Patient & Survivor Care

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are associated with an increased risk for breast cancer, and CHIP is associated with increased mortality in patients with colon cancer, according to the authors of new research.

These findings, drawn from almost 11,000 patients in the Women’s Health Initiative (WHI) study, add further evidence that CHIP and mCA drive solid tumor risk, alongside known associations with hematologic malignancies, reported lead author Pinkal Desai, MD, associate professor of medicine and clinical director of molecular aging at Englander Institute for Precision Medicine, Weill Cornell Medical College, New York City, and colleagues.
 

How This Study Differs From Others of Breast Cancer Risk Factors

“The independent effect of CHIP and mCA on risk and mortality from solid tumors has not been elucidated due to lack of detailed data on mortality outcomes and risk factors,” the investigators wrote in Cancer, although some previous studies have suggested a link.

In particular, the investigators highlighted a 2022 UK Biobank study, which reported an association between CHIP and lung cancer and a borderline association with breast cancer that did not quite reach statistical significance.

But the UK Biobank study was confined to a UK population, Dr. Desai noted in an interview, and the data were less detailed than those in the present investigation.

“In terms of risk, the part that was lacking in previous studies was a comprehensive assessment of risk factors that increase risk for all these cancers,” Dr. Desai said. “For example, for breast cancer, we had very detailed data on [participants’] Gail risk score, which is known to impact breast cancer risk. We also had mammogram data and colonoscopy data.”

In an accompanying editorial, Koichi Takahashi, MD, PhD , and Nehali Shah, BS, of The University of Texas MD Anderson Cancer Center, Houston, Texas, pointed out the same UK Biobank findings, then noted that CHIP has also been linked with worse overall survival in unselected cancer patients. Still, they wrote, “the impact of CH on cancer risk and mortality remains controversial due to conflicting data and context‐dependent effects,” necessitating studies like this one by Dr. Desai and colleagues.
 

How Was the Relationship Between CHIP, MCA, and Solid Tumor Risk Assessed?

To explore possible associations between CHIP, mCA, and solid tumors, the investigators analyzed whole genome sequencing data from 10,866 women in the WHI, a multi-study program that began in 1992 and involved 161,808 women in both observational and clinical trial cohorts.

In 2002, the first big data release from the WHI suggested that hormone replacement therapy (HRT) increased breast cancer risk, leading to widespread reduction in HRT use.

More recent reports continue to shape our understanding of these risks, suggesting differences across cancer types. For breast cancer, the WHI data suggested that HRT-associated risk was largely driven by formulations involving progesterone and estrogen, whereas estrogen-only formulations, now more common, are generally considered to present an acceptable risk profile for suitable patients.

The new study accounted for this potential HRT-associated risk, including by adjusting for patients who received HRT, type of HRT received, and duration of HRT received. According to Desai, this approach is commonly used when analyzing data from the WHI, nullifying concerns about the potentially deleterious effects of the hormones used in the study.

“Our question was not ‘does HRT cause cancer?’ ” Dr. Desai said in an interview. “But HRT can be linked to breast cancer risk and has a potential to be a confounder, and hence the above methodology.

“So I can say that the confounding/effect modification that HRT would have contributed to in the relationship between exposure (CH and mCA) and outcome (cancer) is well adjusted for as described above. This is standard in WHI analyses,” she continued.

“Every Women’s Health Initiative analysis that comes out — not just for our study — uses a standard method ... where you account for hormonal therapy,” Dr. Desai added, again noting that many other potential risk factors were considered, enabling a “detailed, robust” analysis.

Dr. Takahashi and Ms. Shah agreed. “A notable strength of this study is its adjustment for many confounding factors,” they wrote. “The cohort’s well‐annotated data on other known cancer risk factors allowed for a robust assessment of CH’s independent risk.”
 

How Do Findings Compare With Those of the UK Biobank Study?

CHIP was associated with a 30% increased risk for breast cancer (hazard ratio [HR], 1.30; 95% CI, 1.03-1.64; P = .02), strengthening the borderline association reported by the UK Biobank study.

In contrast with the UK Biobank study, CHIP was not associated with lung cancer risk, although this may have been caused by fewer cases of lung cancer and a lack of male patients, Dr. Desai suggested.

“The discrepancy between the studies lies in the risk of lung cancer, although the point estimate in the current study suggested a positive association,” wrote Dr. Takahashi and Ms. Shah.

As in the UK Biobank study, CHIP was not associated with increased risk of developing colorectal cancer.

Mortality analysis, however, which was not conducted in the UK Biobank study, offered a new insight: Patients with existing colorectal cancer and CHIP had a significantly higher mortality risk than those without CHIP. Before stage adjustment, risk for mortality among those with colorectal cancer and CHIP was fourfold higher than those without CHIP (HR, 3.99; 95% CI, 2.41-6.62; P < .001). After stage adjustment, CHIP was still associated with a twofold higher mortality risk (HR, 2.50; 95% CI, 1.32-4.72; P = .004).

The investigators’ first mCA analyses, which employed a cell fraction cutoff greater than 3%, were unfruitful. But raising the cell fraction threshold to 5% in an exploratory analysis showed that autosomal mCA was associated with a 39% increased risk for breast cancer (HR, 1.39; 95% CI, 1.06-1.83; P = .01). No such associations were found between mCA and colorectal or lung cancer, regardless of cell fraction threshold.

The original 3% cell fraction threshold was selected on the basis of previous studies reporting a link between mCA and hematologic malignancies at this cutoff, Dr. Desai said.

She and her colleagues said a higher 5% cutoff might be needed, as they suspected that the link between mCA and solid tumors may not be causal, requiring a higher mutation rate.
 

Why Do Results Differ Between These Types of Studies?

Dr. Takahashi and Ms. Shah suggested that one possible limitation of the new study, and an obstacle to comparing results with the UK Biobank study and others like it, goes beyond population heterogeneity; incongruent findings could also be explained by differences in whole genome sequencing (WGS) technique.

“Although WGS allows sensitive detection of mCA through broad genomic coverage, it is less effective at detecting CHIP with low variant allele frequency (VAF) due to its relatively shallow depth (30x),” they wrote. “Consequently, the prevalence of mCA (18.8%) was much higher than that of CHIP (8.3%) in this cohort, contrasting with other studies using deeper sequencing.” As a result, the present study may have underestimated CHIP prevalence because of shallow sequencing depth.

“This inconsistency is a common challenge in CH population studies due to the lack of standardized methodologies and the frequent reliance on preexisting data not originally intended for CH detection,” Dr. Takahashi and Ms. Shah said.

Even so, despite the “heavily context-dependent” nature of these reported risks, the body of evidence to date now offers a convincing biological rationale linking CH with cancer development and outcomes, they added.
 

How Do the CHIP- and mCA-associated Risks Differ Between Solid Tumors and Blood Cancers?

“[These solid tumor risks are] not causal in the way CHIP mutations are causal for blood cancers,” Dr. Desai said. “Here we are talking about solid tumor risk, and it’s kind of scattered. It’s not just breast cancer ... there’s also increased colon cancer mortality. So I feel these mutations are doing something different ... they are sort of an added factor.”

Specific mechanisms remain unclear, Dr. Desai said, although she speculated about possible impacts on the inflammatory state or alterations to the tumor microenvironment.

“These are blood cells, right?” Dr. Desai asked. “They’re everywhere, and they’re changing something inherently in these tumors.”
 

Future research and therapeutic development

Siddhartha Jaiswal, MD, PhD, assistant professor in the Department of Pathology at Stanford University in California, whose lab focuses on clonal hematopoiesis, said the causality question is central to future research.

“The key question is, are these mutations acting because they alter the function of blood cells in some way to promote cancer risk, or is it reflective of some sort of shared etiology that’s not causal?” Dr. Jaiswal said in an interview.

Available data support both possibilities.

On one side, “reasonable evidence” supports the noncausal view, Dr. Jaiswal noted, because telomere length is one of the most common genetic risk factors for clonal hematopoiesis and also for solid tumors, suggesting a shared genetic factor. On the other hand, CHIP and mCA could be directly protumorigenic via conferred disturbances of immune cell function.

When asked if both causal and noncausal factors could be at play, Dr. Jaiswal said, “yeah, absolutely.”

The presence of a causal association could be promising from a therapeutic standpoint.

“If it turns out that this association is driven by a direct causal effect of the mutations, perhaps related to immune cell function or dysfunction, then targeting that dysfunction could be a therapeutic path to improve outcomes in people, and there’s a lot of interest in this,” Dr. Jaiswal said. He went on to explain how a trial exploring this approach via interleukin-8 inhibition in lung cancer fell short.

Yet earlier intervention may still hold promise, according to experts.

“[This study] provokes the hypothesis that CH‐targeted interventions could potentially reduce cancer risk in the future,” Dr. Takahashi and Ms. Shah said in their editorial.

The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The investigators disclosed relationships with Eli Lilly, AbbVie, Celgene, and others. Dr. Jaiswal reported stock equity in a company that has an interest in clonal hematopoiesis.

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

This transcript has been edited for clarity. 

I’d like to talk about a very different topic from what I normally discuss, which is probably relatively rarely addressed in clinical conversations among clinicians. There was a very provocative commentary that appeared in JCO Oncology Practice, titled “Hollywood’s Take on Oncology: Portrayal of Cancer in Movies, 2010-2020.”

All of us, as we grow up — as kids, adolescents, young adults, adults, and older individuals — watch television and movies. The older of us know that the doctor in everybody’s home that we all wanted was Marcus Welby. Of course, there was Dr. Kildare, ER, Grey’s Anatomy, and St. Elsewhere. There was Love Story and Brian’s Song. We all know about these. 

This particular review was fascinating. The authors looked at 100 English-language movies that had cancer included in the storyline over the past decade. They asked some relatively simple questions: How did they discuss it? What were the tumor types they discussed? What were the outcomes? 

The question is, what is the public seeing? If you watch these movies and you don’t have family experience or personal experience with cancer, what do you think about cancer? Maybe this is what you know about it. Despite what the National Cancer Institute or the American Society of Clinical Oncology tells you, this may be what you know.

What they showed was really quite interesting. Only one third of the movies even said the cancer type, so in two thirds, you just knew they had “cancer.”

There is another very interesting phenomenon. What do you think was the most common cancer type when they did define the cancer? It was brain tumors, even though we know that brain tumors are certainly not even within the top 10. They’re obviously very serious cancers, but if you’re talking about common cancers, brain cancer doesn’t rank in the top 10, and it was the most common cancer on these shows.

The authors of this paper made the point of whether this would be an opportunity for filmmakers. Again, with the storyline, they’re trying to sell a product here, but wouldn’t this be the opportunity to provide some information about the reality of cancer? They could emphasize the fact that smokers get lung cancer. In my opinion, they could discuss cervical cancer and comment that if HPV vaccination had been done, maybe this would not have happened.

They noted that the majority of cancers in these movies were incurable, and they commented that that’s not the reality today. Today, obviously, many of our cancers that weren’t curable have become quite curable for a percentage of patients, in addition to which, obviously, with early detection, we have a very high cure rate. How about trying to get that message out, too, that we’ve actually had increasing success?

They commented that there was very rarely, if ever, a conversation about multidisciplinary care, that somehow there are multiple doctors with multiple specialties involved. They noted that this is potentially a very important message to give out. They commented that in 12 of these movies, the patient refused cancer care. Again, that happens, but it’s clearly a rare event today. Maybe this is not really a very accurate depiction of what’s going on.

They commented on the fact that, obviously, we’re going back through the past 10 years, so there were no patients who received immunotherapy or targeted therapy. Again, the goal here is not to sell oncology care but to be accurate, or more accurate, about the state of treatment to the extent you can.

They noted that, in fact, there was essentially very little, if any, comment on palliative care or hospice care. The final point they made is that there was very little conversation in these movies about what we now recognize as financial distress in many of our patients. That’s an unfortunate reality and perhaps that might come in the future.

Again, the point of this was not to tell Hollywood how to make their movies but to have the oncology community recognize that if their patients or the families of their patients are seeing these movies, they are not getting a very accurate picture of what is happening in the oncology world today and that some education may very well be required.

Maurie Markman is Professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California, and President of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed the following relevant financial relationships: income in an amount equal to or greater than $250 from: GlaxoSmithKline; AstraZeneca.

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

This transcript has been edited for clarity. 

I’d like to talk about a very different topic from what I normally discuss, which is probably relatively rarely addressed in clinical conversations among clinicians. There was a very provocative commentary that appeared in JCO Oncology Practice, titled “Hollywood’s Take on Oncology: Portrayal of Cancer in Movies, 2010-2020.”

All of us, as we grow up — as kids, adolescents, young adults, adults, and older individuals — watch television and movies. The older of us know that the doctor in everybody’s home that we all wanted was Marcus Welby. Of course, there was Dr. Kildare, ER, Grey’s Anatomy, and St. Elsewhere. There was Love Story and Brian’s Song. We all know about these. 

This particular review was fascinating. The authors looked at 100 English-language movies that had cancer included in the storyline over the past decade. They asked some relatively simple questions: How did they discuss it? What were the tumor types they discussed? What were the outcomes? 

The question is, what is the public seeing? If you watch these movies and you don’t have family experience or personal experience with cancer, what do you think about cancer? Maybe this is what you know about it. Despite what the National Cancer Institute or the American Society of Clinical Oncology tells you, this may be what you know.

What they showed was really quite interesting. Only one third of the movies even said the cancer type, so in two thirds, you just knew they had “cancer.”

There is another very interesting phenomenon. What do you think was the most common cancer type when they did define the cancer? It was brain tumors, even though we know that brain tumors are certainly not even within the top 10. They’re obviously very serious cancers, but if you’re talking about common cancers, brain cancer doesn’t rank in the top 10, and it was the most common cancer on these shows.

The authors of this paper made the point of whether this would be an opportunity for filmmakers. Again, with the storyline, they’re trying to sell a product here, but wouldn’t this be the opportunity to provide some information about the reality of cancer? They could emphasize the fact that smokers get lung cancer. In my opinion, they could discuss cervical cancer and comment that if HPV vaccination had been done, maybe this would not have happened.

They noted that the majority of cancers in these movies were incurable, and they commented that that’s not the reality today. Today, obviously, many of our cancers that weren’t curable have become quite curable for a percentage of patients, in addition to which, obviously, with early detection, we have a very high cure rate. How about trying to get that message out, too, that we’ve actually had increasing success?

