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Do Clonal Hematopoiesis and Mosaic Chromosomal Alterations Increase Solid Tumor Risk?
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.
FROM CANCER
Prediction, Management of Sjögren-Related Lymphomas Gain Ground With New Studies
, particularly mucosa-associated lymphoid tissue (MALT) lymphoma, based on recent findings that confirmed a key early biomarker and found that a systemic treatment strategy reduced Sjögren disease activity and the risk for lymphoma relapse.
Two European studies published in The Lancet Rheumatology — one a case-control study reporting that rheumatoid factor (RF) was an early and strong predictor of Sjögren disease–related MALT lymphoma and the other a retrospective study that found a combination of chemotherapy and anti-CD20 therapy with rituximab as a first-line treatment for lymphoma was more effective than localized treatment or watch-and-wait approach in minimizing autoimmune activity and treating the lymphoma — potentially shed new light on strategies to manage Sjögren disease–related lymphoma.
A commentary accompanying the studies noted that 5%-10% of patients with Sjögren disease will develop non-Hodgkin B-cell lymphoma, with marginal lymphoma the most common type of low-grade lymphoma. The commentary, led by Suzanne Arends, MD, a rheumatologist at the University of Groningen in Groningen, the Netherlands, found the studies “clinically relevant” but stated that the lack of consistent definitions between the two studies along with their retrospective nature prevent any “definitive conclusions.”
High Lymphoma Risk in Sjögren Disease
“It is the autoimmune disease in which the risk of lymphoma is the highest, a 10- to 20-fold increase of the risk of lymphoma in this disease,” Xavier Mariette, MD, PhD, co-senior author of the retrospective treatment study, said of Sjögren disease.
These lymphomas are predominantly the marginal zone type, specifically MALT occurring in the salivary glands, the same site of the autoimmune disease, said Dr. Mariette, who is the head of Rheumatology and professor at Université Paris-Saclay and Hôpital Bicêtre. Autoimmune B cells become lymphomatous. “So there is a continuity between autoimmunity and lymphoma genesis,” Dr. Mariette told this news organization. Typically, hematologists do not treat the lymphoma if it doesn’t migrate beyond the salivary glands, he said.
Dr. Mariette said his group’s findings make the case for a more aggressive treatment.
“When patients got the systemic treatment, there was a decreased risk of flare of the autoimmune disease of Sjögren’s, but there was no effect on the lymphoma formation,” Dr. Mariette said. “And when these patients have combined therapy, immunotherapy plus chemotherapy, compared to single immunotherapy, they did have improvement of the lymphoma progression-free survival.”
Their multicenter study enrolled 106 patients with Sjögren disease who developed lymphoma, 64% (n = 68) of whom had MALT, 13% (n = 14) of whom had other marginal zone subtypes, and the same percentage with diffuse large B-cell lymphoma. With a median follow-up of 7 years, 32 patients with marginal zone subtypes who had combination chemotherapy and anti-CD20 therapy had a 64% greater chance of lymphoma progression-free survival than 18 of their counterparts who received anti-CD20 monotherapy. Overall, outcomes for Sjögren disease systemic activity or survival were no different between the combination therapy and monotherapy arms.
Patients who had a systemic approach had a 57% reduced risk for new Sjögren disease activity compared with those who had first-line surgery or radiation (16%, n = 13) or underwent watch and wait (23%, n = 19).
The study strengthens the argument for a systemic treatment approach over localized therapy “because patients with Sjögren’s have a higher degree of development of MALT lymphoma of the salivary glands,” Juan Pablo Alderuccio, MD, a hematologist and lymphoma clinical site disease group leader at the Sylvester Comprehensive Cancer Center at the University of Miami Health Systems, Miami, Florida, told this news organization.
“We already knew that the combination of chemotherapy with rituximab usually achieves a better outcome,” Dr. Alderuccio added, citing a 2017 clinical trial that found combined chemotherapy with chlorambucil plus rituximab improved progression-free survival compared with either therapy alone. The latest retrospective study from France reinforces that, he said.
“The study also shows it’s very important to consider treatment-related specificities — to select the most appropriate treatment for these patients,” Dr. Alderuccio added.
