take a 1-year delayed start for the position he applied a year early for.
The department held his position, and upon his return, Dr. Weiner made a lasting impact at Tufts before eventually moving on. “He outgrew us, which is nice to see,” Dr. Barnewolt said. (Dr. Weiner is currently McGraw Distinguished Chair in Emergency Medicine at Brigham and Women’s Hospital and associate professor at Harvard Medical School.)
Bottom line: Why did Dr. Barnewolt and his colleagues do so much to accommodate a young candidate? Yes, Dr. Weiner was talented, but he was also up-front about his ambitions from the get-go. Dr. Barnewolt said that kind of initiative can only be looked at positively.
“My advice would be, if you see an opportunity or a potential place where you might want to work, put out those feelers, start those conversations,” he said. “It’s not too early, especially in certain specialties, where the job market is very tight. Then, when circumstances change, be open about it and have that conversation. The worst that somebody can say is no, so it never hurts to be honest and open about where you want to go and what you want to be.”
Lesson #2: Chase Your Passion ‘Relentlessly’
Vance G. Fowler, MD, MHS, an infectious disease specialist at Duke University School of Medicine, runs a laboratory that researches methicillin-resistant Staphylococcus aureus (MRSA). Over the years, he’s mentored many doctors but understands the ambitions of young trainees don’t always align with the little free time that they have. “Many of them drop away when you give them a [side] project,” he said.
So when Tori Kinamon asked him to work on an MRSA project — in her first year — he gave her one that focused on researching vertebral osteomyelitis, a bone infection that can coincide with S aureus. What Dr. Fowler didn’t know: Kinamon (now MD) had been a competitive gymnast at Brown and battled her own life-threatening infection with MRSA.
“To my absolute astonishment, not only did she stick to it, but she was able to compile a presentation on the science and gave an oral presentation within a year of walking in the door,” said Dr. Fowler.
She went on to lead an initiative between the National Institutes of Health and US Food and Drug Administration to create endpoints for clinical drug trials, all of which occurred before starting her residency, which she’s about to embark upon.
Dr. Kinamon’s a good example, he said, of what happens when you add genuine passion to book smarts. Those who do always stand out because you can’t fake that. “Find your passion, and then chase it down relentlessly,” he said. “Once you’ve found your passion, things get easy because it stops being work and it starts being something else.”
If you haven’t identified a focus area, Dr. Fowler said to “be agnostic and observant. Keep your eyes open and your options open because you may surprise yourself. It may turn out that you end up liking something a whole lot more than you thought you did.”
Lesson #3: When You Say You’ve Always Wanted to Do Something, Do Something
As the chief of pulmonary and critical care medicine at the Northwestern Medicine Canning Thoracic Institute, Scott Budinger, MD, often hears lip service from doctors who want to put their skills to use in their local communities. One of his students actually did it.
Justin Fiala, MD, a pulmonary, critical care, and sleep specialist at Northwestern Medicine, joined Northwestern as a pulmonary fellow with a big interest in addressing health equity issues.
Dr. Fiala began volunteering with CommunityHealth during his fellowship and saw that many patients of the free Chicago-area clinic needed help with sleep disorders. He launched the organization’s first sleep clinic and its Patient-Centered Apnea Protocols Initiative.
“He developed a plan with some of the partners of the sleep apnea equipment to do home sleep testing for these patients that’s free of cost,” said Dr. Budinger.
Dr. Fiala goes in on Saturdays and runs a free clinic conducting sleep studies for patients and outfits them with devices that they need to improve their conditions, said Dr. Budinger.
“And these patients are the severest of the severe patients,” he said. “These are people that have severe sleep apnea that are driving around the roads, oftentimes don’t have insurance because they’re also precluded from having auto insurance. So, this is really something that not just benefits these patients but benefits our whole community.”
The fact that Dr. Fiala followed through on something that all doctors aspire to do — and in the middle of a very busy training program — is something that Dr. Budinger said makes him stand out in a big way.
“If you talk to any of our trainees or young faculty, everybody’s interested in addressing the issue of health disparities,” said Dr. Budinger. “Justin looked at that and said, ‘Well, you know, I’m not interested in talking about it. What can I do about this problem? And how can I actually get boots on the ground and help?’ That requires a big activation energy that many people don’t have.”