They commented that there was very rarely, if ever, a conversation about multidisciplinary care, that somehow there are multiple doctors with multiple specialties involved. They noted that this is potentially a very important message to give out. They commented that in 12 of these movies, the patient refused cancer care. Again, that happens, but it’s clearly a rare event today. Maybe this is not really a very accurate depiction of what’s going on.

They commented on the fact that, obviously, we’re going back through the past 10 years, so there were no patients who received immunotherapy or targeted therapy. Again, the goal here is not to sell oncology care but to be accurate, or more accurate, about the state of treatment to the extent you can.

They noted that, in fact, there was essentially very little, if any, comment on palliative care or hospice care. The final point they made is that there was very little conversation in these movies about what we now recognize as financial distress in many of our patients. That’s an unfortunate reality and perhaps that might come in the future.

Again, the point of this was not to tell Hollywood how to make their movies but to have the oncology community recognize that if their patients or the families of their patients are seeing these movies, they are not getting a very accurate picture of what is happening in the oncology world today and that some education may very well be required.

Maurie Markman is Professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California, and President of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed the following relevant financial relationships: income in an amount equal to or greater than $250 from: GlaxoSmithKline; AstraZeneca.

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

This transcript has been edited for clarity. 

I’d like to talk about a very different topic from what I normally discuss, which is probably relatively rarely addressed in clinical conversations among clinicians. There was a very provocative commentary that appeared in JCO Oncology Practice, titled “Hollywood’s Take on Oncology: Portrayal of Cancer in Movies, 2010-2020.”

All of us, as we grow up — as kids, adolescents, young adults, adults, and older individuals — watch television and movies. The older of us know that the doctor in everybody’s home that we all wanted was Marcus Welby. Of course, there was Dr. Kildare, ER, Grey’s Anatomy, and St. Elsewhere. There was Love Story and Brian’s Song. We all know about these. 

This particular review was fascinating. The authors looked at 100 English-language movies that had cancer included in the storyline over the past decade. They asked some relatively simple questions: How did they discuss it? What were the tumor types they discussed? What were the outcomes? 

The question is, what is the public seeing? If you watch these movies and you don’t have family experience or personal experience with cancer, what do you think about cancer? Maybe this is what you know about it. Despite what the National Cancer Institute or the American Society of Clinical Oncology tells you, this may be what you know.

What they showed was really quite interesting. Only one third of the movies even said the cancer type, so in two thirds, you just knew they had “cancer.”

There is another very interesting phenomenon. What do you think was the most common cancer type when they did define the cancer? It was brain tumors, even though we know that brain tumors are certainly not even within the top 10. They’re obviously very serious cancers, but if you’re talking about common cancers, brain cancer doesn’t rank in the top 10, and it was the most common cancer on these shows.

The authors of this paper made the point of whether this would be an opportunity for filmmakers. Again, with the storyline, they’re trying to sell a product here, but wouldn’t this be the opportunity to provide some information about the reality of cancer? They could emphasize the fact that smokers get lung cancer. In my opinion, they could discuss cervical cancer and comment that if HPV vaccination had been done, maybe this would not have happened.

They noted that the majority of cancers in these movies were incurable, and they commented that that’s not the reality today. Today, obviously, many of our cancers that weren’t curable have become quite curable for a percentage of patients, in addition to which, obviously, with early detection, we have a very high cure rate. How about trying to get that message out, too, that we’ve actually had increasing success?

They commented that there was very rarely, if ever, a conversation about multidisciplinary care, that somehow there are multiple doctors with multiple specialties involved. They noted that this is potentially a very important message to give out. They commented that in 12 of these movies, the patient refused cancer care. Again, that happens, but it’s clearly a rare event today. Maybe this is not really a very accurate depiction of what’s going on.

They commented on the fact that, obviously, we’re going back through the past 10 years, so there were no patients who received immunotherapy or targeted therapy. Again, the goal here is not to sell oncology care but to be accurate, or more accurate, about the state of treatment to the extent you can.

They noted that, in fact, there was essentially very little, if any, comment on palliative care or hospice care. The final point they made is that there was very little conversation in these movies about what we now recognize as financial distress in many of our patients. That’s an unfortunate reality and perhaps that might come in the future.

Again, the point of this was not to tell Hollywood how to make their movies but to have the oncology community recognize that if their patients or the families of their patients are seeing these movies, they are not getting a very accurate picture of what is happening in the oncology world today and that some education may very well be required.

Maurie Markman is Professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California, and President of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed the following relevant financial relationships: income in an amount equal to or greater than $250 from: GlaxoSmithKline; AstraZeneca.

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

This transcript has been edited for clarity.
 

Benjamin L. Schlechter, MD: Today we’re discussing liver transplant for metastatic colorectal cancer with our guest, Dr. Martin Dib. Dr. Dib is the director of the Hepatobiliary Surgery and Living Donor Program at Beth Israel Deaconess Medical Center here in Boston, and a Harvard Medical School faculty member.

He was previously at the Pontificia Universidad Católica de Chile, a leading international institution investigating the role of liver transplant in colorectal cancer, among other diseases. Dr. Dib, before we move to our discussion, I’d like to hear a bit about your pathway to becoming a transplant surgeon. How did you end up working on colorectal cancer and liver transplants in this field?

Martin J. Dib, MD: Thank you so much, Dr. Schlechter. I am originally from Chile. I had an opportunity to come to Beth Israel Deaconess Medical Center after medical school and I did liver regeneration research at the transplant center. After that, I was lucky enough to match as a general surgery resident at Beth Israel Deaconess.

This is my alma mater and I was able to graduate as a surgeon here. You and I had some paths together. After graduating from Harvard as a surgeon, I was trained in liver transplant, abdominal transplant, surgical oncology, and hepatobiliary surgery at the University of Toronto.

I have been developing this passion for being able to transplant cancer patients and use organ transplant techniques to be able to do complex resections for cancer.

Dr. Schlechter: Let’s talk about the topic for today, which is liver transplant and colorectal cancer. I’ll be honest — this is not a very familiar topic for a lot of oncologists. There are a lot of details that I think are new to us as oncologists. We need to expand this conversation to get access to patients for this.

First and foremost, can you talk about some of the parameters for a resectable liver metastasis vs unresectable disease that would be an indication for a liver transplant?

Dr. Dib: I think this is a very interesting topic because liver transplantation for cancer is not new. Liver transplantation started in the 1960s when people started doing liver transplants for advanced liver tumors. The problem is that they were selecting patients who had very advanced — and poor tumor biology — tumors. The outcomes were not good.

It was only in 1996 when the Milan criteria started. Mazzaferro and colleagues, using strict patient selection, were able to do liver transplant for selected hepatocellular carcinoma patients. Having those excellent outcomes in selecting patients opened the field for what we now call transplant oncology, which is using selection criteria and using other methods to be able to select which patients will do well after transplantation, even with immunosuppression.

Liver transplantation for colorectal metastasis was used at the very beginning of the era of liver transplantation, but with very poor outcomes. It was abandoned because of the outcomes. It is exciting to see that after 20 years of not doing it, there was a group in Norway that started again. They are doing liver transplants for colorectal metastases (mets), but with very selected patients.

In Norway, they had a very unusual setting where they had more liver donors than patients on the list waiting for liver transplant. So they can’t share these livers and we’re all jealous, right? Every single country in the West struggles because we don’t have enough livers for the rest of the list. And they had a lot of livers to be able to transplant people.

They decided to transplant some selected patients with colorectal mets that were unresectable. And the surprise was that they found that they were able to get a 60% survival at 5 years. And so that was new. After that, in Norway, they started showing this data to other centers in the world. It wasn’t until this year that we could see not only the long-term data and long-term outcomes of using liver transplantation for unresectable colorectal mets, but also we’re now having data from a prospective clinical trial from France.

It was three countries in the prospective clinical trial: France, Belgium, and Italy. We now see that we have a little stronger data to support the use of liver transplants for unresectable colorectal mets.

Dr. Schlechter: That’s the TRANSMET study you’re referencing that was presented at ASCO in the late-breaking abstract session in 2024, and then more recently in The Lancet’s eClinicalMedicine. Both of those papers were led by René Adam. That was a cool presentation to sit through. I was in the room, and I was taking a ton of notes and there was a lot of info that came out of that.

First of all, it showed that patients who had received chemotherapy and were responding could then go on to liver transplant in that population. Impressively, 81% of the patients who were randomized to transplant received it. Frankly, that’s a big number, especially compared with the West, as you said, and in particular the US and here in New England where livers are a very precious commodity.

And even accounting for that, if you look at the intention-to-treat analysis, the 5-year overall survival in that population was 57% compared with 13% with chemotherapy. And that feels like a real number for chemotherapy. If you look at the per-protocol analysis, frankly, the numbers are higher.

It’s always a challenging assessment. What was also interesting to me was the pattern of recurrence, which in general was that recurrences were extrahepatic. So not only were patients rendered disease-free, but in general, the liver remained disease-free and only 3% of patients had liver-only recurrence and 11% had widespread metastatic disease.

The biggest group was lung metastases, at about 40%. Ultimately, they reported a progression-free survival of 17. 4 months for transplant compared with 6. 4 months with chemotherapy. On every parameter, it looks like liver transplant wins for these people. Help me out. Who are these people? How do we find these people?

What are the inclusions and exclusions for this population?

Dr. Dib: I think that’s very important. This is not a therapy that will be for every patient. These are selected patients who have liver-only unresectable colorectal mets. These are patients that don’t have any extrahepatic disease and that either the primary has been taken out already or that they have the primary present, but the plan is to take the primary and then do a liver transplantation after 3 months, hopefully after 6 months, of removing the primary.

These are patients who meet all the criteria that we have seen in terms of the best outcomes — patients that have Oslo scores of less than three. The Oslo trial, which included the SECA (Secondary Cancer)-I and SECA-II trials, basically showed that patients with a maximal tumor diameter of less than 5.5 with a pretransplant CEA (carcinoembryonic antigen) of less than 80 that do not have progression on chemotherapy, among other variables, do better. But the concept is that this is a therapy that will apply only to selected patients. That way we can continue to have adequate overall survival post-transplant that would be comparable to other diseases that we do liver transplants for.

Dr. Schlechter: Were there other biomarkers, any mutations that were included or excluded?

Dr. Dib: Yes. If you look at SECA-I, SECA-II trial outcomes, and also TRANSMET, they all say patients with BRAF mutations shouldn’t be transplanted. There are other parameters, including, for example, the site of the primary tumor. Patients with a left-sided colon primary tumor do much better than patients who have a right-sided primary tumor.

That’s not a complete contraindication, but if you look at the most updated inclusion criteria of programs, like the ones that the one that we have here at Beth Israel Deaconess and many others, the inclusion criteria protocols include patients who have only hepatic disease.

So, if there are no extrahepatic mets, the resection of the primary has been done or will be done after a multidisciplinary discussion. We want to make sure they have the absence of BRAF mutation, and that they don’t have disease progression while on chemotherapy. So hopefully we have data from enough months to be able to make sure that there’s no intrahepatic or extrahepatic progression while on chemotherapy.

And that’s including CEA and also looking at the imaging.

Dr. Schlechter: When you’re seeing a patient, how much chemo do you think they should have? What’s a good run chemotherapy-wise for these patients? Let’s say, before I refer a patient to you, how much chemo should they have? And then what should I do? Do I get a PET scan? Do I get MRI? What’s the right scanning I should do to prove there’s no extrahepatic disease before sending a patient in for consideration?

Dr. Dib: First, we need to confirm unresectability. Referring patients early is always a good measure to make sure that we’re all in agreement that it’s an unresectable patient. Having a PET scan from the very beginning is helpful because it shows the disease before doing chemotherapy.

In terms of the lines of chemotherapy, ideally in the TRANSMET trial, for example, the idea was to show tumor control for at least 3 months, with less than three lines of chemotherapy. Some patients will do that with FOLFIRI. It depends on the case.

I think some of those evaluations will need a multidisciplinary discussion. In our case, we are connected to the Norway team. We frequently talk with the Oslo team and an international community of transplant centers to get opinions on particular cases.

But I think referring patients early is a good measure. If we don’t think that they qualify, we will let the team know. We’re strictly looking at patients who have unresectable liver mets that don’t have extrahepatic disease. The idea is to do a primary tumor resection, and then get to transplantation, hopefully after 6 months. In some cases that have some concerns in terms of tumor biology, we may even extend the time from diagnosis to transplant to over 1.5 years.

Dr. Schlechter: Excellent. And what’s the experience like for these patients? In training as a resident many years ago, I saw patients with cirrhosis who went on to have a liver transplant, and that was sort of trading one disease for another. What is the posttransplant, or the remission, experience of a liver transplant for colorectal cancer like for the patient?

Dr. Dib: That’s a very important point. I think that transplantation has gotten better and better, as has chemotherapy systemic therapy. The liver transplantation experience from 20 years ago has improved dramatically. I think the quality of life of liver transplant patients after transplantation has increased quite a bit.

At Beth Israel Deaconess, we have a liver transplant program that is doing over a 100 livers a year. And when you have a high-volume center, usually the experience gets better. The time in the hospital post-transplant decreases.

In general, when we’re doing liver transplants, patients are getting extubated in the OR 30% of the time. The vast majority of patients are going home within 1 or 2 weeks. They need to have immunosuppression for the rest of their lives. We have a very good program of transplant coordinators that will help the family and the patient to live with immunosuppression and live with a transplanted organ.

But I would say that we have many, many patients, especially these patients who are not patients with cirrhosis. Their health is not as deteriorated as patients who have low MELD (model for end-stage liver disease) scores. They don’t have liver disease. They have cancer. So usually patients like that, many of them can go back to work and live a quality of life that is fairly reasonable.

Dr. Schlechter: That’s good to hear. When we hear statements like liver transplant for colon cancer, a lot of us have this picture of a much sicker population, but it’s interesting and true that the colorectal cancer population as a candidate for liver transplant is a much healthier population than the population with cirrhosis.

Let’s talk about organs and donors. Largely in the TRANSMET study, for example, that was cadaveric donors. Those were not living donors and you’ve done a lot of work on living donors. If the answer in the United States, because of limited access to organs, is going to be living donors, who are those donors?

What is that like? How do you identify them?