RF Biomarker
The case-control study by researchers in Italy and Greece included 80 patients with Sjögren-related MALT lymphoma matched to controls with Sjögren disease who did not have lymphoma.
“We showed that rheumatoid factor positivity at the time of Sjögren’s disease diagnosis serves as the most reliable and temporally distant independent predictor of MALT lymphoma development,” lead author Andreas Goules, MD, a pathophysiologist at the National and Kapodistrian University of Athens, Athens, Greece, told this news organization.
He added that the study found that specific biomarkers in addition to RF positivity were signs of a high risk for MALT lymphoma and a more advanced stage of Sjögren disease–related lymphomagenesis. They included high systemic disease activity, measured as a European Alliance of Associations for Rheumatology Sjögren’s Syndrome Disease Activity Index ≥ 5, and specific B-cell manifestations, such as cryoglobulinemia, salivary gland enlargement, hypocomplementemia, and palpable purpura.
“Ideally, all patients should be evaluated at the time of diagnosis for the presence of RF and undergo a minor salivary gland biopsy to exclude an underlying ongoing lymphoproliferative process,” Dr. Goules said.
RF-positive patients with Sjögren disease require a closer follow-up to identify an advanced stage of lymphoma development, he added.
“It is well known that Sjögren’s disease is characterized by an increased mortality rate, compared to the general population, mainly due to the related lymphomas,” Dr. Goules added. “Thus, the early diagnosis of MALT lymphoma, which is associated with a better prognosis, is expected to improve the overall clinical outcome of Sjögren’s disease patients.”
Rheumatologists and hematologists should employ a similar strategy for Sjögren disease–related large B-cell lymphomas, he said.
“The pathogenetic mechanisms of these two lymphoma types are vastly different, so it wouldn’t be surprising if an entirely different risk factor emerges,” Dr. Goules said. “However, given the rarity of diffuse large B-cell lymphomas, much larger multinational cohorts will be necessary to obtain clinically and pathogenetically meaningful results.”
Alan Baer, MD, a rheumatologist and founder of the Sjögren’s Disease Clinic at Johns Hopkins University in Baltimore, noted Dr. Goules and colleagues are not the first to identify RF, along with a host of other clinical and laboratory findings, as a risk factor for lymphoma in patients with Sjögren disease. “The current study validates rheumatoid factor as an independent risk factor present at a time that is temporally distant from the time of lymphoma diagnosis,” he said.
However, he cautioned that RF alone isn’t highly predictive of Sjögren-related lymphoma. Up to 60% of patients with Sjögren disease are positive for RF at the time of the diagnosis, Dr. Baer said.
“Thus, the finding of rheumatoid factor alone does not necessarily mandate closer surveillance of this group of patients, with the potential for more frequent clinical exams, imaging, and laboratory testing,” he said. “Such an approach has the risk of subjecting patients to unnecessary testing, including invasive procedures.”
More detailed findings, such as if a certain RF level was more predictive of lymphoma or whether other features in combination with RF heightened the risk, would be helpful, he said.
What Future Studies Should Look At
The studies call for further research into biomarkers for Sjögren disease–related lymphoma and treatment of the disease, both Dr. Mariette and Dr. Goules said.
Dr. Goules said a multicenter prospective study is needed to measure RF positivity and RF titers over time and determine whether higher levels mean an increased risk for lymphoma development or a shorter time interval until lymphoma onset. “Such a study requires a large number of RF-positive Sjögren’s disease patients who would be followed up for a long period of time,” Dr. Goules said.
To further evaluate treatment approaches for Sjögren disease–related lymphoma, Dr. Mariette said, a prospective study should compare the watch-and-wait approach with combination chemotherapy and anti-CD20 therapy. “It would be difficult to run because the primary endpoint would be lymphoma progression–free survival, and the secondary would be Sjögren’s relapse and mortality, but it would take a lot of time,” he said.
He added, “It’s a reason why this retrospective study is important. Maybe if we had another retrospective study reaching the same conclusion, I think it would be very, very strong evidence.”