Lesson #4: Be a People-Person and a Patient-Person
When hiring employees at American Family Care in Portland, Oregon, Andrew Miller, MD, director of provider training, is always on the lookout for young MDs with emotional intelligence and a good bedside manner. He has been recently blown away, however, by a young physician’s assistant named Joseph Van Bindsbergen, PA-C, who was described as “all-around wonderful” during his reference check.
“Having less than 6 months of experience out of school, he is our highest ranked provider, whether it’s a nurse practitioner, PA, or doctor, in terms of patient satisfaction,” said Dr. Miller. The young PA has an “unprecedented perfect score” on his NPS rating.
Why? Patients said they’ve never felt as heard as they felt with Van Bindsbergen.
“That’s the thing I think that the up-and-coming providers should be focusing on is making your patients feel heard,” explained Dr. Miller. Van Bindsbergen is great at building rapport with a patient, whether they are 6 or 96. “He doesn’t just ask about sore throat symptoms. He asks, ‘what is the impact on your life of the sore throat? How does it affect your family or your work? What do you think this could be besides just strep? What are your concerns?’ ”
Dr. Miller said the magic of Van Bindsbergen is that he has an innate ability to look at patients “not just as a diagnosis but as a person, which they love.”
Lesson #5: Remember to Make That Difference With Each Patient
Doctors are used to swooping in and seeing a patient, ordering further testing if needed, and then moving on to the next patient. But one young intern at the start of his medical career broke this mold by giving a very anxious patient some much-needed support.
“There was a resident who was working overnight, and this poor young woman came in who had a new diagnosis of an advanced illness and a lot of anxiety around her condition, the newness of it, and the impact this is going to have on her family and her life,” said Elizabeth Horn Prsic, MD, assistant professor at Yale School of Medicine and firm chief for medical oncology and the director of Adult Inpatient Palliative Care.
Dr. Prsic found out the next morning that this trainee accompanied the patient to the MRI and held her hand as much as he was allowed to throughout the entire experience. “I was like, ‘wait you went down with her to radiology?’ And he’s like, ‘Yes, I was there the whole time,’ ” she recalled.
This gesture not only helped the patient feel calmer after receiving a potentially life-altering diagnosis but also helped ensure the test results were as clear as possible.
“If the study is not done well and a patient is moving or uncomfortable, it has to be stopped early or paused,” said Dr. Prsic. “Then the study is not very useful. In situations like these, medical decisions may be made based on imperfect data. The fact that we had this full complete good quality scan helped us get the care that she needed in a much timelier manner to help her and to move along the care that she that was medically appropriate for her.”
Dr. Prsic got emotional reflecting on the experience. Working at Yale, she saw a ton of intelligent doctors come through the ranks. But this gesture, she said, should serve as a reminder that “you don’t need to be the smartest person in the room to just be there for a patient. It was pure empathic presence and human connection. It gave me hope in the next generation of physicians.”
A version of this article appeared on Medscape.com.
Safe to say that anyone undertaking the physician journey does so with intense motivation and book smarts. Still, it can be incredibly hard to stand out. Everyone’s a go-getter, but what’s the X factor?
Here’s what they said ...
Lesson #1: Never Be Scared to Ask
Brien Barnewolt, MD, chairman and chief of the Department of Emergency Medicine at Tufts Medical Center, was very much surprised when a resident named Scott G. Weiner did something unexpected: Go after a job in the fall of his junior year residency instead of following the typical senior year trajectory.
“It’s very unusual for a trainee to apply for a job virtually a year ahead of schedule. But he knew what he wanted,” said Dr. Barnewolt. “I’d never had anybody come to me in that same scenario, and I’ve been doing this a long time.”
Under normal circumstances it would’ve been easy for Dr. Barnewolt to say no. But the unexpected request made him and his colleagues take a closer look, and they were impressed with Dr. Weiner’s skills. That, paired with his ambition and demeanor, compelled them to offer him an early job. But there’s more.
As the next year approached, Dr. Weiner explained he had an opportunity to work in emergency medicine in Tuscany and asked if he could take a 1-year delayed start for the position he applied a year early for.