Dr. Dib: There’s a lot of advantages to using living donors for these patients. In any type of patient that needs a liver transplant, cadaveric donors or deceased donors is the same concept. There are two types of deceased donors: the brain-dead donors and donors after cardiac death. Those are hard to come by.

We still have 15%-20% mortality on the waiting list in the United States. We’re already still struggling to get enough donors to transplant the patients that are on the list. Now, if you add a new indication, which is unresectable colorectal mets, we need to make sure that the outcomes are equivalent to the patients who are going to be transplanted for other reasons.

Right now, for example, the 5-year overall survival of a patient with cirrhosis, or a patient with hepatocellular carcinoma, is over 80% 5-year survival. In the SECA trials and TRANSMET trial, if we do a good selection, I think we can get to 70% 5-year survival. But until we have more data, I think it’s a cautious measure to, as a field, try to use living donors and not compete with the rest of the list of patients who are already dying on the list for liver transplants.

Once we get more data, it’s going to be something that, in the transplant community, we may be able to use deceased donors. Especially deceased donors with maybe extended criteria that are not going to be used for other patients. We can do living-unrelated or living-related donations. Family members or also friends or neighbors or part of the community, even altruistic donors, can donate to a potential recipient. And that enables us to not only time the transplant in an adequate manner, because we’re able to transplant the patient early, but also time it so we can give the number of chemotherapy cycles that we want to give.

That’s a huge advantage. You don’t compete for a liver with the cadaveric waiting list of patients that are waiting for other reasons, and you can select the tumor biology very well because you know exactly when the surgery is going to be. For instance, we can say, okay, this patient has KRAS mutation, left-sided colon cancer, and has been having good tumor biology with no progression. We will wait 6 months from the primary tumor to the transplant, which is going to be 1 year from diagnosis to transplant. And we can see during that time whether they continue to have good tumor biology.

But if you have a deceased donor liver transplant, sometimes you can’t time that well and schedule it. It becomes a bit more tricky in terms of patient selection and making sure that we do this for the people who are going to benefit.

Dr. Schlechter: And how does donor matching work? Is it HLA (human leukocyte antigen) matched or ABO-matched? Who can donate when you say a living-related? For example, when we think about bone marrow transplantation, which we’re all familiar with in the oncology population, it’s an incredibly complex match process. Is this the same challenge?

Dr. Dib: No, it’s a little bit simpler. Living donors for liver transplants need to be between the ages of 18 and 60. They need to be relatively healthy, relatively fit, with a BMI hopefully less than 30, definitely less than 35. The compatibility is ABO compatibility. So, if they’re ABO-compatible, relatively young, relatively healthy, they would be a potential donor and we will go ahead and do a CT scan.

If the CT scan shows that they have a good, adequate anatomy, more than 90% of those will be good donors. I would say that out of 100 people who want to be donors, 25 of them will be adequate. One out of four people who want to save their family member and want to have this operation are able to donate half of their liver to their family member or loved one.

Dr. Schlechter: Excellent. And it’s helpful to know that the matching process is simpler. During his discussion, René Adam unequivocally stated that liver transplants are a new standard of care for colorectal cancer. And I guess my question is, do you agree with this statement? How do we balance the demand for living donors and the demand for deceased donors? Especially in a time of increasing fatty liver disease and obesity, other indications for liver transplant, causes of cirrhosis, and also in an era of young-onset colorectal cancer. Patients are younger. Is this a new standard of care? Do you agree with that statement?

Dr. Dib: I do agree with that statement. I think it’s important to understand that not all patients with colorectal mets are the same. Of the number of patients in the United States who have colorectal cancer, let’s say 50% of them will have liver metastasis. Only 15%-20% of them will have liver-only metastasis.

This is only for patients who have liver-only metastasis without extrahepatic disease. And only maybe 15%-20% of them will meet all the criteria to be able to undergo liver transplantation. I think it’s for a very selective subset of patients who have very good tumor biology, generally young patients who don’t have any other alternative to having even a complex liver resection and are not able to get R0 resection. That is when we could think about doing liver transplantation.

It’s one more of the skills that we can have. It doesn’t mean that it will be the only skill, or the best skill, for all of the patients.

Dr. Schlechter: When a patient volunteers to be a living donor for a loved one or a family member, and they go through all the screening and they’re found to be a candidate, what is the surgical experience for that patient?

How long are they in the hospital? What sort of operation is that?

Dr. Dib: Living donors are very special patients. These are patients who do not need an operation. And the only reason they’re doing this is to save the life of their loved one. Donor safety is our priority number one, two, three, and four. The donor operation needs to be perfect.

And so we take good care of, first of all, selecting the living donors, making sure that they’re young and they don’t have any big contraindications. We also ensure that they are well informed of the process. The living donor surgery that we’re now doing is laparoscopic and minimally invasive. Here at Beth Israel Deaconess, we have done it laparoscopically with very good results.

I think that experience before and after the surgery gets so much better because of the better recovery. They’re able to go home, in general, within 4 or 5 days, and they get on with their normal life within 6-8 weeks. I think it’s important for them to know all the processes and the actual risks and benefits for the recipient.

Among those risks, I think it’s important for them to understand that this is a complex operation. Even if we do it laparoscopically or robotically, so that the scar is less, inside we’re still taking out half of the liver. That is a surgery that needs to be undertaken very meticulously, with a focus on minimizing any bleeding.

It’s a surgery that takes a long time. It takes about 6 hours. We do our best to try to minimize any risks.

Dr. Schlechter: Excellent. Thanks for that. Today we had Dr. Martin Dib joining us to discuss liver transplant for metastatic colorectal cancer. We discussed the various important criteria. We discussed that early referral to multidisciplinary centers that manage these is important to help get patients set up.

We discussed the fact that there are certain inclusion and exclusion criteria to consider. Obviously, unresectable disease is a critical determination that should be made by a liver surgeon. The absence of extrahepatic disease is important in staging with PET or other imaging. We discussed certain other biological exclusions.

There’s a relative contraindication of right-sided vs left-sided cancers, but right-sided cancers can be transplanted. We discussed that an elevated CEA greater than 80 is a contraindication, as are mutations in BRAF. We reviewed data from both the TRANSMET trial recently published in The Lancet and presented at ASCO in 2024, as well as the older Oslo criteria and Oslo trials and SECA trials.

And finally, we heard that donors can now come as living donors, a laparoscopic robotic surgery with a better safety profile, and greater access to organs that are ABO matched and not HLA matched because of the nature of the biology. Thank you again for joining us.


 

Benjamin L. Schlechter, MD, is senior physician, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston, Massachusetts. He has disclosed no relevant financial relationships. Martin J. Dib, MD, is member of the faculty, Department of Surgery, Harvard Medical School; director of Hepatobiliary Surgery, Division of Transplantation, Beth Israel Deaconess Medical Center, Boston. He has disclosed no relevant financial relationships.

A version of this transcript appeared on Medscape.com.

This transcript has been edited for clarity.
 

Benjamin L. Schlechter, MD: Today we’re discussing liver transplant for metastatic colorectal cancer with our guest, Dr. Martin Dib. Dr. Dib is the director of the Hepatobiliary Surgery and Living Donor Program at Beth Israel Deaconess Medical Center here in Boston, and a Harvard Medical School faculty member.

He was previously at the Pontificia Universidad Católica de Chile, a leading international institution investigating the role of liver transplant in colorectal cancer, among other diseases. Dr. Dib, before we move to our discussion, I’d like to hear a bit about your pathway to becoming a transplant surgeon. How did you end up working on colorectal cancer and liver transplants in this field?

Martin J. Dib, MD: Thank you so much, Dr. Schlechter. I am originally from Chile. I had an opportunity to come to Beth Israel Deaconess Medical Center after medical school and I did liver regeneration research at the transplant center. After that, I was lucky enough to match as a general surgery resident at Beth Israel Deaconess.

This is my alma mater and I was able to graduate as a surgeon here. You and I had some paths together. After graduating from Harvard as a surgeon, I was trained in liver transplant, abdominal transplant, surgical oncology, and hepatobiliary surgery at the University of Toronto.

I have been developing this passion for being able to transplant cancer patients and use organ transplant techniques to be able to do complex resections for cancer.

Dr. Schlechter: Let’s talk about the topic for today, which is liver transplant and colorectal cancer. I’ll be honest — this is not a very familiar topic for a lot of oncologists. There are a lot of details that I think are new to us as oncologists. We need to expand this conversation to get access to patients for this.

First and foremost, can you talk about some of the parameters for a resectable liver metastasis vs unresectable disease that would be an indication for a liver transplant?

Dr. Dib: I think this is a very interesting topic because liver transplantation for cancer is not new. Liver transplantation started in the 1960s when people started doing liver transplants for advanced liver tumors. The problem is that they were selecting patients who had very advanced — and poor tumor biology — tumors. The outcomes were not good.

It was only in 1996 when the Milan criteria started. Mazzaferro and colleagues, using strict patient selection, were able to do liver transplant for selected hepatocellular carcinoma patients. Having those excellent outcomes in selecting patients opened the field for what we now call transplant oncology, which is using selection criteria and using other methods to be able to select which patients will do well after transplantation, even with immunosuppression.

Liver transplantation for colorectal metastasis was used at the very beginning of the era of liver transplantation, but with very poor outcomes. It was abandoned because of the outcomes. It is exciting to see that after 20 years of not doing it, there was a group in Norway that started again. They are doing liver transplants for colorectal metastases (mets), but with very selected patients.

In Norway, they had a very unusual setting where they had more liver donors than patients on the list waiting for liver transplant. So they can’t share these livers and we’re all jealous, right? Every single country in the West struggles because we don’t have enough livers for the rest of the list. And they had a lot of livers to be able to transplant people.

They decided to transplant some selected patients with colorectal mets that were unresectable. And the surprise was that they found that they were able to get a 60% survival at 5 years. And so that was new. After that, in Norway, they started showing this data to other centers in the world. It wasn’t until this year that we could see not only the long-term data and long-term outcomes of using liver transplantation for unresectable colorectal mets, but also we’re now having data from a prospective clinical trial from France.

It was three countries in the prospective clinical trial: France, Belgium, and Italy. We now see that we have a little stronger data to support the use of liver transplants for unresectable colorectal mets.

Dr. Schlechter: That’s the TRANSMET study you’re referencing that was presented at ASCO in the late-breaking abstract session in 2024, and then more recently in The Lancet’s eClinicalMedicine. Both of those papers were led by René Adam. That was a cool presentation to sit through. I was in the room, and I was taking a ton of notes and there was a lot of info that came out of that.

First of all, it showed that patients who had received chemotherapy and were responding could then go on to liver transplant in that population. Impressively, 81% of the patients who were randomized to transplant received it. Frankly, that’s a big number, especially compared with the West, as you said, and in particular the US and here in New England where livers are a very precious commodity.

And even accounting for that, if you look at the intention-to-treat analysis, the 5-year overall survival in that population was 57% compared with 13% with chemotherapy. And that feels like a real number for chemotherapy. If you look at the per-protocol analysis, frankly, the numbers are higher.

It’s always a challenging assessment. What was also interesting to me was the pattern of recurrence, which in general was that recurrences were extrahepatic. So not only were patients rendered disease-free, but in general, the liver remained disease-free and only 3% of patients had liver-only recurrence and 11% had widespread metastatic disease.

The biggest group was lung metastases, at about 40%. Ultimately, they reported a progression-free survival of 17. 4 months for transplant compared with 6. 4 months with chemotherapy. On every parameter, it looks like liver transplant wins for these people. Help me out. Who are these people? How do we find these people?

What are the inclusions and exclusions for this population?

Dr. Dib: I think that’s very important. This is not a therapy that will be for every patient. These are selected patients who have liver-only unresectable colorectal mets. These are patients that don’t have any extrahepatic disease and that either the primary has been taken out already or that they have the primary present, but the plan is to take the primary and then do a liver transplantation after 3 months, hopefully after 6 months, of removing the primary.

These are patients who meet all the criteria that we have seen in terms of the best outcomes — patients that have Oslo scores of less than three. The Oslo trial, which included the SECA (Secondary Cancer)-I and SECA-II trials, basically showed that patients with a maximal tumor diameter of less than 5.5 with a pretransplant CEA (carcinoembryonic antigen) of less than 80 that do not have progression on chemotherapy, among other variables, do better. But the concept is that this is a therapy that will apply only to selected patients. That way we can continue to have adequate overall survival post-transplant that would be comparable to other diseases that we do liver transplants for.

Dr. Schlechter: Were there other biomarkers, any mutations that were included or excluded?

Dr. Dib: Yes. If you look at SECA-I, SECA-II trial outcomes, and also TRANSMET, they all say patients with BRAF mutations shouldn’t be transplanted. There are other parameters, including, for example, the site of the primary tumor. Patients with a left-sided colon primary tumor do much better than patients who have a right-sided primary tumor.

That’s not a complete contraindication, but if you look at the most updated inclusion criteria of programs, like the ones that the one that we have here at Beth Israel Deaconess and many others, the inclusion criteria protocols include patients who have only hepatic disease.

So, if there are no extrahepatic mets, the resection of the primary has been done or will be done after a multidisciplinary discussion. We want to make sure they have the absence of BRAF mutation, and that they don’t have disease progression while on chemotherapy. So hopefully we have data from enough months to be able to make sure that there’s no intrahepatic or extrahepatic progression while on chemotherapy.

And that’s including CEA and also looking at the imaging.

Dr. Schlechter: When you’re seeing a patient, how much chemo do you think they should have? What’s a good run chemotherapy-wise for these patients? Let’s say, before I refer a patient to you, how much chemo should they have? And then what should I do? Do I get a PET scan? Do I get MRI? What’s the right scanning I should do to prove there’s no extrahepatic disease before sending a patient in for consideration?

Dr. Dib: First, we need to confirm unresectability. Referring patients early is always a good measure to make sure that we’re all in agreement that it’s an unresectable patient. Having a PET scan from the very beginning is helpful because it shows the disease before doing chemotherapy.

In terms of the lines of chemotherapy, ideally in the TRANSMET trial, for example, the idea was to show tumor control for at least 3 months, with less than three lines of chemotherapy. Some patients will do that with FOLFIRI. It depends on the case.

I think some of those evaluations will need a multidisciplinary discussion. In our case, we are connected to the Norway team. We frequently talk with the Oslo team and an international community of transplant centers to get opinions on particular cases.