Funding for the case-control study came from the European Commission–Horizon 2020 program. The retrospective treatment study had no outside funding. Dr. Mariette disclosed financial relationships with AstraZeneca, Bristol-Myers Squibb, Galapagos, GlaxoSmithKline, Novartis, and Pfizer. Dr. Alderuccio, Dr. Goules, and Dr. Baer had no relevant relationships to disclose.
A version of this article first appeared on Medscape.com.
, particularly mucosa-associated lymphoid tissue (MALT) lymphoma, based on recent findings that confirmed a key early biomarker and found that a systemic treatment strategy reduced Sjögren disease activity and the risk for lymphoma relapse.
Two European studies published in The Lancet Rheumatology — one a case-control study reporting that rheumatoid factor (RF) was an early and strong predictor of Sjögren disease–related MALT lymphoma and the other a retrospective study that found a combination of chemotherapy and anti-CD20 therapy with rituximab as a first-line treatment for lymphoma was more effective than localized treatment or watch-and-wait approach in minimizing autoimmune activity and treating the lymphoma — potentially shed new light on strategies to manage Sjögren disease–related lymphoma.
A commentary accompanying the studies noted that 5%-10% of patients with Sjögren disease will develop non-Hodgkin B-cell lymphoma, with marginal lymphoma the most common type of low-grade lymphoma. The commentary, led by Suzanne Arends, MD, a rheumatologist at the University of Groningen in Groningen, the Netherlands, found the studies “clinically relevant” but stated that the lack of consistent definitions between the two studies along with their retrospective nature prevent any “definitive conclusions.”
High Lymphoma Risk in Sjögren Disease
“It is the autoimmune disease in which the risk of lymphoma is the highest, a 10- to 20-fold increase of the risk of lymphoma in this disease,” Xavier Mariette, MD, PhD, co-senior author of the retrospective treatment study, said of Sjögren disease.
These lymphomas are predominantly the marginal zone type, specifically MALT occurring in the salivary glands, the same site of the autoimmune disease, said Dr. Mariette, who is the head of Rheumatology and professor at Université Paris-Saclay and Hôpital Bicêtre. Autoimmune B cells become lymphomatous. “So there is a continuity between autoimmunity and lymphoma genesis,” Dr. Mariette told this news organization. Typically, hematologists do not treat the lymphoma if it doesn’t migrate beyond the salivary glands, he said.
Dr. Mariette said his group’s findings make the case for a more aggressive treatment.
“When patients got the systemic treatment, there was a decreased risk of flare of the autoimmune disease of Sjögren’s, but there was no effect on the lymphoma formation,” Dr. Mariette said. “And when these patients have combined therapy, immunotherapy plus chemotherapy, compared to single immunotherapy, they did have improvement of the lymphoma progression-free survival.”
Their multicenter study enrolled 106 patients with Sjögren disease who developed lymphoma, 64% (n = 68) of whom had MALT, 13% (n = 14) of whom had other marginal zone subtypes, and the same percentage with diffuse large B-cell lymphoma. With a median follow-up of 7 years, 32 patients with marginal zone subtypes who had combination chemotherapy and anti-CD20 therapy had a 64% greater chance of lymphoma progression-free survival than 18 of their counterparts who received anti-CD20 monotherapy. Overall, outcomes for Sjögren disease systemic activity or survival were no different between the combination therapy and monotherapy arms.
Patients who had a systemic approach had a 57% reduced risk for new Sjögren disease activity compared with those who had first-line surgery or radiation (16%, n = 13) or underwent watch and wait (23%, n = 19).
The study strengthens the argument for a systemic treatment approach over localized therapy “because patients with Sjögren’s have a higher degree of development of MALT lymphoma of the salivary glands,” Juan Pablo Alderuccio, MD, a hematologist and lymphoma clinical site disease group leader at the Sylvester Comprehensive Cancer Center at the University of Miami Health Systems, Miami, Florida, told this news organization.
“We already knew that the combination of chemotherapy with rituximab usually achieves a better outcome,” Dr. Alderuccio added, citing a 2017 clinical trial that found combined chemotherapy with chlorambucil plus rituximab improved progression-free survival compared with either therapy alone. The latest retrospective study from France reinforces that, he said.