The department held his position, and upon his return, Dr. Weiner made a lasting impact at Tufts before eventually moving on. “He outgrew us, which is nice to see,” Dr. Barnewolt said. (Dr. Weiner is currently McGraw Distinguished Chair in Emergency Medicine at Brigham and Women’s Hospital and associate professor at Harvard Medical School.)
Bottom line: Why did Dr. Barnewolt and his colleagues do so much to accommodate a young candidate? Yes, Dr. Weiner was talented, but he was also up-front about his ambitions from the get-go. Dr. Barnewolt said that kind of initiative can only be looked at positively.
“My advice would be, if you see an opportunity or a potential place where you might want to work, put out those feelers, start those conversations,” he said. “It’s not too early, especially in certain specialties, where the job market is very tight. Then, when circumstances change, be open about it and have that conversation. The worst that somebody can say is no, so it never hurts to be honest and open about where you want to go and what you want to be.”
Lesson #2: Chase Your Passion ‘Relentlessly’
Vance G. Fowler, MD, MHS, an infectious disease specialist at Duke University School of Medicine, runs a laboratory that researches methicillin-resistant Staphylococcus aureus (MRSA). Over the years, he’s mentored many doctors but understands the ambitions of young trainees don’t always align with the little free time that they have. “Many of them drop away when you give them a [side] project,” he said.
So when Tori Kinamon asked him to work on an MRSA project — in her first year — he gave her one that focused on researching vertebral osteomyelitis, a bone infection that can coincide with S aureus. What Dr. Fowler didn’t know: Kinamon (now MD) had been a competitive gymnast at Brown and battled her own life-threatening infection with MRSA.
“To my absolute astonishment, not only did she stick to it, but she was able to compile a presentation on the science and gave an oral presentation within a year of walking in the door,” said Dr. Fowler.
She went on to lead an initiative between the National Institutes of Health and US Food and Drug Administration to create endpoints for clinical drug trials, all of which occurred before starting her residency, which she’s about to embark upon.
Dr. Kinamon’s a good example, he said, of what happens when you add genuine passion to book smarts. Those who do always stand out because you can’t fake that. “Find your passion, and then chase it down relentlessly,” he said. “Once you’ve found your passion, things get easy because it stops being work and it starts being something else.”
If you haven’t identified a focus area, Dr. Fowler said to “be agnostic and observant. Keep your eyes open and your options open because you may surprise yourself. It may turn out that you end up liking something a whole lot more than you thought you did.”
Lesson #3: When You Say You’ve Always Wanted to Do Something, Do Something
As the chief of pulmonary and critical care medicine at the Northwestern Medicine Canning Thoracic Institute, Scott Budinger, MD, often hears lip service from doctors who want to put their skills to use in their local communities. One of his students actually did it.
Justin Fiala, MD, a pulmonary, critical care, and sleep specialist at Northwestern Medicine, joined Northwestern as a pulmonary fellow with a big interest in addressing health equity issues.
Dr. Fiala began volunteering with CommunityHealth during his fellowship and saw that many patients of the free Chicago-area clinic needed help with sleep disorders. He launched the organization’s first sleep clinic and its Patient-Centered Apnea Protocols Initiative.
“He developed a plan with some of the partners of the sleep apnea equipment to do home sleep testing for these patients that’s free of cost,” said Dr. Budinger.
Dr. Fiala goes in on Saturdays and runs a free clinic conducting sleep studies for patients and outfits them with devices that they need to improve their conditions, said Dr. Budinger.
“And these patients are the severest of the severe patients,” he said. “These are people that have severe sleep apnea that are driving around the roads, oftentimes don’t have insurance because they’re also precluded from having auto insurance. So, this is really something that not just benefits these patients but benefits our whole community.”
The fact that Dr. Fiala followed through on something that all doctors aspire to do — and in the middle of a very busy training program — is something that Dr. Budinger said makes him stand out in a big way.
“If you talk to any of our trainees or young faculty, everybody’s interested in addressing the issue of health disparities,” said Dr. Budinger. “Justin looked at that and said, ‘Well, you know, I’m not interested in talking about it. What can I do about this problem? And how can I actually get boots on the ground and help?’ That requires a big activation energy that many people don’t have.”