But I think referring patients early is a good measure. If we don’t think that they qualify, we will let the team know. We’re strictly looking at patients who have unresectable liver mets that don’t have extrahepatic disease. The idea is to do a primary tumor resection, and then get to transplantation, hopefully after 6 months. In some cases that have some concerns in terms of tumor biology, we may even extend the time from diagnosis to transplant to over 1.5 years.

Dr. Schlechter: Excellent. And what’s the experience like for these patients? In training as a resident many years ago, I saw patients with cirrhosis who went on to have a liver transplant, and that was sort of trading one disease for another. What is the posttransplant, or the remission, experience of a liver transplant for colorectal cancer like for the patient?

Dr. Dib: That’s a very important point. I think that transplantation has gotten better and better, as has chemotherapy systemic therapy. The liver transplantation experience from 20 years ago has improved dramatically. I think the quality of life of liver transplant patients after transplantation has increased quite a bit.

At Beth Israel Deaconess, we have a liver transplant program that is doing over a 100 livers a year. And when you have a high-volume center, usually the experience gets better. The time in the hospital post-transplant decreases.

In general, when we’re doing liver transplants, patients are getting extubated in the OR 30% of the time. The vast majority of patients are going home within 1 or 2 weeks. They need to have immunosuppression for the rest of their lives. We have a very good program of transplant coordinators that will help the family and the patient to live with immunosuppression and live with a transplanted organ.

But I would say that we have many, many patients, especially these patients who are not patients with cirrhosis. Their health is not as deteriorated as patients who have low MELD (model for end-stage liver disease) scores. They don’t have liver disease. They have cancer. So usually patients like that, many of them can go back to work and live a quality of life that is fairly reasonable.

Dr. Schlechter: That’s good to hear. When we hear statements like liver transplant for colon cancer, a lot of us have this picture of a much sicker population, but it’s interesting and true that the colorectal cancer population as a candidate for liver transplant is a much healthier population than the population with cirrhosis.

Let’s talk about organs and donors. Largely in the TRANSMET study, for example, that was cadaveric donors. Those were not living donors and you’ve done a lot of work on living donors. If the answer in the United States, because of limited access to organs, is going to be living donors, who are those donors?

What is that like? How do you identify them?

Dr. Dib: There’s a lot of advantages to using living donors for these patients. In any type of patient that needs a liver transplant, cadaveric donors or deceased donors is the same concept. There are two types of deceased donors: the brain-dead donors and donors after cardiac death. Those are hard to come by.

We still have 15%-20% mortality on the waiting list in the United States. We’re already still struggling to get enough donors to transplant the patients that are on the list. Now, if you add a new indication, which is unresectable colorectal mets, we need to make sure that the outcomes are equivalent to the patients who are going to be transplanted for other reasons.

Right now, for example, the 5-year overall survival of a patient with cirrhosis, or a patient with hepatocellular carcinoma, is over 80% 5-year survival. In the SECA trials and TRANSMET trial, if we do a good selection, I think we can get to 70% 5-year survival. But until we have more data, I think it’s a cautious measure to, as a field, try to use living donors and not compete with the rest of the list of patients who are already dying on the list for liver transplants.

Once we get more data, it’s going to be something that, in the transplant community, we may be able to use deceased donors. Especially deceased donors with maybe extended criteria that are not going to be used for other patients. We can do living-unrelated or living-related donations. Family members or also friends or neighbors or part of the community, even altruistic donors, can donate to a potential recipient. And that enables us to not only time the transplant in an adequate manner, because we’re able to transplant the patient early, but also time it so we can give the number of chemotherapy cycles that we want to give.

That’s a huge advantage. You don’t compete for a liver with the cadaveric waiting list of patients that are waiting for other reasons, and you can select the tumor biology very well because you know exactly when the surgery is going to be. For instance, we can say, okay, this patient has KRAS mutation, left-sided colon cancer, and has been having good tumor biology with no progression. We will wait 6 months from the primary tumor to the transplant, which is going to be 1 year from diagnosis to transplant. And we can see during that time whether they continue to have good tumor biology.

But if you have a deceased donor liver transplant, sometimes you can’t time that well and schedule it. It becomes a bit more tricky in terms of patient selection and making sure that we do this for the people who are going to benefit.

Dr. Schlechter: And how does donor matching work? Is it HLA (human leukocyte antigen) matched or ABO-matched? Who can donate when you say a living-related? For example, when we think about bone marrow transplantation, which we’re all familiar with in the oncology population, it’s an incredibly complex match process. Is this the same challenge?

Dr. Dib: No, it’s a little bit simpler. Living donors for liver transplants need to be between the ages of 18 and 60. They need to be relatively healthy, relatively fit, with a BMI hopefully less than 30, definitely less than 35. The compatibility is ABO compatibility. So, if they’re ABO-compatible, relatively young, relatively healthy, they would be a potential donor and we will go ahead and do a CT scan.

If the CT scan shows that they have a good, adequate anatomy, more than 90% of those will be good donors. I would say that out of 100 people who want to be donors, 25 of them will be adequate. One out of four people who want to save their family member and want to have this operation are able to donate half of their liver to their family member or loved one.

Dr. Schlechter: Excellent. And it’s helpful to know that the matching process is simpler. During his discussion, René Adam unequivocally stated that liver transplants are a new standard of care for colorectal cancer. And I guess my question is, do you agree with this statement? How do we balance the demand for living donors and the demand for deceased donors? Especially in a time of increasing fatty liver disease and obesity, other indications for liver transplant, causes of cirrhosis, and also in an era of young-onset colorectal cancer. Patients are younger. Is this a new standard of care? Do you agree with that statement?

Dr. Dib: I do agree with that statement. I think it’s important to understand that not all patients with colorectal mets are the same. Of the number of patients in the United States who have colorectal cancer, let’s say 50% of them will have liver metastasis. Only 15%-20% of them will have liver-only metastasis.

This is only for patients who have liver-only metastasis without extrahepatic disease. And only maybe 15%-20% of them will meet all the criteria to be able to undergo liver transplantation. I think it’s for a very selective subset of patients who have very good tumor biology, generally young patients who don’t have any other alternative to having even a complex liver resection and are not able to get R0 resection. That is when we could think about doing liver transplantation.

It’s one more of the skills that we can have. It doesn’t mean that it will be the only skill, or the best skill, for all of the patients.

Dr. Schlechter: When a patient volunteers to be a living donor for a loved one or a family member, and they go through all the screening and they’re found to be a candidate, what is the surgical experience for that patient?

How long are they in the hospital? What sort of operation is that?

Dr. Dib: Living donors are very special patients. These are patients who do not need an operation. And the only reason they’re doing this is to save the life of their loved one. Donor safety is our priority number one, two, three, and four. The donor operation needs to be perfect.

And so we take good care of, first of all, selecting the living donors, making sure that they’re young and they don’t have any big contraindications. We also ensure that they are well informed of the process. The living donor surgery that we’re now doing is laparoscopic and minimally invasive. Here at Beth Israel Deaconess, we have done it laparoscopically with very good results.

I think that experience before and after the surgery gets so much better because of the better recovery. They’re able to go home, in general, within 4 or 5 days, and they get on with their normal life within 6-8 weeks. I think it’s important for them to know all the processes and the actual risks and benefits for the recipient.

Among those risks, I think it’s important for them to understand that this is a complex operation. Even if we do it laparoscopically or robotically, so that the scar is less, inside we’re still taking out half of the liver. That is a surgery that needs to be undertaken very meticulously, with a focus on minimizing any bleeding.

It’s a surgery that takes a long time. It takes about 6 hours. We do our best to try to minimize any risks.

Dr. Schlechter: Excellent. Thanks for that. Today we had Dr. Martin Dib joining us to discuss liver transplant for metastatic colorectal cancer. We discussed the various important criteria. We discussed that early referral to multidisciplinary centers that manage these is important to help get patients set up.

We discussed the fact that there are certain inclusion and exclusion criteria to consider. Obviously, unresectable disease is a critical determination that should be made by a liver surgeon. The absence of extrahepatic disease is important in staging with PET or other imaging. We discussed certain other biological exclusions.

There’s a relative contraindication of right-sided vs left-sided cancers, but right-sided cancers can be transplanted. We discussed that an elevated CEA greater than 80 is a contraindication, as are mutations in BRAF. We reviewed data from both the TRANSMET trial recently published in The Lancet and presented at ASCO in 2024, as well as the older Oslo criteria and Oslo trials and SECA trials.

And finally, we heard that donors can now come as living donors, a laparoscopic robotic surgery with a better safety profile, and greater access to organs that are ABO matched and not HLA matched because of the nature of the biology. Thank you again for joining us.


 

Benjamin L. Schlechter, MD, is senior physician, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston, Massachusetts. He has disclosed no relevant financial relationships. Martin J. Dib, MD, is member of the faculty, Department of Surgery, Harvard Medical School; director of Hepatobiliary Surgery, Division of Transplantation, Beth Israel Deaconess Medical Center, Boston. He has disclosed no relevant financial relationships.

A version of this transcript appeared on Medscape.com.

This transcript has been edited for clarity.
 

Benjamin L. Schlechter, MD: Today we’re discussing liver transplant for metastatic colorectal cancer with our guest, Dr. Martin Dib. Dr. Dib is the director of the Hepatobiliary Surgery and Living Donor Program at Beth Israel Deaconess Medical Center here in Boston, and a Harvard Medical School faculty member.

He was previously at the Pontificia Universidad Católica de Chile, a leading international institution investigating the role of liver transplant in colorectal cancer, among other diseases. Dr. Dib, before we move to our discussion, I’d like to hear a bit about your pathway to becoming a transplant surgeon. How did you end up working on colorectal cancer and liver transplants in this field?

Martin J. Dib, MD: Thank you so much, Dr. Schlechter. I am originally from Chile. I had an opportunity to come to Beth Israel Deaconess Medical Center after medical school and I did liver regeneration research at the transplant center. After that, I was lucky enough to match as a general surgery resident at Beth Israel Deaconess.

This is my alma mater and I was able to graduate as a surgeon here. You and I had some paths together. After graduating from Harvard as a surgeon, I was trained in liver transplant, abdominal transplant, surgical oncology, and hepatobiliary surgery at the University of Toronto.

I have been developing this passion for being able to transplant cancer patients and use organ transplant techniques to be able to do complex resections for cancer.

Dr. Schlechter: Let’s talk about the topic for today, which is liver transplant and colorectal cancer. I’ll be honest — this is not a very familiar topic for a lot of oncologists. There are a lot of details that I think are new to us as oncologists. We need to expand this conversation to get access to patients for this.

First and foremost, can you talk about some of the parameters for a resectable liver metastasis vs unresectable disease that would be an indication for a liver transplant?

Dr. Dib: I think this is a very interesting topic because liver transplantation for cancer is not new. Liver transplantation started in the 1960s when people started doing liver transplants for advanced liver tumors. The problem is that they were selecting patients who had very advanced — and poor tumor biology — tumors. The outcomes were not good.

It was only in 1996 when the Milan criteria started. Mazzaferro and colleagues, using strict patient selection, were able to do liver transplant for selected hepatocellular carcinoma patients. Having those excellent outcomes in selecting patients opened the field for what we now call transplant oncology, which is using selection criteria and using other methods to be able to select which patients will do well after transplantation, even with immunosuppression.

Liver transplantation for colorectal metastasis was used at the very beginning of the era of liver transplantation, but with very poor outcomes. It was abandoned because of the outcomes. It is exciting to see that after 20 years of not doing it, there was a group in Norway that started again. They are doing liver transplants for colorectal metastases (mets), but with very selected patients.

In Norway, they had a very unusual setting where they had more liver donors than patients on the list waiting for liver transplant. So they can’t share these livers and we’re all jealous, right? Every single country in the West struggles because we don’t have enough livers for the rest of the list. And they had a lot of livers to be able to transplant people.

They decided to transplant some selected patients with colorectal mets that were unresectable. And the surprise was that they found that they were able to get a 60% survival at 5 years. And so that was new. After that, in Norway, they started showing this data to other centers in the world. It wasn’t until this year that we could see not only the long-term data and long-term outcomes of using liver transplantation for unresectable colorectal mets, but also we’re now having data from a prospective clinical trial from France.

It was three countries in the prospective clinical trial: France, Belgium, and Italy. We now see that we have a little stronger data to support the use of liver transplants for unresectable colorectal mets.

Dr. Schlechter: That’s the TRANSMET study you’re referencing that was presented at ASCO in the late-breaking abstract session in 2024, and then more recently in The Lancet’s eClinicalMedicine. Both of those papers were led by René Adam. That was a cool presentation to sit through. I was in the room, and I was taking a ton of notes and there was a lot of info that came out of that.

First of all, it showed that patients who had received chemotherapy and were responding could then go on to liver transplant in that population. Impressively, 81% of the patients who were randomized to transplant received it. Frankly, that’s a big number, especially compared with the West, as you said, and in particular the US and here in New England where livers are a very precious commodity.

And even accounting for that, if you look at the intention-to-treat analysis, the 5-year overall survival in that population was 57% compared with 13% with chemotherapy. And that feels like a real number for chemotherapy. If you look at the per-protocol analysis, frankly, the numbers are higher.

It’s always a challenging assessment. What was also interesting to me was the pattern of recurrence, which in general was that recurrences were extrahepatic. So not only were patients rendered disease-free, but in general, the liver remained disease-free and only 3% of patients had liver-only recurrence and 11% had widespread metastatic disease.

The biggest group was lung metastases, at about 40%. Ultimately, they reported a progression-free survival of 17. 4 months for transplant compared with 6. 4 months with chemotherapy. On every parameter, it looks like liver transplant wins for these people. Help me out. Who are these people? How do we find these people?

What are the inclusions and exclusions for this population?

Dr. Dib: I think that’s very important. This is not a therapy that will be for every patient. These are selected patients who have liver-only unresectable colorectal mets. These are patients that don’t have any extrahepatic disease and that either the primary has been taken out already or that they have the primary present, but the plan is to take the primary and then do a liver transplantation after 3 months, hopefully after 6 months, of removing the primary.