“The study also shows it’s very important to consider treatment-related specificities — to select the most appropriate treatment for these patients,” Dr. Alderuccio added.
RF Biomarker
The case-control study by researchers in Italy and Greece included 80 patients with Sjögren-related MALT lymphoma matched to controls with Sjögren disease who did not have lymphoma.
“We showed that rheumatoid factor positivity at the time of Sjögren’s disease diagnosis serves as the most reliable and temporally distant independent predictor of MALT lymphoma development,” lead author Andreas Goules, MD, a pathophysiologist at the National and Kapodistrian University of Athens, Athens, Greece, told this news organization.
He added that the study found that specific biomarkers in addition to RF positivity were signs of a high risk for MALT lymphoma and a more advanced stage of Sjögren disease–related lymphomagenesis. They included high systemic disease activity, measured as a European Alliance of Associations for Rheumatology Sjögren’s Syndrome Disease Activity Index ≥ 5, and specific B-cell manifestations, such as cryoglobulinemia, salivary gland enlargement, hypocomplementemia, and palpable purpura.
“Ideally, all patients should be evaluated at the time of diagnosis for the presence of RF and undergo a minor salivary gland biopsy to exclude an underlying ongoing lymphoproliferative process,” Dr. Goules said.
RF-positive patients with Sjögren disease require a closer follow-up to identify an advanced stage of lymphoma development, he added.
“It is well known that Sjögren’s disease is characterized by an increased mortality rate, compared to the general population, mainly due to the related lymphomas,” Dr. Goules added. “Thus, the early diagnosis of MALT lymphoma, which is associated with a better prognosis, is expected to improve the overall clinical outcome of Sjögren’s disease patients.”
Rheumatologists and hematologists should employ a similar strategy for Sjögren disease–related large B-cell lymphomas, he said.
“The pathogenetic mechanisms of these two lymphoma types are vastly different, so it wouldn’t be surprising if an entirely different risk factor emerges,” Dr. Goules said. “However, given the rarity of diffuse large B-cell lymphomas, much larger multinational cohorts will be necessary to obtain clinically and pathogenetically meaningful results.”
Alan Baer, MD, a rheumatologist and founder of the Sjögren’s Disease Clinic at Johns Hopkins University in Baltimore, noted Dr. Goules and colleagues are not the first to identify RF, along with a host of other clinical and laboratory findings, as a risk factor for lymphoma in patients with Sjögren disease. “The current study validates rheumatoid factor as an independent risk factor present at a time that is temporally distant from the time of lymphoma diagnosis,” he said.
However, he cautioned that RF alone isn’t highly predictive of Sjögren-related lymphoma. Up to 60% of patients with Sjögren disease are positive for RF at the time of the diagnosis, Dr. Baer said.
“Thus, the finding of rheumatoid factor alone does not necessarily mandate closer surveillance of this group of patients, with the potential for more frequent clinical exams, imaging, and laboratory testing,” he said. “Such an approach has the risk of subjecting patients to unnecessary testing, including invasive procedures.”
More detailed findings, such as if a certain RF level was more predictive of lymphoma or whether other features in combination with RF heightened the risk, would be helpful, he said.
What Future Studies Should Look At
The studies call for further research into biomarkers for Sjögren disease–related lymphoma and treatment of the disease, both Dr. Mariette and Dr. Goules said.
Dr. Goules said a multicenter prospective study is needed to measure RF positivity and RF titers over time and determine whether higher levels mean an increased risk for lymphoma development or a shorter time interval until lymphoma onset. “Such a study requires a large number of RF-positive Sjögren’s disease patients who would be followed up for a long period of time,” Dr. Goules said.
To further evaluate treatment approaches for Sjögren disease–related lymphoma, Dr. Mariette said, a prospective study should compare the watch-and-wait approach with combination chemotherapy and anti-CD20 therapy. “It would be difficult to run because the primary endpoint would be lymphoma progression–free survival, and the secondary would be Sjögren’s relapse and mortality, but it would take a lot of time,” he said.