Lesson #4: Be a People-Person and a Patient-Person
When hiring employees at American Family Care in Portland, Oregon, Andrew Miller, MD, director of provider training, is always on the lookout for young MDs with emotional intelligence and a good bedside manner. He has been recently blown away, however, by a young physician’s assistant named Joseph Van Bindsbergen, PA-C, who was described as “all-around wonderful” during his reference check.
“Having less than 6 months of experience out of school, he is our highest ranked provider, whether it’s a nurse practitioner, PA, or doctor, in terms of patient satisfaction,” said Dr. Miller. The young PA has an “unprecedented perfect score” on his NPS rating.
Why? Patients said they’ve never felt as heard as they felt with Van Bindsbergen.
“That’s the thing I think that the up-and-coming providers should be focusing on is making your patients feel heard,” explained Dr. Miller. Van Bindsbergen is great at building rapport with a patient, whether they are 6 or 96. “He doesn’t just ask about sore throat symptoms. He asks, ‘what is the impact on your life of the sore throat? How does it affect your family or your work? What do you think this could be besides just strep? What are your concerns?’ ”
Dr. Miller said the magic of Van Bindsbergen is that he has an innate ability to look at patients “not just as a diagnosis but as a person, which they love.”
Lesson #5: Remember to Make That Difference With Each Patient
Doctors are used to swooping in and seeing a patient, ordering further testing if needed, and then moving on to the next patient. But one young intern at the start of his medical career broke this mold by giving a very anxious patient some much-needed support.
“There was a resident who was working overnight, and this poor young woman came in who had a new diagnosis of an advanced illness and a lot of anxiety around her condition, the newness of it, and the impact this is going to have on her family and her life,” said Elizabeth Horn Prsic, MD, assistant professor at Yale School of Medicine and firm chief for medical oncology and the director of Adult Inpatient Palliative Care.
Dr. Prsic found out the next morning that this trainee accompanied the patient to the MRI and held her hand as much as he was allowed to throughout the entire experience. “I was like, ‘wait you went down with her to radiology?’ And he’s like, ‘Yes, I was there the whole time,’ ” she recalled.
This gesture not only helped the patient feel calmer after receiving a potentially life-altering diagnosis but also helped ensure the test results were as clear as possible.
“If the study is not done well and a patient is moving or uncomfortable, it has to be stopped early or paused,” said Dr. Prsic. “Then the study is not very useful. In situations like these, medical decisions may be made based on imperfect data. The fact that we had this full complete good quality scan helped us get the care that she needed in a much timelier manner to help her and to move along the care that she that was medically appropriate for her.”
Dr. Prsic got emotional reflecting on the experience. Working at Yale, she saw a ton of intelligent doctors come through the ranks. But this gesture, she said, should serve as a reminder that “you don’t need to be the smartest person in the room to just be there for a patient. It was pure empathic presence and human connection. It gave me hope in the next generation of physicians.”
A version of this article appeared on Medscape.com.
Genetic Signatures May Predict CAR T Responders
“Our transcriptomic analysis of ZUMA-7 dataset identified novel gene expression signatures predictive of outcome with axi-cel,” the authors reported in research presented at the annual meeting of the American Association for Cancer Research earlier in April. “These gene expression signatures could support risk-stratification of LBCL patients.”
The results are from a subanalysis of the phase 3 ZUMA-7 trial in which patients with early relapsed or primary refractory LBCL were treated with axi-cel, administered as a one-time dose in the second-line setting.
Long-term results from the trial showed a 4-year overall survival of 54.6% with axi-cel versus 46.0% with the standard of care (P = .03), with a median rate of progression-free survival of 14.7 months with axi-cel versus 3.7 months in the standard-second-line treatment.
In the study, the authors noted that, “although the use of axi-cel resulted in long-term survival in more than half of treated patients, it is important to continue to strive to improve patient outcomes.”
Following up on that, senior author Simone Filosto, of Kite, a Gilead Company, of Santa Monica, California, and colleagues launched their analysis of the genetic profiles of those who did and did not have favorable responses, using data from the ZUMA-7 trial.