These are patients who meet all the criteria that we have seen in terms of the best outcomes — patients that have Oslo scores of less than three. The Oslo trial, which included the SECA (Secondary Cancer)-I and SECA-II trials, basically showed that patients with a maximal tumor diameter of less than 5.5 with a pretransplant CEA (carcinoembryonic antigen) of less than 80 that do not have progression on chemotherapy, among other variables, do better. But the concept is that this is a therapy that will apply only to selected patients. That way we can continue to have adequate overall survival post-transplant that would be comparable to other diseases that we do liver transplants for.

Dr. Schlechter: Were there other biomarkers, any mutations that were included or excluded?

Dr. Dib: Yes. If you look at SECA-I, SECA-II trial outcomes, and also TRANSMET, they all say patients with BRAF mutations shouldn’t be transplanted. There are other parameters, including, for example, the site of the primary tumor. Patients with a left-sided colon primary tumor do much better than patients who have a right-sided primary tumor.

That’s not a complete contraindication, but if you look at the most updated inclusion criteria of programs, like the ones that the one that we have here at Beth Israel Deaconess and many others, the inclusion criteria protocols include patients who have only hepatic disease.

So, if there are no extrahepatic mets, the resection of the primary has been done or will be done after a multidisciplinary discussion. We want to make sure they have the absence of BRAF mutation, and that they don’t have disease progression while on chemotherapy. So hopefully we have data from enough months to be able to make sure that there’s no intrahepatic or extrahepatic progression while on chemotherapy.

And that’s including CEA and also looking at the imaging.

Dr. Schlechter: When you’re seeing a patient, how much chemo do you think they should have? What’s a good run chemotherapy-wise for these patients? Let’s say, before I refer a patient to you, how much chemo should they have? And then what should I do? Do I get a PET scan? Do I get MRI? What’s the right scanning I should do to prove there’s no extrahepatic disease before sending a patient in for consideration?

Dr. Dib: First, we need to confirm unresectability. Referring patients early is always a good measure to make sure that we’re all in agreement that it’s an unresectable patient. Having a PET scan from the very beginning is helpful because it shows the disease before doing chemotherapy.

In terms of the lines of chemotherapy, ideally in the TRANSMET trial, for example, the idea was to show tumor control for at least 3 months, with less than three lines of chemotherapy. Some patients will do that with FOLFIRI. It depends on the case.

I think some of those evaluations will need a multidisciplinary discussion. In our case, we are connected to the Norway team. We frequently talk with the Oslo team and an international community of transplant centers to get opinions on particular cases.

But I think referring patients early is a good measure. If we don’t think that they qualify, we will let the team know. We’re strictly looking at patients who have unresectable liver mets that don’t have extrahepatic disease. The idea is to do a primary tumor resection, and then get to transplantation, hopefully after 6 months. In some cases that have some concerns in terms of tumor biology, we may even extend the time from diagnosis to transplant to over 1.5 years.

Dr. Schlechter: Excellent. And what’s the experience like for these patients? In training as a resident many years ago, I saw patients with cirrhosis who went on to have a liver transplant, and that was sort of trading one disease for another. What is the posttransplant, or the remission, experience of a liver transplant for colorectal cancer like for the patient?

Dr. Dib: That’s a very important point. I think that transplantation has gotten better and better, as has chemotherapy systemic therapy. The liver transplantation experience from 20 years ago has improved dramatically. I think the quality of life of liver transplant patients after transplantation has increased quite a bit.

At Beth Israel Deaconess, we have a liver transplant program that is doing over a 100 livers a year. And when you have a high-volume center, usually the experience gets better. The time in the hospital post-transplant decreases.

In general, when we’re doing liver transplants, patients are getting extubated in the OR 30% of the time. The vast majority of patients are going home within 1 or 2 weeks. They need to have immunosuppression for the rest of their lives. We have a very good program of transplant coordinators that will help the family and the patient to live with immunosuppression and live with a transplanted organ.

But I would say that we have many, many patients, especially these patients who are not patients with cirrhosis. Their health is not as deteriorated as patients who have low MELD (model for end-stage liver disease) scores. They don’t have liver disease. They have cancer. So usually patients like that, many of them can go back to work and live a quality of life that is fairly reasonable.

Dr. Schlechter: That’s good to hear. When we hear statements like liver transplant for colon cancer, a lot of us have this picture of a much sicker population, but it’s interesting and true that the colorectal cancer population as a candidate for liver transplant is a much healthier population than the population with cirrhosis.

Let’s talk about organs and donors. Largely in the TRANSMET study, for example, that was cadaveric donors. Those were not living donors and you’ve done a lot of work on living donors. If the answer in the United States, because of limited access to organs, is going to be living donors, who are those donors?

What is that like? How do you identify them?

Dr. Dib: There’s a lot of advantages to using living donors for these patients. In any type of patient that needs a liver transplant, cadaveric donors or deceased donors is the same concept. There are two types of deceased donors: the brain-dead donors and donors after cardiac death. Those are hard to come by.

We still have 15%-20% mortality on the waiting list in the United States. We’re already still struggling to get enough donors to transplant the patients that are on the list. Now, if you add a new indication, which is unresectable colorectal mets, we need to make sure that the outcomes are equivalent to the patients who are going to be transplanted for other reasons.

Right now, for example, the 5-year overall survival of a patient with cirrhosis, or a patient with hepatocellular carcinoma, is over 80% 5-year survival. In the SECA trials and TRANSMET trial, if we do a good selection, I think we can get to 70% 5-year survival. But until we have more data, I think it’s a cautious measure to, as a field, try to use living donors and not compete with the rest of the list of patients who are already dying on the list for liver transplants.

Once we get more data, it’s going to be something that, in the transplant community, we may be able to use deceased donors. Especially deceased donors with maybe extended criteria that are not going to be used for other patients. We can do living-unrelated or living-related donations. Family members or also friends or neighbors or part of the community, even altruistic donors, can donate to a potential recipient. And that enables us to not only time the transplant in an adequate manner, because we’re able to transplant the patient early, but also time it so we can give the number of chemotherapy cycles that we want to give.

That’s a huge advantage. You don’t compete for a liver with the cadaveric waiting list of patients that are waiting for other reasons, and you can select the tumor biology very well because you know exactly when the surgery is going to be. For instance, we can say, okay, this patient has KRAS mutation, left-sided colon cancer, and has been having good tumor biology with no progression. We will wait 6 months from the primary tumor to the transplant, which is going to be 1 year from diagnosis to transplant. And we can see during that time whether they continue to have good tumor biology.

But if you have a deceased donor liver transplant, sometimes you can’t time that well and schedule it. It becomes a bit more tricky in terms of patient selection and making sure that we do this for the people who are going to benefit.

Dr. Schlechter: And how does donor matching work? Is it HLA (human leukocyte antigen) matched or ABO-matched? Who can donate when you say a living-related? For example, when we think about bone marrow transplantation, which we’re all familiar with in the oncology population, it’s an incredibly complex match process. Is this the same challenge?

Dr. Dib: No, it’s a little bit simpler. Living donors for liver transplants need to be between the ages of 18 and 60. They need to be relatively healthy, relatively fit, with a BMI hopefully less than 30, definitely less than 35. The compatibility is ABO compatibility. So, if they’re ABO-compatible, relatively young, relatively healthy, they would be a potential donor and we will go ahead and do a CT scan.

If the CT scan shows that they have a good, adequate anatomy, more than 90% of those will be good donors. I would say that out of 100 people who want to be donors, 25 of them will be adequate. One out of four people who want to save their family member and want to have this operation are able to donate half of their liver to their family member or loved one.

Dr. Schlechter: Excellent. And it’s helpful to know that the matching process is simpler. During his discussion, René Adam unequivocally stated that liver transplants are a new standard of care for colorectal cancer. And I guess my question is, do you agree with this statement? How do we balance the demand for living donors and the demand for deceased donors? Especially in a time of increasing fatty liver disease and obesity, other indications for liver transplant, causes of cirrhosis, and also in an era of young-onset colorectal cancer. Patients are younger. Is this a new standard of care? Do you agree with that statement?

Dr. Dib: I do agree with that statement. I think it’s important to understand that not all patients with colorectal mets are the same. Of the number of patients in the United States who have colorectal cancer, let’s say 50% of them will have liver metastasis. Only 15%-20% of them will have liver-only metastasis.

This is only for patients who have liver-only metastasis without extrahepatic disease. And only maybe 15%-20% of them will meet all the criteria to be able to undergo liver transplantation. I think it’s for a very selective subset of patients who have very good tumor biology, generally young patients who don’t have any other alternative to having even a complex liver resection and are not able to get R0 resection. That is when we could think about doing liver transplantation.

It’s one more of the skills that we can have. It doesn’t mean that it will be the only skill, or the best skill, for all of the patients.

Dr. Schlechter: When a patient volunteers to be a living donor for a loved one or a family member, and they go through all the screening and they’re found to be a candidate, what is the surgical experience for that patient?

How long are they in the hospital? What sort of operation is that?

Dr. Dib: Living donors are very special patients. These are patients who do not need an operation. And the only reason they’re doing this is to save the life of their loved one. Donor safety is our priority number one, two, three, and four. The donor operation needs to be perfect.

And so we take good care of, first of all, selecting the living donors, making sure that they’re young and they don’t have any big contraindications. We also ensure that they are well informed of the process. The living donor surgery that we’re now doing is laparoscopic and minimally invasive. Here at Beth Israel Deaconess, we have done it laparoscopically with very good results.

I think that experience before and after the surgery gets so much better because of the better recovery. They’re able to go home, in general, within 4 or 5 days, and they get on with their normal life within 6-8 weeks. I think it’s important for them to know all the processes and the actual risks and benefits for the recipient.

Among those risks, I think it’s important for them to understand that this is a complex operation. Even if we do it laparoscopically or robotically, so that the scar is less, inside we’re still taking out half of the liver. That is a surgery that needs to be undertaken very meticulously, with a focus on minimizing any bleeding.

It’s a surgery that takes a long time. It takes about 6 hours. We do our best to try to minimize any risks.

Dr. Schlechter: Excellent. Thanks for that. Today we had Dr. Martin Dib joining us to discuss liver transplant for metastatic colorectal cancer. We discussed the various important criteria. We discussed that early referral to multidisciplinary centers that manage these is important to help get patients set up.

We discussed the fact that there are certain inclusion and exclusion criteria to consider. Obviously, unresectable disease is a critical determination that should be made by a liver surgeon. The absence of extrahepatic disease is important in staging with PET or other imaging. We discussed certain other biological exclusions.

There’s a relative contraindication of right-sided vs left-sided cancers, but right-sided cancers can be transplanted. We discussed that an elevated CEA greater than 80 is a contraindication, as are mutations in BRAF. We reviewed data from both the TRANSMET trial recently published in The Lancet and presented at ASCO in 2024, as well as the older Oslo criteria and Oslo trials and SECA trials.

And finally, we heard that donors can now come as living donors, a laparoscopic robotic surgery with a better safety profile, and greater access to organs that are ABO matched and not HLA matched because of the nature of the biology. Thank you again for joining us.


 

Benjamin L. Schlechter, MD, is senior physician, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston, Massachusetts. He has disclosed no relevant financial relationships. Martin J. Dib, MD, is member of the faculty, Department of Surgery, Harvard Medical School; director of Hepatobiliary Surgery, Division of Transplantation, Beth Israel Deaconess Medical Center, Boston. He has disclosed no relevant financial relationships.

A version of this transcript appeared on Medscape.com.

TOPLINE:

A dietary pattern linked to the microbial signature of colorectal cancer (CRC) is positively correlated with an increased risk for CRC, particularly for tumors with detectable Fusobacterium nucleatum, the pks strain of Escherichia coli, and enterotoxigenic Bacteroides fragilis (ETBF).

METHODOLOGY:

• To date, no known studies have investigated how a dietary pattern (rather than just individual foods or nutrients) specifically directed at CRC-related microbes may contribute to an increased CRC risk.
• Using stool metagenomes and dietary information from 307 men and 212 women, researchers identified and then validated a dietary pattern specifically linked to an established CRC-related gut microbial signature, which they termed the CRC Microbial Dietary Score (CMDS).
• They then investigated the association between CMDS and the risk for CRC in 259,200 participants (50,637 men and 208,563 women) from three large US cohorts where health professionals provided detailed information on various lifestyle factors over long follow-up periods.
• Researchers also analyzed the risk for CRC on the basis of the presence of gut bacteria, such as F nucleatum, pks+ E coli, and ETBF, in the tumor tissues of the participants who underwent surgical resection for CRC.

TAKEAWAY:

• The CMDS was characterized by high intake of processed foods and low intake of fiber-rich foods.
• Over 6,467,378 person-years assessed in the three US cohorts, 3854 cases of incident CRC were documented, with 1172, 1096, and 1119 cases measured for F nucleatum, pks+ E coli, and ETBF, respectively.
• A higher CMDS was associated with an increased risk for CRC after adjusting for putative CRC risk factors (adjusted hazard ratio [HR], 1.25; P_trend < .001).
• The association between CMDS and the risk for CRC was stronger for tumors with detectable levels of F nucleatum (HR, 2.51; P_trend < .001), pks+ E coli (HR, 1.68; P_trend = .005), and ETBF (HR, 2.06; P_trend = .016).

IN PRACTICE:

“A dietary pattern with a low consumption of processed foods may help prevent colorectal cancer through modulation of the gut microbiome. The dietary pattern modulating the colorectal cancer–related gut microbial signature may particularly help prevent tumoral microbial positive colorectal cancer, which tends to have a worse prognosis,” the authors wrote.

SOURCE:

This study, led by Kai Wang and Chun-Han Lo, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, was published online in Gastroenterology.

LIMITATIONS:

The study’s observational design may have limited the ability to establish causality between dietary patterns and the risk for CRC. The inclusion of participants who were all health professionals from a predominantly White US population may have limited the generalizability of the findings to other populations. The reliance on self-reported dietary data may have introduced recall bias and affected the accuracy of the dietary pattern assessed.

DISCLOSURES:

This work was supported by various sources, including the National Institutes of Health and the Cancer Research UK Grand Challenge Award. One author served as a consultant for some pharmaceutical companies, and another received funding from various sources, both unrelated to this study.

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

TOPLINE:

A dietary pattern linked to the microbial signature of colorectal cancer (CRC) is positively correlated with an increased risk for CRC, particularly for tumors with detectable Fusobacterium nucleatum, the pks strain of Escherichia coli, and enterotoxigenic Bacteroides fragilis (ETBF).