He added, “It’s a reason why this retrospective study is important. Maybe if we had another retrospective study reaching the same conclusion, I think it would be very, very strong evidence.”
Funding for the case-control study came from the European Commission–Horizon 2020 program. The retrospective treatment study had no outside funding. Dr. Mariette disclosed financial relationships with AstraZeneca, Bristol-Myers Squibb, Galapagos, GlaxoSmithKline, Novartis, and Pfizer. Dr. Alderuccio, Dr. Goules, and Dr. Baer had no relevant relationships to disclose.
A version of this article first appeared on Medscape.com.
, particularly mucosa-associated lymphoid tissue (MALT) lymphoma, based on recent findings that confirmed a key early biomarker and found that a systemic treatment strategy reduced Sjögren disease activity and the risk for lymphoma relapse.
Two European studies published in The Lancet Rheumatology — one a case-control study reporting that rheumatoid factor (RF) was an early and strong predictor of Sjögren disease–related MALT lymphoma and the other a retrospective study that found a combination of chemotherapy and anti-CD20 therapy with rituximab as a first-line treatment for lymphoma was more effective than localized treatment or watch-and-wait approach in minimizing autoimmune activity and treating the lymphoma — potentially shed new light on strategies to manage Sjögren disease–related lymphoma.
A commentary accompanying the studies noted that 5%-10% of patients with Sjögren disease will develop non-Hodgkin B-cell lymphoma, with marginal lymphoma the most common type of low-grade lymphoma. The commentary, led by Suzanne Arends, MD, a rheumatologist at the University of Groningen in Groningen, the Netherlands, found the studies “clinically relevant” but stated that the lack of consistent definitions between the two studies along with their retrospective nature prevent any “definitive conclusions.”
High Lymphoma Risk in Sjögren Disease
“It is the autoimmune disease in which the risk of lymphoma is the highest, a 10- to 20-fold increase of the risk of lymphoma in this disease,” Xavier Mariette, MD, PhD, co-senior author of the retrospective treatment study, said of Sjögren disease.
These lymphomas are predominantly the marginal zone type, specifically MALT occurring in the salivary glands, the same site of the autoimmune disease, said Dr. Mariette, who is the head of Rheumatology and professor at Université Paris-Saclay and Hôpital Bicêtre. Autoimmune B cells become lymphomatous. “So there is a continuity between autoimmunity and lymphoma genesis,” Dr. Mariette told this news organization. Typically, hematologists do not treat the lymphoma if it doesn’t migrate beyond the salivary glands, he said.
Dr. Mariette said his group’s findings make the case for a more aggressive treatment.
“When patients got the systemic treatment, there was a decreased risk of flare of the autoimmune disease of Sjögren’s, but there was no effect on the lymphoma formation,” Dr. Mariette said. “And when these patients have combined therapy, immunotherapy plus chemotherapy, compared to single immunotherapy, they did have improvement of the lymphoma progression-free survival.”
Their multicenter study enrolled 106 patients with Sjögren disease who developed lymphoma, 64% (n = 68) of whom had MALT, 13% (n = 14) of whom had other marginal zone subtypes, and the same percentage with diffuse large B-cell lymphoma. With a median follow-up of 7 years, 32 patients with marginal zone subtypes who had combination chemotherapy and anti-CD20 therapy had a 64% greater chance of lymphoma progression-free survival than 18 of their counterparts who received anti-CD20 monotherapy. Overall, outcomes for Sjögren disease systemic activity or survival were no different between the combination therapy and monotherapy arms.
Patients who had a systemic approach had a 57% reduced risk for new Sjögren disease activity compared with those who had first-line surgery or radiation (16%, n = 13) or underwent watch and wait (23%, n = 19).
The study strengthens the argument for a systemic treatment approach over localized therapy “because patients with Sjögren’s have a higher degree of development of MALT lymphoma of the salivary glands,” Juan Pablo Alderuccio, MD, a hematologist and lymphoma clinical site disease group leader at the Sylvester Comprehensive Cancer Center at the University of Miami Health Systems, Miami, Florida, told this news organization.