Using gene expression profiling with the IO-360 Nanostring gene expression panel of 769 genes, they evaluated pretreated LBCL tumor samples from 134 of the patients treated with axi-cel.
After multivariate adjustment, the results showed that those with a distinctive 6-transcript genetic expression signature, consisting of CD19, CD45RA, CCL22, KLRK1, SOX11, and SIGLEC5, had a significantly higher rate of event-free survival (hazard ratio [HR], 0.27; P = 1.82 x 10-8), as well as progression-free survival (HR, 0.27; P = 1.35 x 10-7) after treatment with axi-cel, compared with those who did not have the signature.
The authors speculated that “the 6-gene expression signature may capture lymphomas with abundant adhesion molecules, a relatively low inflammation, and abundant expression of the targeted antigen (CD19).”
Conversely, the analysis showed that increased levels of an unfavorable 17-transcript gene expression signature had a strong negative correlation with event-free survival (HR, 6.19; P = 1.51 x 10-13) and progression-free survival (HR, 7.58; P = 2.70 x 10-14).
The 17-transcript signature included CD45RO, BCL2, IL-18R1, TNFSF4 [OX40L], KLRB1 [CD161], KIR3DL2, ITGB8, DUSP5, GPC4, PSMB5, RPS6KB1, SERPINA9, NBN, GLUD1, ESR1, ARID1A, and SLC16A1.
“The 17-gene expression signature is consistent with a high level of immune infiltration and inflammation paralleled by the activation of immune-escape mechanisms, such as the upregulation of anti-apoptotic genes,” the authors explain.
Of note, the 17-gene expression signature was elevated among 18 patients who progressed after axi-cel treatment.
Importantly, the gene expression signatures were not associated with outcomes observed among patients receiving second-line standard of care in the ZUMA-7 trial. And the signatures also did not correspond with outcomes following first-line R-CHOP chemotherapy reported in two online datasets, indicating their predictive rather than prognostic value.
Commenting on the findings, Marco Ruella, MD, noted that “stratifying the [CAR T-treated] patients is extremely important given that only a subset of them, 30%-40%, will experience long-term remission.”
“In an ideal scenario, we would want to treat only the patients who would benefit from such a complex and expensive therapy,” underscored Dr. Ruella, assistant professor in the Division of Hematology/Oncology and the Center for Cellular Immunotherapies and Scientific Director of the Lymphoma Program at the Hospital of the University of Pennsylvania in Philadelphia.
A key caveat is that the results need more validation before they true gain clinical value, he noted.
“We need more data before we can use such a score in the clinic as we would need to be absolutely confident on the predictive value of such a score in additional confirmatory cohorts.”
Furthermore, caution is warranted in avoiding excluding any patients unnecessarily, he added.
“Only if there are approximately zero chances of response would we be able to exclude a patient from a treatment,” Dr. Ruella noted. “If the chance of long-term cure are minimal but still present, it might still make sense for the patient.”
Nevertheless, such findings advance the understanding of the therapy’s implication in a meaningful way, he said.
“I think this study [and similar others] are important studies that help us better understand the mechanisms of relapse,” he said.
“Translationally, we are getting closer to reaching a point where we can precisely predict outcomes and, perhaps in the future, select the patients that would benefit the most from these treatments.”
Dr. Filosto and other authors are employees of Kite, which manufactures axi-cel. Dr. Ruella treats patients with CAR T products that have been licensed to Novartis, Kite, and Vittoria Bio.
“Our transcriptomic analysis of ZUMA-7 dataset identified novel gene expression signatures predictive of outcome with axi-cel,” the authors reported in research presented at the annual meeting of the American Association for Cancer Research earlier in April. “These gene expression signatures could support risk-stratification of LBCL patients.”
The results are from a subanalysis of the phase 3 ZUMA-7 trial in which patients with early relapsed or primary refractory LBCL were treated with axi-cel, administered as a one-time dose in the second-line setting.
Long-term results from the trial showed a 4-year overall survival of 54.6% with axi-cel versus 46.0% with the standard of care (P = .03), with a median rate of progression-free survival of 14.7 months with axi-cel versus 3.7 months in the standard-second-line treatment.