METHODOLOGY:

• To date, no known studies have investigated how a dietary pattern (rather than just individual foods or nutrients) specifically directed at CRC-related microbes may contribute to an increased CRC risk.
• Using stool metagenomes and dietary information from 307 men and 212 women, researchers identified and then validated a dietary pattern specifically linked to an established CRC-related gut microbial signature, which they termed the CRC Microbial Dietary Score (CMDS).
• They then investigated the association between CMDS and the risk for CRC in 259,200 participants (50,637 men and 208,563 women) from three large US cohorts where health professionals provided detailed information on various lifestyle factors over long follow-up periods.
• Researchers also analyzed the risk for CRC on the basis of the presence of gut bacteria, such as F nucleatum, pks+ E coli, and ETBF, in the tumor tissues of the participants who underwent surgical resection for CRC.

TAKEAWAY:

• The CMDS was characterized by high intake of processed foods and low intake of fiber-rich foods.
• Over 6,467,378 person-years assessed in the three US cohorts, 3854 cases of incident CRC were documented, with 1172, 1096, and 1119 cases measured for F nucleatum, pks+ E coli, and ETBF, respectively.
• A higher CMDS was associated with an increased risk for CRC after adjusting for putative CRC risk factors (adjusted hazard ratio [HR], 1.25; P_trend < .001).
• The association between CMDS and the risk for CRC was stronger for tumors with detectable levels of F nucleatum (HR, 2.51; P_trend < .001), pks+ E coli (HR, 1.68; P_trend = .005), and ETBF (HR, 2.06; P_trend = .016).

IN PRACTICE:

“A dietary pattern with a low consumption of processed foods may help prevent colorectal cancer through modulation of the gut microbiome. The dietary pattern modulating the colorectal cancer–related gut microbial signature may particularly help prevent tumoral microbial positive colorectal cancer, which tends to have a worse prognosis,” the authors wrote.

SOURCE:

This study, led by Kai Wang and Chun-Han Lo, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, was published online in Gastroenterology.

LIMITATIONS:

The study’s observational design may have limited the ability to establish causality between dietary patterns and the risk for CRC. The inclusion of participants who were all health professionals from a predominantly White US population may have limited the generalizability of the findings to other populations. The reliance on self-reported dietary data may have introduced recall bias and affected the accuracy of the dietary pattern assessed.

DISCLOSURES:

This work was supported by various sources, including the National Institutes of Health and the Cancer Research UK Grand Challenge Award. One author served as a consultant for some pharmaceutical companies, and another received funding from various sources, both unrelated to this study.

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

TOPLINE:

A dietary pattern linked to the microbial signature of colorectal cancer (CRC) is positively correlated with an increased risk for CRC, particularly for tumors with detectable Fusobacterium nucleatum, the pks strain of Escherichia coli, and enterotoxigenic Bacteroides fragilis (ETBF).

METHODOLOGY:

• To date, no known studies have investigated how a dietary pattern (rather than just individual foods or nutrients) specifically directed at CRC-related microbes may contribute to an increased CRC risk.
• Using stool metagenomes and dietary information from 307 men and 212 women, researchers identified and then validated a dietary pattern specifically linked to an established CRC-related gut microbial signature, which they termed the CRC Microbial Dietary Score (CMDS).
• They then investigated the association between CMDS and the risk for CRC in 259,200 participants (50,637 men and 208,563 women) from three large US cohorts where health professionals provided detailed information on various lifestyle factors over long follow-up periods.
• Researchers also analyzed the risk for CRC on the basis of the presence of gut bacteria, such as F nucleatum, pks+ E coli, and ETBF, in the tumor tissues of the participants who underwent surgical resection for CRC.

TAKEAWAY:

• The CMDS was characterized by high intake of processed foods and low intake of fiber-rich foods.
• Over 6,467,378 person-years assessed in the three US cohorts, 3854 cases of incident CRC were documented, with 1172, 1096, and 1119 cases measured for F nucleatum, pks+ E coli, and ETBF, respectively.
• A higher CMDS was associated with an increased risk for CRC after adjusting for putative CRC risk factors (adjusted hazard ratio [HR], 1.25; P_trend < .001).
• The association between CMDS and the risk for CRC was stronger for tumors with detectable levels of F nucleatum (HR, 2.51; P_trend < .001), pks+ E coli (HR, 1.68; P_trend = .005), and ETBF (HR, 2.06; P_trend = .016).

IN PRACTICE:

“A dietary pattern with a low consumption of processed foods may help prevent colorectal cancer through modulation of the gut microbiome. The dietary pattern modulating the colorectal cancer–related gut microbial signature may particularly help prevent tumoral microbial positive colorectal cancer, which tends to have a worse prognosis,” the authors wrote.

SOURCE:

This study, led by Kai Wang and Chun-Han Lo, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, was published online in Gastroenterology.

LIMITATIONS:

The study’s observational design may have limited the ability to establish causality between dietary patterns and the risk for CRC. The inclusion of participants who were all health professionals from a predominantly White US population may have limited the generalizability of the findings to other populations. The reliance on self-reported dietary data may have introduced recall bias and affected the accuracy of the dietary pattern assessed.

DISCLOSURES:

This work was supported by various sources, including the National Institutes of Health and the Cancer Research UK Grand Challenge Award. One author served as a consultant for some pharmaceutical companies, and another received funding from various sources, both unrelated to this study.

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

TOPLINE:

Gastrointestinal stromal tumors (GISTs) have increased in incidence over the past 2 decades, with notable survival disparities among racial and ethnic groups, particularly among Black patients who face higher mortality rates from esophageal and gastric GISTs.

METHODOLOGY:

• A steep increase in GIST incidence was observed from 2000 to 2005, largely due to the reclassification of sarcomas as GISTs. The classification of GISTs has changed over time, with all GISTs now considered malignant instead of benign, likely further increasing the incidence. However, updated data on GIST trends are lacking.
• This study assessed recent trends in GIST incidence and survival outcomes across different racial and ethnic groups using data from the National Cancer Institute’s SEER database, including the SEER-22 and SEER-17 registries.
• Researchers evaluated annual percentage changes and incidences among 23,001 patients from SEER-22 (mean age, 64 years) and median overall and cancer-specific survival rates in 12,109 patients from SEER-17 (mean age, 64 years).
• More than half of the patients in both cohorts were White, 17.8%-19.6% were Black, 11.6%-12.3% were Hispanic, and 9.7%-13.2% were Asian or Pacific Islander.

TAKEAWAY:

• The rates of GISTs increased annually between 2000 and 2019 for all organ sites, except the colon, where it decreased by 0.2% per year. Esophageal GISTs increased by 7.3%, gastric by 5.1%, small intestine by 2.7%, and rectal by 1.9%.
• Black patients had significantly lower median overall survival than other racial groups. For example, the median survival for Black patients with esophageal GISTs was 3.6 years vs 15.3 years for White patients (hazard ratio [HR], 6.4; 95% CI, 2.0-20.3). Similar patterns were seen for gastric GISTs — 9.1 years for Black patients vs 11.8 years for White patients (HR, 1.4). GIST-specific mortality was also higher in Black patients for these two organ sites.
• Additionally, Asian or Pacific Islander patients with esophageal GISTs had lower survival rates, with a median of 8.8 years (HR, 5.6) vs 15.3 years for White patients. Similarly, American Indian or Alaska Native patients with gastric GIST had lower survival rates, with a median of 8.5 years (HR, 1.6) vs 11.8 years for White patients.
• Over the 20-year study period, 5-year relative survival rates improved for most patient groups but remained the lowest among American Indian or Alaska Native patients across various GIST sites.

IN PRACTICE:

“We observed a continued increase in the incidence of GISTs after 2005” with a “substantial increase in the last two decades,” the authors wrote. Therefore, “future research should explore lifestyle-related or environmental factors underlying the unfavorable trends” which “could not fully be explained by coding reclassification and advances in diagnostic technologies,” they further added.

SOURCE:

The study was led by Christian S. Alvarez, PhD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland. It was published online on August 19, 2024, in JAMA Network Open.

LIMITATIONS:

A lack of individual-level data on socioeconomic factors and healthcare access could have influenced the findings. Although the SEER registries used standardized codes and procedures for classifying the data on race and ethnicity, misclassification was possible. Additionally, data on prognostic factors were incomplete or missing, which limited the inferences of the analysis.

DISCLOSURES:

This work was supported by the National Institutes of Health Intramural Research Program of the National Cancer Institute. Two authors reported receiving grants or personal fees and having other ties with various sources.

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

TOPLINE:

Gastrointestinal stromal tumors (GISTs) have increased in incidence over the past 2 decades, with notable survival disparities among racial and ethnic groups, particularly among Black patients who face higher mortality rates from esophageal and gastric GISTs.

METHODOLOGY:

• A steep increase in GIST incidence was observed from 2000 to 2005, largely due to the reclassification of sarcomas as GISTs. The classification of GISTs has changed over time, with all GISTs now considered malignant instead of benign, likely further increasing the incidence. However, updated data on GIST trends are lacking.
• This study assessed recent trends in GIST incidence and survival outcomes across different racial and ethnic groups using data from the National Cancer Institute’s SEER database, including the SEER-22 and SEER-17 registries.
• Researchers evaluated annual percentage changes and incidences among 23,001 patients from SEER-22 (mean age, 64 years) and median overall and cancer-specific survival rates in 12,109 patients from SEER-17 (mean age, 64 years).
• More than half of the patients in both cohorts were White, 17.8%-19.6% were Black, 11.6%-12.3% were Hispanic, and 9.7%-13.2% were Asian or Pacific Islander.

TAKEAWAY:

• The rates of GISTs increased annually between 2000 and 2019 for all organ sites, except the colon, where it decreased by 0.2% per year. Esophageal GISTs increased by 7.3%, gastric by 5.1%, small intestine by 2.7%, and rectal by 1.9%.
• Black patients had significantly lower median overall survival than other racial groups. For example, the median survival for Black patients with esophageal GISTs was 3.6 years vs 15.3 years for White patients (hazard ratio [HR], 6.4; 95% CI, 2.0-20.3). Similar patterns were seen for gastric GISTs — 9.1 years for Black patients vs 11.8 years for White patients (HR, 1.4). GIST-specific mortality was also higher in Black patients for these two organ sites.
• Additionally, Asian or Pacific Islander patients with esophageal GISTs had lower survival rates, with a median of 8.8 years (HR, 5.6) vs 15.3 years for White patients. Similarly, American Indian or Alaska Native patients with gastric GIST had lower survival rates, with a median of 8.5 years (HR, 1.6) vs 11.8 years for White patients.
• Over the 20-year study period, 5-year relative survival rates improved for most patient groups but remained the lowest among American Indian or Alaska Native patients across various GIST sites.

IN PRACTICE:

“We observed a continued increase in the incidence of GISTs after 2005” with a “substantial increase in the last two decades,” the authors wrote. Therefore, “future research should explore lifestyle-related or environmental factors underlying the unfavorable trends” which “could not fully be explained by coding reclassification and advances in diagnostic technologies,” they further added.

SOURCE:

The study was led by Christian S. Alvarez, PhD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland. It was published online on August 19, 2024, in JAMA Network Open.

LIMITATIONS:

A lack of individual-level data on socioeconomic factors and healthcare access could have influenced the findings. Although the SEER registries used standardized codes and procedures for classifying the data on race and ethnicity, misclassification was possible. Additionally, data on prognostic factors were incomplete or missing, which limited the inferences of the analysis.

DISCLOSURES:

This work was supported by the National Institutes of Health Intramural Research Program of the National Cancer Institute. Two authors reported receiving grants or personal fees and having other ties with various sources.

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

TOPLINE:

Gastrointestinal stromal tumors (GISTs) have increased in incidence over the past 2 decades, with notable survival disparities among racial and ethnic groups, particularly among Black patients who face higher mortality rates from esophageal and gastric GISTs.

METHODOLOGY:

• A steep increase in GIST incidence was observed from 2000 to 2005, largely due to the reclassification of sarcomas as GISTs. The classification of GISTs has changed over time, with all GISTs now considered malignant instead of benign, likely further increasing the incidence. However, updated data on GIST trends are lacking.
• This study assessed recent trends in GIST incidence and survival outcomes across different racial and ethnic groups using data from the National Cancer Institute’s SEER database, including the SEER-22 and SEER-17 registries.
• Researchers evaluated annual percentage changes and incidences among 23,001 patients from SEER-22 (mean age, 64 years) and median overall and cancer-specific survival rates in 12,109 patients from SEER-17 (mean age, 64 years).
• More than half of the patients in both cohorts were White, 17.8%-19.6% were Black, 11.6%-12.3% were Hispanic, and 9.7%-13.2% were Asian or Pacific Islander.

TAKEAWAY:

• The rates of GISTs increased annually between 2000 and 2019 for all organ sites, except the colon, where it decreased by 0.2% per year. Esophageal GISTs increased by 7.3%, gastric by 5.1%, small intestine by 2.7%, and rectal by 1.9%.
• Black patients had significantly lower median overall survival than other racial groups. For example, the median survival for Black patients with esophageal GISTs was 3.6 years vs 15.3 years for White patients (hazard ratio [HR], 6.4; 95% CI, 2.0-20.3). Similar patterns were seen for gastric GISTs — 9.1 years for Black patients vs 11.8 years for White patients (HR, 1.4). GIST-specific mortality was also higher in Black patients for these two organ sites.
• Additionally, Asian or Pacific Islander patients with esophageal GISTs had lower survival rates, with a median of 8.8 years (HR, 5.6) vs 15.3 years for White patients. Similarly, American Indian or Alaska Native patients with gastric GIST had lower survival rates, with a median of 8.5 years (HR, 1.6) vs 11.8 years for White patients.
• Over the 20-year study period, 5-year relative survival rates improved for most patient groups but remained the lowest among American Indian or Alaska Native patients across various GIST sites.

IN PRACTICE:

“We observed a continued increase in the incidence of GISTs after 2005” with a “substantial increase in the last two decades,” the authors wrote. Therefore, “future research should explore lifestyle-related or environmental factors underlying the unfavorable trends” which “could not fully be explained by coding reclassification and advances in diagnostic technologies,” they further added.

SOURCE:

The study was led by Christian S. Alvarez, PhD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland. It was published online on August 19, 2024, in JAMA Network Open.