“We already knew that the combination of chemotherapy with rituximab usually achieves a better outcome,” Dr. Alderuccio added, citing a 2017 clinical trial that found combined chemotherapy with chlorambucil plus rituximab improved progression-free survival compared with either therapy alone. The latest retrospective study from France reinforces that, he said.
“The study also shows it’s very important to consider treatment-related specificities — to select the most appropriate treatment for these patients,” Dr. Alderuccio added.
RF Biomarker
The case-control study by researchers in Italy and Greece included 80 patients with Sjögren-related MALT lymphoma matched to controls with Sjögren disease who did not have lymphoma.
“We showed that rheumatoid factor positivity at the time of Sjögren’s disease diagnosis serves as the most reliable and temporally distant independent predictor of MALT lymphoma development,” lead author Andreas Goules, MD, a pathophysiologist at the National and Kapodistrian University of Athens, Athens, Greece, told this news organization.
He added that the study found that specific biomarkers in addition to RF positivity were signs of a high risk for MALT lymphoma and a more advanced stage of Sjögren disease–related lymphomagenesis. They included high systemic disease activity, measured as a European Alliance of Associations for Rheumatology Sjögren’s Syndrome Disease Activity Index ≥ 5, and specific B-cell manifestations, such as cryoglobulinemia, salivary gland enlargement, hypocomplementemia, and palpable purpura.
“Ideally, all patients should be evaluated at the time of diagnosis for the presence of RF and undergo a minor salivary gland biopsy to exclude an underlying ongoing lymphoproliferative process,” Dr. Goules said.
RF-positive patients with Sjögren disease require a closer follow-up to identify an advanced stage of lymphoma development, he added.
“It is well known that Sjögren’s disease is characterized by an increased mortality rate, compared to the general population, mainly due to the related lymphomas,” Dr. Goules added. “Thus, the early diagnosis of MALT lymphoma, which is associated with a better prognosis, is expected to improve the overall clinical outcome of Sjögren’s disease patients.”
Rheumatologists and hematologists should employ a similar strategy for Sjögren disease–related large B-cell lymphomas, he said.
“The pathogenetic mechanisms of these two lymphoma types are vastly different, so it wouldn’t be surprising if an entirely different risk factor emerges,” Dr. Goules said. “However, given the rarity of diffuse large B-cell lymphomas, much larger multinational cohorts will be necessary to obtain clinically and pathogenetically meaningful results.”
Alan Baer, MD, a rheumatologist and founder of the Sjögren’s Disease Clinic at Johns Hopkins University in Baltimore, noted Dr. Goules and colleagues are not the first to identify RF, along with a host of other clinical and laboratory findings, as a risk factor for lymphoma in patients with Sjögren disease. “The current study validates rheumatoid factor as an independent risk factor present at a time that is temporally distant from the time of lymphoma diagnosis,” he said.
However, he cautioned that RF alone isn’t highly predictive of Sjögren-related lymphoma. Up to 60% of patients with Sjögren disease are positive for RF at the time of the diagnosis, Dr. Baer said.
“Thus, the finding of rheumatoid factor alone does not necessarily mandate closer surveillance of this group of patients, with the potential for more frequent clinical exams, imaging, and laboratory testing,” he said. “Such an approach has the risk of subjecting patients to unnecessary testing, including invasive procedures.”
More detailed findings, such as if a certain RF level was more predictive of lymphoma or whether other features in combination with RF heightened the risk, would be helpful, he said.
What Future Studies Should Look At
The studies call for further research into biomarkers for Sjögren disease–related lymphoma and treatment of the disease, both Dr. Mariette and Dr. Goules said.
Dr. Goules said a multicenter prospective study is needed to measure RF positivity and RF titers over time and determine whether higher levels mean an increased risk for lymphoma development or a shorter time interval until lymphoma onset. “Such a study requires a large number of RF-positive Sjögren’s disease patients who would be followed up for a long period of time,” Dr. Goules said.
To further evaluate treatment approaches for Sjögren disease–related lymphoma, Dr. Mariette said, a prospective study should compare the watch-and-wait approach with combination chemotherapy and anti-CD20 therapy. “It would be difficult to run because the primary endpoint would be lymphoma progression–free survival, and the secondary would be Sjögren’s relapse and mortality, but it would take a lot of time,” he said.