In the study, the authors noted that, “although the use of axi-cel resulted in long-term survival in more than half of treated patients, it is important to continue to strive to improve patient outcomes.”
Following up on that, senior author Simone Filosto, of Kite, a Gilead Company, of Santa Monica, California, and colleagues launched their analysis of the genetic profiles of those who did and did not have favorable responses, using data from the ZUMA-7 trial.
Using gene expression profiling with the IO-360 Nanostring gene expression panel of 769 genes, they evaluated pretreated LBCL tumor samples from 134 of the patients treated with axi-cel.
After multivariate adjustment, the results showed that those with a distinctive 6-transcript genetic expression signature, consisting of CD19, CD45RA, CCL22, KLRK1, SOX11, and SIGLEC5, had a significantly higher rate of event-free survival (hazard ratio [HR], 0.27; P = 1.82 x 10-8), as well as progression-free survival (HR, 0.27; P = 1.35 x 10-7) after treatment with axi-cel, compared with those who did not have the signature.
The authors speculated that “the 6-gene expression signature may capture lymphomas with abundant adhesion molecules, a relatively low inflammation, and abundant expression of the targeted antigen (CD19).”
Conversely, the analysis showed that increased levels of an unfavorable 17-transcript gene expression signature had a strong negative correlation with event-free survival (HR, 6.19; P = 1.51 x 10-13) and progression-free survival (HR, 7.58; P = 2.70 x 10-14).
The 17-transcript signature included CD45RO, BCL2, IL-18R1, TNFSF4 [OX40L], KLRB1 [CD161], KIR3DL2, ITGB8, DUSP5, GPC4, PSMB5, RPS6KB1, SERPINA9, NBN, GLUD1, ESR1, ARID1A, and SLC16A1.
“The 17-gene expression signature is consistent with a high level of immune infiltration and inflammation paralleled by the activation of immune-escape mechanisms, such as the upregulation of anti-apoptotic genes,” the authors explain.
Of note, the 17-gene expression signature was elevated among 18 patients who progressed after axi-cel treatment.
Importantly, the gene expression signatures were not associated with outcomes observed among patients receiving second-line standard of care in the ZUMA-7 trial. And the signatures also did not correspond with outcomes following first-line R-CHOP chemotherapy reported in two online datasets, indicating their predictive rather than prognostic value.
Commenting on the findings, Marco Ruella, MD, noted that “stratifying the [CAR T-treated] patients is extremely important given that only a subset of them, 30%-40%, will experience long-term remission.”
“In an ideal scenario, we would want to treat only the patients who would benefit from such a complex and expensive therapy,” underscored Dr. Ruella, assistant professor in the Division of Hematology/Oncology and the Center for Cellular Immunotherapies and Scientific Director of the Lymphoma Program at the Hospital of the University of Pennsylvania in Philadelphia.
A key caveat is that the results need more validation before they true gain clinical value, he noted.
“We need more data before we can use such a score in the clinic as we would need to be absolutely confident on the predictive value of such a score in additional confirmatory cohorts.”
Furthermore, caution is warranted in avoiding excluding any patients unnecessarily, he added.
“Only if there are approximately zero chances of response would we be able to exclude a patient from a treatment,” Dr. Ruella noted. “If the chance of long-term cure are minimal but still present, it might still make sense for the patient.”
Nevertheless, such findings advance the understanding of the therapy’s implication in a meaningful way, he said.
“I think this study [and similar others] are important studies that help us better understand the mechanisms of relapse,” he said.
“Translationally, we are getting closer to reaching a point where we can precisely predict outcomes and, perhaps in the future, select the patients that would benefit the most from these treatments.”
Dr. Filosto and other authors are employees of Kite, which manufactures axi-cel. Dr. Ruella treats patients with CAR T products that have been licensed to Novartis, Kite, and Vittoria Bio.
“Our transcriptomic analysis of ZUMA-7 dataset identified novel gene expression signatures predictive of outcome with axi-cel,” the authors reported in research presented at the annual meeting of the American Association for Cancer Research earlier in April. “These gene expression signatures could support risk-stratification of LBCL patients.”
The results are from a subanalysis of the phase 3 ZUMA-7 trial in which patients with early relapsed or primary refractory LBCL were treated with axi-cel, administered as a one-time dose in the second-line setting.