LIMITATIONS:

A lack of individual-level data on socioeconomic factors and healthcare access could have influenced the findings. Although the SEER registries used standardized codes and procedures for classifying the data on race and ethnicity, misclassification was possible. Additionally, data on prognostic factors were incomplete or missing, which limited the inferences of the analysis.

DISCLOSURES:

This work was supported by the National Institutes of Health Intramural Research Program of the National Cancer Institute. Two authors reported receiving grants or personal fees and having other ties with various sources.

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

TOPLINE:

Adjuvant everolimus does not improve recurrence-free or overall survival in patients with papillary and chromophobe subtypes of non–clear cell renal cell carcinoma (RCC) and is associated with higher rates of severe adverse events, compared with placebo.

METHODOLOGY:

• Non–clear cell RCC accounts for approximately 25% of RCC cases and includes various distinct tumor types such as papillary and chromophobe RCC. A common design flaw in clinical trials has been applying treatments effective in clear cell RCC to non–clear cell RCC subtypes without a strong biological rationale. The broad approval of drugs for RCC without considering subtype differences complicates treatment decisions.
• The EVEREST phase 3 randomized clinical trial evaluated everolimus in the adjuvant setting, enrolling patients with either clear cell (n = 1248) or non–clear cell (n = 208) RCC at high risk for recurrence after resection. The patients were randomly assigned to receive either everolimus or placebo.
• To assess the benefits of everolimus in patients with non–clear cell RCC, this analysis focused on the subgroup of 109 patients with papillary RCC (median age, 60 years) and 99 patients with chromophobe RCC (median age, 51 years).
• The primary outcome was recurrence-free survival, and the secondary outcome was overall survival. The median follow-up was 76 months.

TAKEAWAY:

• In the papillary RCC subgroup, the 5-year recurrence-free survival was lower among patients receiving everolimus vs placebo (62% vs 70%), but this difference was not significant (hazard ratio [HR], 1.19; 95% CI, 0.61-2.33; P = .61).
• In the chromophobe RCC subgroup, the 5-year recurrence-free survival was similar between the two groups — 79% for everolimus vs 77% for placebo (HR, 0.89; 95% CI, 0.37-2.13; P = .79).
• Everolimus was also not associated with a significant overall survival benefit in patients with papillary RCC (HR, 1.47; 95% CI, 0.67-3.24; P = .34) or chromophobe RCC (HR, 0.93; 95% CI, 0.33-2.65; P = .89). In the papillary RCC subgroup, 5-year overall survival rates were slightly lower in the everolimus group than in the placebo group (76% vs 82%); however, in the chromophobe RCC subgroup, the rates were the same for both arms (89%).
• Patients treated with everolimus reported an increased incidence of grade 3 or higher adverse events, compared with those treated with placebo (48% vs 9%). No treatment-related deaths were reported, but a significant number of patients — 54% with papillary RCC and 51% with chromophobe RCC — discontinued treatment early because of adverse events.

IN PRACTICE:

This secondary analysis “found that patients with papillary or chromophobe RCC did not benefit from treatment with everolimus in the adjuvant setting,” the authors wrote. “Our study highlights an area of unmet need in the kidney cancer field. It thus serves to provide a foundational background for future randomized clinical trials to address specific subgroups of RCC for risk mitigation strategies in the adjuvant setting.”

SOURCE:

The study was led by Shuchi Gulati, MD, MSc, University of California Davis Comprehensive Cancer Center, Sacramento, and was published online on August 6, 2024, in JAMA Network Open, along with an accompanying editorial.

LIMITATIONS:

The subgroup analyses were underpowered to detect a significant difference. Additionally, the study lacked a central pathology review to confirm non–clear cell histologies.

DISCLOSURES:

The study was supported by awards from the National Institutes of Health, National Cancer Institute, and National Clinical Trials Network. Several authors reported receiving grants or personal fees from various sources outside the submitted work.

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

TOPLINE:

Adjuvant everolimus does not improve recurrence-free or overall survival in patients with papillary and chromophobe subtypes of non–clear cell renal cell carcinoma (RCC) and is associated with higher rates of severe adverse events, compared with placebo.

METHODOLOGY:

• Non–clear cell RCC accounts for approximately 25% of RCC cases and includes various distinct tumor types such as papillary and chromophobe RCC. A common design flaw in clinical trials has been applying treatments effective in clear cell RCC to non–clear cell RCC subtypes without a strong biological rationale. The broad approval of drugs for RCC without considering subtype differences complicates treatment decisions.
• The EVEREST phase 3 randomized clinical trial evaluated everolimus in the adjuvant setting, enrolling patients with either clear cell (n = 1248) or non–clear cell (n = 208) RCC at high risk for recurrence after resection. The patients were randomly assigned to receive either everolimus or placebo.
• To assess the benefits of everolimus in patients with non–clear cell RCC, this analysis focused on the subgroup of 109 patients with papillary RCC (median age, 60 years) and 99 patients with chromophobe RCC (median age, 51 years).
• The primary outcome was recurrence-free survival, and the secondary outcome was overall survival. The median follow-up was 76 months.

TAKEAWAY:

• In the papillary RCC subgroup, the 5-year recurrence-free survival was lower among patients receiving everolimus vs placebo (62% vs 70%), but this difference was not significant (hazard ratio [HR], 1.19; 95% CI, 0.61-2.33; P = .61).
• In the chromophobe RCC subgroup, the 5-year recurrence-free survival was similar between the two groups — 79% for everolimus vs 77% for placebo (HR, 0.89; 95% CI, 0.37-2.13; P = .79).
• Everolimus was also not associated with a significant overall survival benefit in patients with papillary RCC (HR, 1.47; 95% CI, 0.67-3.24; P = .34) or chromophobe RCC (HR, 0.93; 95% CI, 0.33-2.65; P = .89). In the papillary RCC subgroup, 5-year overall survival rates were slightly lower in the everolimus group than in the placebo group (76% vs 82%); however, in the chromophobe RCC subgroup, the rates were the same for both arms (89%).
• Patients treated with everolimus reported an increased incidence of grade 3 or higher adverse events, compared with those treated with placebo (48% vs 9%). No treatment-related deaths were reported, but a significant number of patients — 54% with papillary RCC and 51% with chromophobe RCC — discontinued treatment early because of adverse events.

IN PRACTICE:

This secondary analysis “found that patients with papillary or chromophobe RCC did not benefit from treatment with everolimus in the adjuvant setting,” the authors wrote. “Our study highlights an area of unmet need in the kidney cancer field. It thus serves to provide a foundational background for future randomized clinical trials to address specific subgroups of RCC for risk mitigation strategies in the adjuvant setting.”

SOURCE:

The study was led by Shuchi Gulati, MD, MSc, University of California Davis Comprehensive Cancer Center, Sacramento, and was published online on August 6, 2024, in JAMA Network Open, along with an accompanying editorial.

LIMITATIONS:

The subgroup analyses were underpowered to detect a significant difference. Additionally, the study lacked a central pathology review to confirm non–clear cell histologies.

DISCLOSURES:

The study was supported by awards from the National Institutes of Health, National Cancer Institute, and National Clinical Trials Network. Several authors reported receiving grants or personal fees from various sources outside the submitted work.

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

TOPLINE:

Adjuvant everolimus does not improve recurrence-free or overall survival in patients with papillary and chromophobe subtypes of non–clear cell renal cell carcinoma (RCC) and is associated with higher rates of severe adverse events, compared with placebo.

METHODOLOGY:

• Non–clear cell RCC accounts for approximately 25% of RCC cases and includes various distinct tumor types such as papillary and chromophobe RCC. A common design flaw in clinical trials has been applying treatments effective in clear cell RCC to non–clear cell RCC subtypes without a strong biological rationale. The broad approval of drugs for RCC without considering subtype differences complicates treatment decisions.
• The EVEREST phase 3 randomized clinical trial evaluated everolimus in the adjuvant setting, enrolling patients with either clear cell (n = 1248) or non–clear cell (n = 208) RCC at high risk for recurrence after resection. The patients were randomly assigned to receive either everolimus or placebo.
• To assess the benefits of everolimus in patients with non–clear cell RCC, this analysis focused on the subgroup of 109 patients with papillary RCC (median age, 60 years) and 99 patients with chromophobe RCC (median age, 51 years).
• The primary outcome was recurrence-free survival, and the secondary outcome was overall survival. The median follow-up was 76 months.

TAKEAWAY:

• In the papillary RCC subgroup, the 5-year recurrence-free survival was lower among patients receiving everolimus vs placebo (62% vs 70%), but this difference was not significant (hazard ratio [HR], 1.19; 95% CI, 0.61-2.33; P = .61).
• In the chromophobe RCC subgroup, the 5-year recurrence-free survival was similar between the two groups — 79% for everolimus vs 77% for placebo (HR, 0.89; 95% CI, 0.37-2.13; P = .79).
• Everolimus was also not associated with a significant overall survival benefit in patients with papillary RCC (HR, 1.47; 95% CI, 0.67-3.24; P = .34) or chromophobe RCC (HR, 0.93; 95% CI, 0.33-2.65; P = .89). In the papillary RCC subgroup, 5-year overall survival rates were slightly lower in the everolimus group than in the placebo group (76% vs 82%); however, in the chromophobe RCC subgroup, the rates were the same for both arms (89%).
• Patients treated with everolimus reported an increased incidence of grade 3 or higher adverse events, compared with those treated with placebo (48% vs 9%). No treatment-related deaths were reported, but a significant number of patients — 54% with papillary RCC and 51% with chromophobe RCC — discontinued treatment early because of adverse events.

IN PRACTICE:

This secondary analysis “found that patients with papillary or chromophobe RCC did not benefit from treatment with everolimus in the adjuvant setting,” the authors wrote. “Our study highlights an area of unmet need in the kidney cancer field. It thus serves to provide a foundational background for future randomized clinical trials to address specific subgroups of RCC for risk mitigation strategies in the adjuvant setting.”

SOURCE:

The study was led by Shuchi Gulati, MD, MSc, University of California Davis Comprehensive Cancer Center, Sacramento, and was published online on August 6, 2024, in JAMA Network Open, along with an accompanying editorial.

LIMITATIONS:

The subgroup analyses were underpowered to detect a significant difference. Additionally, the study lacked a central pathology review to confirm non–clear cell histologies.

DISCLOSURES:

The study was supported by awards from the National Institutes of Health, National Cancer Institute, and National Clinical Trials Network. Several authors reported receiving grants or personal fees from various sources outside the submitted work.

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

TOPLINE:

In patients with pulmonary oligometastases from colorectal cancer (CRC), both stereotactic body radiotherapy (SBRT) and surgery led to similar overall survival rates at 5 years. However, those who received surgery had significantly better progression-free and disease-free survival rates, as well as a longer time to intrathoracic progression.
 

METHODOLOGY:

• SBRT has been shown to provide effective local control and improve short-term survival for patients with pulmonary oligometastases from CRC and has become an alternative for these patients who are ineligible or reluctant to undergo surgery. It’s unclear, however, whether SBRT should be prioritized over surgery in patients with CRC pulmonary metastases, largely because of a lack of prospective data.
• In the current analysis, researchers compared outcomes among 335 patients (median age, 61 years) with lung metastases from CRC who underwent surgery or SBRT, using data from the Peking University Cancer Hospital and Institute between March 2011 and September 2022.
• A total of 251 patients were included in the final analysis after propensity score matching, 173 (68.9%) underwent surgery and 78 (31.1%) received SBRT. The median follow-up was 61.6 months in the surgery group and 54.4 months in the SBRT group.
• The study outcomes were freedom from intrathoracic progression, progression-free survival, and overall survival.

TAKEAWAY:

• At 5 years, rates of freedom from intrathoracic progression were more than twofold higher in the surgery group than in the SBRT group (53% vs 23.4%; hazard ratio [HR], 0.46; P < .001). Progression-free survival rates were also more than twofold higher in the surgery group vs the SBRT group (43.8% vs 18.5%; HR, 0.47; P < .001), respectively. In the SBRT group, a higher percentage of patients had a disease-free interval of less than 12 months compared with the surgery group, with rates of 48.7% and 32.9%, respectively (P = 0.025). 
• Overall survival, however, was not significantly different between the two groups at 5 years (72.5% in the surgery group vs 63.7% in the SBRT group; P = .260). The number of pulmonary metastases (HR, 1.87; 95% CI, 1.11-3.14, P = .019 and tumor size (HR, 1.03; 95% CI, 1.00-1.05, P = .023) were significant prognostic factors for overall survival.
• Local recurrence was more prevalent after SBRT (33.3%) than surgery (16.9%), while new intrathoracic tumors occurred more frequently after surgery than SBRT (71.8% vs 43.1%). Repeated local treatments were common among patients with intrathoracic progression, which might have contributed to favorable survival outcomes in both groups.
• Both treatments were well-tolerated with no treatment-related mortality or grade ≥ 3 toxicities. In the surgery group, 14 patients experienced complications, including atrial fibrillation (n = 4) and prolonged air leaks (n = 7). In the SBRT group, radiation pneumonitis was the most common adverse event (n = 21).

IN PRACTICE:

SBRT yielded overall survival benefits similar to surgery despite a “higher likelihood of prior extrapulmonary metastases, a shorter disease-free interval, and a greater number of metastatic lesions,” the authors wrote. Still, SBRT should be regarded as an “effective alternative in cases in which surgical intervention is either unviable or declined by the patient,” the authors concluded.
 

SOURCE:

The study was co-led by Yaqi Wang and Xin Dong, Peking University Cancer Hospital & Institute, Beijing, China, and was published online in the International Journal of Radiation Oncology, Biology, Physics.
 

LIMITATIONS:

This single-center retrospective study had an inherent selection bias. The lack of balanced sample sizes of the surgery and SBRT groups might have affected the robustness of the statistical analyses. Detailed data on adverse events were not available.
 

DISCLOSURES:

The study was supported by grants from the National Natural Science Foundation of China, Beijing Natural Science Foundation, and Beijing Municipal Administration of Hospital’s Ascent Plan. The authors did not declare any conflicts of interest.

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

TOPLINE:

In patients with pulmonary oligometastases from colorectal cancer (CRC), both stereotactic body radiotherapy (SBRT) and surgery led to similar overall survival rates at 5 years. However, those who received surgery had significantly better progression-free and disease-free survival rates, as well as a longer time to intrathoracic progression.
 