He added, “It’s a reason why this retrospective study is important. Maybe if we had another retrospective study reaching the same conclusion, I think it would be very, very strong evidence.”
Funding for the case-control study came from the European Commission–Horizon 2020 program. The retrospective treatment study had no outside funding. Dr. Mariette disclosed financial relationships with AstraZeneca, Bristol-Myers Squibb, Galapagos, GlaxoSmithKline, Novartis, and Pfizer. Dr. Alderuccio, Dr. Goules, and Dr. Baer had no relevant relationships to disclose.
A version of this article first appeared on Medscape.com.
FROM THE LANCET RHEUMATOLOGY
Teclistamab Promising as a Treatment of Last Resort for Refractory Autoimmune Diseases
TOPLINE:
Teclistamab, a T-cell engager that targets B-cell maturation antigen (BCMA), improved disease activity in four patients with refractory autoimmune conditions. In a separately published case report, teclistamab treatment induced remission in a patient with refractory systemic lupus erythematosus (SLE).
BACKGROUND:
- Chimeric antigen receptor (CAR) T cells or T-cell engagers against CD19 have been effective in small studies of patients with treatment-resistant autoimmune diseases.
- Some patients have disease rooted in long-lived plasma cells that express BCMA but not CD19, making them resistant to CD19 CAR T-cell therapy.
- Teclistamab acts on T cells through CD3 and targets plasmablasts and plasma cells through BCMA.
METHODOLOGY:
- In one case series, researchers administered teclistamab subcutaneously to four patients with autoimmune diseases resistant to more than five immunosuppressants, including rituximab.
- Patient 1 had systemic sclerosis, patient 2 had primary Sjögren disease, patient 3 had idiopathic inflammatory myositis, and patient 4 had rheumatoid arthritis.
- Researchers incrementally increased teclistamab dosage in an inpatient setting: 0.06 mg/kg on day 1, 0.3 mg/kg on day 3, and 1.5 mg/kg on day 5. Patients 2, 3, and 4 received one maintenance dose of 1.5 mg/kg after 4 weeks, and patient 1 received a 1.5-mg/kg dose after 12 weeks.
- In the single case report, the patient with SLE received a step-up dosage of teclistamab (0.06 mg/kg and 0.3 mg/kg) followed by 0.8 mg/kg on day 7. She received 1.5 mg/kg at weeks 2 and 5.
TAKEAWAY:
- Teclistamab therapy led to significant improvements in disease activity in all four patients, with notable reductions in skin disease, arthritis, and lung function scores.
- Teclistamab therapy had a good safety profile, with no neurotoxicity or myelotoxicity and only lower-grade cytokine release syndrome reported.
- Researchers observed seroconversion of PM-Scl-75, PM-Scl-100, rheumatoid factor, and autoantibodies against mutated citrullinated vimentin and lower levels of autoantibodies ANA, MDAS, SS-A/Ro, SS-B/La, and PL-7 after treatment.
- In the separate case report, the patient reached complete drug-free remission by week 6, as defined by the Systemic Lupus Erythematosus Disease Activity Index 2000.
- The level of anti–double-stranded DNA antibodies in the patient with SLE decreased rapidly, reaching normal range by week 5 and remaining undetectable through week 16.
IN PRACTICE:
“These data show that the targeting of the plasma-cell compartment by a BCMA-targeted T-cell engager is feasible in patients with autoimmune disease. Whether such therapy results in sustained clinical remission warrants further study,” write the authors of the four-patient case series.
SOURCE:
Melanie Hagen, MD, Friedrich Alexander University Erlangen–Nuremberg, Germany, and colleagues reported their case series online in The New England Journal of Medicine. Tobias Alexander, MD, and colleagues at Charité–Universitätsmedizin Berlin, Germany, also described their single case report in The New England Journal of Medicine.
LIMITATIONS:
The small number of patients limits the generalizability of the findings. The short duration of follow-up may not capture long-term effects and potential late-onset adverse events. The lack of a control group makes it difficult to attribute improvements solely to teclistamab therapy.