Long-term results from the trial showed a 4-year overall survival of 54.6% with axi-cel versus 46.0% with the standard of care (P = .03), with a median rate of progression-free survival of 14.7 months with axi-cel versus 3.7 months in the standard-second-line treatment.
In the study, the authors noted that, “although the use of axi-cel resulted in long-term survival in more than half of treated patients, it is important to continue to strive to improve patient outcomes.”
Following up on that, senior author Simone Filosto, of Kite, a Gilead Company, of Santa Monica, California, and colleagues launched their analysis of the genetic profiles of those who did and did not have favorable responses, using data from the ZUMA-7 trial.
Using gene expression profiling with the IO-360 Nanostring gene expression panel of 769 genes, they evaluated pretreated LBCL tumor samples from 134 of the patients treated with axi-cel.
After multivariate adjustment, the results showed that those with a distinctive 6-transcript genetic expression signature, consisting of CD19, CD45RA, CCL22, KLRK1, SOX11, and SIGLEC5, had a significantly higher rate of event-free survival (hazard ratio [HR], 0.27; P = 1.82 x 10-8), as well as progression-free survival (HR, 0.27; P = 1.35 x 10-7) after treatment with axi-cel, compared with those who did not have the signature.
The authors speculated that “the 6-gene expression signature may capture lymphomas with abundant adhesion molecules, a relatively low inflammation, and abundant expression of the targeted antigen (CD19).”
Conversely, the analysis showed that increased levels of an unfavorable 17-transcript gene expression signature had a strong negative correlation with event-free survival (HR, 6.19; P = 1.51 x 10-13) and progression-free survival (HR, 7.58; P = 2.70 x 10-14).
The 17-transcript signature included CD45RO, BCL2, IL-18R1, TNFSF4 [OX40L], KLRB1 [CD161], KIR3DL2, ITGB8, DUSP5, GPC4, PSMB5, RPS6KB1, SERPINA9, NBN, GLUD1, ESR1, ARID1A, and SLC16A1.
“The 17-gene expression signature is consistent with a high level of immune infiltration and inflammation paralleled by the activation of immune-escape mechanisms, such as the upregulation of anti-apoptotic genes,” the authors explain.
Of note, the 17-gene expression signature was elevated among 18 patients who progressed after axi-cel treatment.
Importantly, the gene expression signatures were not associated with outcomes observed among patients receiving second-line standard of care in the ZUMA-7 trial. And the signatures also did not correspond with outcomes following first-line R-CHOP chemotherapy reported in two online datasets, indicating their predictive rather than prognostic value.
Commenting on the findings, Marco Ruella, MD, noted that “stratifying the [CAR T-treated] patients is extremely important given that only a subset of them, 30%-40%, will experience long-term remission.”
“In an ideal scenario, we would want to treat only the patients who would benefit from such a complex and expensive therapy,” underscored Dr. Ruella, assistant professor in the Division of Hematology/Oncology and the Center for Cellular Immunotherapies and Scientific Director of the Lymphoma Program at the Hospital of the University of Pennsylvania in Philadelphia.
A key caveat is that the results need more validation before they true gain clinical value, he noted.
“We need more data before we can use such a score in the clinic as we would need to be absolutely confident on the predictive value of such a score in additional confirmatory cohorts.”
Furthermore, caution is warranted in avoiding excluding any patients unnecessarily, he added.
“Only if there are approximately zero chances of response would we be able to exclude a patient from a treatment,” Dr. Ruella noted. “If the chance of long-term cure are minimal but still present, it might still make sense for the patient.”
Nevertheless, such findings advance the understanding of the therapy’s implication in a meaningful way, he said.
“I think this study [and similar others] are important studies that help us better understand the mechanisms of relapse,” he said.
“Translationally, we are getting closer to reaching a point where we can precisely predict outcomes and, perhaps in the future, select the patients that would benefit the most from these treatments.”
Dr. Filosto and other authors are employees of Kite, which manufactures axi-cel. Dr. Ruella treats patients with CAR T products that have been licensed to Novartis, Kite, and Vittoria Bio.
FROM AACR 2024