METHODOLOGY:

• SBRT has been shown to provide effective local control and improve short-term survival for patients with pulmonary oligometastases from CRC and has become an alternative for these patients who are ineligible or reluctant to undergo surgery. It’s unclear, however, whether SBRT should be prioritized over surgery in patients with CRC pulmonary metastases, largely because of a lack of prospective data.
• In the current analysis, researchers compared outcomes among 335 patients (median age, 61 years) with lung metastases from CRC who underwent surgery or SBRT, using data from the Peking University Cancer Hospital and Institute between March 2011 and September 2022.
• A total of 251 patients were included in the final analysis after propensity score matching, 173 (68.9%) underwent surgery and 78 (31.1%) received SBRT. The median follow-up was 61.6 months in the surgery group and 54.4 months in the SBRT group.
• The study outcomes were freedom from intrathoracic progression, progression-free survival, and overall survival.

TAKEAWAY:

• At 5 years, rates of freedom from intrathoracic progression were more than twofold higher in the surgery group than in the SBRT group (53% vs 23.4%; hazard ratio [HR], 0.46; P < .001). Progression-free survival rates were also more than twofold higher in the surgery group vs the SBRT group (43.8% vs 18.5%; HR, 0.47; P < .001), respectively. In the SBRT group, a higher percentage of patients had a disease-free interval of less than 12 months compared with the surgery group, with rates of 48.7% and 32.9%, respectively (P = 0.025). 
• Overall survival, however, was not significantly different between the two groups at 5 years (72.5% in the surgery group vs 63.7% in the SBRT group; P = .260). The number of pulmonary metastases (HR, 1.87; 95% CI, 1.11-3.14, P = .019 and tumor size (HR, 1.03; 95% CI, 1.00-1.05, P = .023) were significant prognostic factors for overall survival.
• Local recurrence was more prevalent after SBRT (33.3%) than surgery (16.9%), while new intrathoracic tumors occurred more frequently after surgery than SBRT (71.8% vs 43.1%). Repeated local treatments were common among patients with intrathoracic progression, which might have contributed to favorable survival outcomes in both groups.
• Both treatments were well-tolerated with no treatment-related mortality or grade ≥ 3 toxicities. In the surgery group, 14 patients experienced complications, including atrial fibrillation (n = 4) and prolonged air leaks (n = 7). In the SBRT group, radiation pneumonitis was the most common adverse event (n = 21).

IN PRACTICE:

SBRT yielded overall survival benefits similar to surgery despite a “higher likelihood of prior extrapulmonary metastases, a shorter disease-free interval, and a greater number of metastatic lesions,” the authors wrote. Still, SBRT should be regarded as an “effective alternative in cases in which surgical intervention is either unviable or declined by the patient,” the authors concluded.
 

SOURCE:

The study was co-led by Yaqi Wang and Xin Dong, Peking University Cancer Hospital & Institute, Beijing, China, and was published online in the International Journal of Radiation Oncology, Biology, Physics.
 

LIMITATIONS:

This single-center retrospective study had an inherent selection bias. The lack of balanced sample sizes of the surgery and SBRT groups might have affected the robustness of the statistical analyses. Detailed data on adverse events were not available.
 

DISCLOSURES:

The study was supported by grants from the National Natural Science Foundation of China, Beijing Natural Science Foundation, and Beijing Municipal Administration of Hospital’s Ascent Plan. The authors did not declare any conflicts of interest.

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

TOPLINE:

In patients with pulmonary oligometastases from colorectal cancer (CRC), both stereotactic body radiotherapy (SBRT) and surgery led to similar overall survival rates at 5 years. However, those who received surgery had significantly better progression-free and disease-free survival rates, as well as a longer time to intrathoracic progression.
 

METHODOLOGY:

• SBRT has been shown to provide effective local control and improve short-term survival for patients with pulmonary oligometastases from CRC and has become an alternative for these patients who are ineligible or reluctant to undergo surgery. It’s unclear, however, whether SBRT should be prioritized over surgery in patients with CRC pulmonary metastases, largely because of a lack of prospective data.
• In the current analysis, researchers compared outcomes among 335 patients (median age, 61 years) with lung metastases from CRC who underwent surgery or SBRT, using data from the Peking University Cancer Hospital and Institute between March 2011 and September 2022.
• A total of 251 patients were included in the final analysis after propensity score matching, 173 (68.9%) underwent surgery and 78 (31.1%) received SBRT. The median follow-up was 61.6 months in the surgery group and 54.4 months in the SBRT group.
• The study outcomes were freedom from intrathoracic progression, progression-free survival, and overall survival.

TAKEAWAY:

• At 5 years, rates of freedom from intrathoracic progression were more than twofold higher in the surgery group than in the SBRT group (53% vs 23.4%; hazard ratio [HR], 0.46; P < .001). Progression-free survival rates were also more than twofold higher in the surgery group vs the SBRT group (43.8% vs 18.5%; HR, 0.47; P < .001), respectively. In the SBRT group, a higher percentage of patients had a disease-free interval of less than 12 months compared with the surgery group, with rates of 48.7% and 32.9%, respectively (P = 0.025). 
• Overall survival, however, was not significantly different between the two groups at 5 years (72.5% in the surgery group vs 63.7% in the SBRT group; P = .260). The number of pulmonary metastases (HR, 1.87; 95% CI, 1.11-3.14, P = .019 and tumor size (HR, 1.03; 95% CI, 1.00-1.05, P = .023) were significant prognostic factors for overall survival.
• Local recurrence was more prevalent after SBRT (33.3%) than surgery (16.9%), while new intrathoracic tumors occurred more frequently after surgery than SBRT (71.8% vs 43.1%). Repeated local treatments were common among patients with intrathoracic progression, which might have contributed to favorable survival outcomes in both groups.
• Both treatments were well-tolerated with no treatment-related mortality or grade ≥ 3 toxicities. In the surgery group, 14 patients experienced complications, including atrial fibrillation (n = 4) and prolonged air leaks (n = 7). In the SBRT group, radiation pneumonitis was the most common adverse event (n = 21).

IN PRACTICE:

SBRT yielded overall survival benefits similar to surgery despite a “higher likelihood of prior extrapulmonary metastases, a shorter disease-free interval, and a greater number of metastatic lesions,” the authors wrote. Still, SBRT should be regarded as an “effective alternative in cases in which surgical intervention is either unviable or declined by the patient,” the authors concluded.
 

SOURCE:

The study was co-led by Yaqi Wang and Xin Dong, Peking University Cancer Hospital & Institute, Beijing, China, and was published online in the International Journal of Radiation Oncology, Biology, Physics.
 

LIMITATIONS:

This single-center retrospective study had an inherent selection bias. The lack of balanced sample sizes of the surgery and SBRT groups might have affected the robustness of the statistical analyses. Detailed data on adverse events were not available.
 

DISCLOSURES:

The study was supported by grants from the National Natural Science Foundation of China, Beijing Natural Science Foundation, and Beijing Municipal Administration of Hospital’s Ascent Plan. The authors did not declare any conflicts of interest.

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

TOPLINE:

Aspirin provides greater protection against colorectal cancer (CRC) in people with unhealthy lifestyles, particularly smokers with higher body weight, new data suggest. 

METHODOLOGY:

• Aspirin is an established agent for CRC prevention. Whether individuals with more lifestyle risk factors might derive greater benefit from aspirin remains unclear.
• Researchers analyzed regular aspirin use (defined as taking two or more standard 325-mg tablets per week) using long-term follow-up data from 63,957 women in the Nurses’ Health Study and 43,698 men in the Health Professionals Follow-Up Study.
• They calculated a healthy lifestyle score for each participant based on body mass index (BMI), alcohol intake, physical activity, diet, and smoking, with higher scores corresponding to healthier lifestyles.
• Outcomes included multivariable-adjusted 10-year cumulative incidence of CRC, the absolute risk reduction (ARR) with aspirin use, and number needed to treat associated with regular aspirin use by lifestyle score.

TAKEAWAY:

• During more than 3 million person-years of follow-up, 2544 new cases of CRC were documented.
• The 10-year cumulative incidence of CRC was 1.98% among regular aspirin users compared with 2.95% among nonusers, corresponding to an ARR of 0.97%.
• The ARR associated with aspirin use was greatest among individuals with the unhealthiest lifestyle scores and progressively decreased with healthier lifestyle scores (P < .001 for additive interaction).
• Those with the unhealthiest lifestyle scores (0-1) had a 10-year ARR of 1.28% from aspirin use, whereas those with the healthiest lifestyle scores (4-5) had an ARR of 0.11%.
• The number needed to treat with aspirin for 10 years to prevent one CRC case was 78 for those with the unhealthiest lifestyles, compared with 909 for those with the healthiest lifestyles.
• Among the individual components of the healthy lifestyle score, higher BMI and smoking correlated with greater reductions in CRC risk from aspirin use.

IN PRACTICE:

“These results support the use of lifestyle risk factors to identify individuals who may have a more favorable risk-benefit profile for cancer prevention with aspirin,” the authors wrote. 

SOURCE:

The study, with first author Daniel R. Sikavi, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study population consisted of health professionals who were predominantly White, which may limit generalizability of the findings. Lifestyle factors and aspirin use were self-reported, which may introduce measurement errors. The study did not systematically assess adverse outcomes potentially due to aspirin use or the presence of a known hereditary cancer syndrome. 

DISCLOSURES:

The study had no commercial funding. The authors had no relevant conflicts of interest.

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

TOPLINE:

Aspirin provides greater protection against colorectal cancer (CRC) in people with unhealthy lifestyles, particularly smokers with higher body weight, new data suggest. 

METHODOLOGY:

• Aspirin is an established agent for CRC prevention. Whether individuals with more lifestyle risk factors might derive greater benefit from aspirin remains unclear.
• Researchers analyzed regular aspirin use (defined as taking two or more standard 325-mg tablets per week) using long-term follow-up data from 63,957 women in the Nurses’ Health Study and 43,698 men in the Health Professionals Follow-Up Study.
• They calculated a healthy lifestyle score for each participant based on body mass index (BMI), alcohol intake, physical activity, diet, and smoking, with higher scores corresponding to healthier lifestyles.
• Outcomes included multivariable-adjusted 10-year cumulative incidence of CRC, the absolute risk reduction (ARR) with aspirin use, and number needed to treat associated with regular aspirin use by lifestyle score.

TAKEAWAY:

• During more than 3 million person-years of follow-up, 2544 new cases of CRC were documented.
• The 10-year cumulative incidence of CRC was 1.98% among regular aspirin users compared with 2.95% among nonusers, corresponding to an ARR of 0.97%.
• The ARR associated with aspirin use was greatest among individuals with the unhealthiest lifestyle scores and progressively decreased with healthier lifestyle scores (P < .001 for additive interaction).
• Those with the unhealthiest lifestyle scores (0-1) had a 10-year ARR of 1.28% from aspirin use, whereas those with the healthiest lifestyle scores (4-5) had an ARR of 0.11%.
• The number needed to treat with aspirin for 10 years to prevent one CRC case was 78 for those with the unhealthiest lifestyles, compared with 909 for those with the healthiest lifestyles.
• Among the individual components of the healthy lifestyle score, higher BMI and smoking correlated with greater reductions in CRC risk from aspirin use.

IN PRACTICE:

“These results support the use of lifestyle risk factors to identify individuals who may have a more favorable risk-benefit profile for cancer prevention with aspirin,” the authors wrote. 

SOURCE:

The study, with first author Daniel R. Sikavi, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study population consisted of health professionals who were predominantly White, which may limit generalizability of the findings. Lifestyle factors and aspirin use were self-reported, which may introduce measurement errors. The study did not systematically assess adverse outcomes potentially due to aspirin use or the presence of a known hereditary cancer syndrome. 

DISCLOSURES:

The study had no commercial funding. The authors had no relevant conflicts of interest.

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

TOPLINE:

Aspirin provides greater protection against colorectal cancer (CRC) in people with unhealthy lifestyles, particularly smokers with higher body weight, new data suggest. 

METHODOLOGY:

• Aspirin is an established agent for CRC prevention. Whether individuals with more lifestyle risk factors might derive greater benefit from aspirin remains unclear.
• Researchers analyzed regular aspirin use (defined as taking two or more standard 325-mg tablets per week) using long-term follow-up data from 63,957 women in the Nurses’ Health Study and 43,698 men in the Health Professionals Follow-Up Study.
• They calculated a healthy lifestyle score for each participant based on body mass index (BMI), alcohol intake, physical activity, diet, and smoking, with higher scores corresponding to healthier lifestyles.
• Outcomes included multivariable-adjusted 10-year cumulative incidence of CRC, the absolute risk reduction (ARR) with aspirin use, and number needed to treat associated with regular aspirin use by lifestyle score.

TAKEAWAY:

• During more than 3 million person-years of follow-up, 2544 new cases of CRC were documented.
• The 10-year cumulative incidence of CRC was 1.98% among regular aspirin users compared with 2.95% among nonusers, corresponding to an ARR of 0.97%.
• The ARR associated with aspirin use was greatest among individuals with the unhealthiest lifestyle scores and progressively decreased with healthier lifestyle scores (P < .001 for additive interaction).
• Those with the unhealthiest lifestyle scores (0-1) had a 10-year ARR of 1.28% from aspirin use, whereas those with the healthiest lifestyle scores (4-5) had an ARR of 0.11%.
• The number needed to treat with aspirin for 10 years to prevent one CRC case was 78 for those with the unhealthiest lifestyles, compared with 909 for those with the healthiest lifestyles.
• Among the individual components of the healthy lifestyle score, higher BMI and smoking correlated with greater reductions in CRC risk from aspirin use.

IN PRACTICE:

“These results support the use of lifestyle risk factors to identify individuals who may have a more favorable risk-benefit profile for cancer prevention with aspirin,” the authors wrote. 

SOURCE:

The study, with first author Daniel R. Sikavi, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study population consisted of health professionals who were predominantly White, which may limit generalizability of the findings. Lifestyle factors and aspirin use were self-reported, which may introduce measurement errors. The study did not systematically assess adverse outcomes potentially due to aspirin use or the presence of a known hereditary cancer syndrome. 

DISCLOSURES:

The study had no commercial funding. The authors had no relevant conflicts of interest.

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