DISCLOSURES:
The four-patient case series was supported by grants from the Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, and the European Union. The single case report was supported by grants from the Deutsche Forschungsgemeinschaft and the European Union. Several authors have disclosed financial relationships with pharmaceutical companies, including Janssen Biotech, which markets teclistamab.
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:
Teclistamab, a T-cell engager that targets B-cell maturation antigen (BCMA), improved disease activity in four patients with refractory autoimmune conditions. In a separately published case report, teclistamab treatment induced remission in a patient with refractory systemic lupus erythematosus (SLE).
BACKGROUND:
- Chimeric antigen receptor (CAR) T cells or T-cell engagers against CD19 have been effective in small studies of patients with treatment-resistant autoimmune diseases.
- Some patients have disease rooted in long-lived plasma cells that express BCMA but not CD19, making them resistant to CD19 CAR T-cell therapy.
- Teclistamab acts on T cells through CD3 and targets plasmablasts and plasma cells through BCMA.
METHODOLOGY:
- In one case series, researchers administered teclistamab subcutaneously to four patients with autoimmune diseases resistant to more than five immunosuppressants, including rituximab.
- Patient 1 had systemic sclerosis, patient 2 had primary Sjögren disease, patient 3 had idiopathic inflammatory myositis, and patient 4 had rheumatoid arthritis.
- Researchers incrementally increased teclistamab dosage in an inpatient setting: 0.06 mg/kg on day 1, 0.3 mg/kg on day 3, and 1.5 mg/kg on day 5. Patients 2, 3, and 4 received one maintenance dose of 1.5 mg/kg after 4 weeks, and patient 1 received a 1.5-mg/kg dose after 12 weeks.
- In the single case report, the patient with SLE received a step-up dosage of teclistamab (0.06 mg/kg and 0.3 mg/kg) followed by 0.8 mg/kg on day 7. She received 1.5 mg/kg at weeks 2 and 5.
TAKEAWAY:
- Teclistamab therapy led to significant improvements in disease activity in all four patients, with notable reductions in skin disease, arthritis, and lung function scores.
- Teclistamab therapy had a good safety profile, with no neurotoxicity or myelotoxicity and only lower-grade cytokine release syndrome reported.
- Researchers observed seroconversion of PM-Scl-75, PM-Scl-100, rheumatoid factor, and autoantibodies against mutated citrullinated vimentin and lower levels of autoantibodies ANA, MDAS, SS-A/Ro, SS-B/La, and PL-7 after treatment.
- In the separate case report, the patient reached complete drug-free remission by week 6, as defined by the Systemic Lupus Erythematosus Disease Activity Index 2000.
- The level of anti–double-stranded DNA antibodies in the patient with SLE decreased rapidly, reaching normal range by week 5 and remaining undetectable through week 16.
IN PRACTICE:
“These data show that the targeting of the plasma-cell compartment by a BCMA-targeted T-cell engager is feasible in patients with autoimmune disease. Whether such therapy results in sustained clinical remission warrants further study,” write the authors of the four-patient case series.
SOURCE:
Melanie Hagen, MD, Friedrich Alexander University Erlangen–Nuremberg, Germany, and colleagues reported their case series online in The New England Journal of Medicine. Tobias Alexander, MD, and colleagues at Charité–Universitätsmedizin Berlin, Germany, also described their single case report in The New England Journal of Medicine.
LIMITATIONS:
The small number of patients limits the generalizability of the findings. The short duration of follow-up may not capture long-term effects and potential late-onset adverse events. The lack of a control group makes it difficult to attribute improvements solely to teclistamab therapy.
DISCLOSURES:
The four-patient case series was supported by grants from the Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, and the European Union. The single case report was supported by grants from the Deutsche Forschungsgemeinschaft and the European Union. Several authors have disclosed financial relationships with pharmaceutical companies, including Janssen Biotech, which markets teclistamab.
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:
Teclistamab, a T-cell engager that targets B-cell maturation antigen (BCMA), improved disease activity in four patients with refractory autoimmune conditions. In a separately published case report, teclistamab treatment induced remission in a patient with refractory systemic lupus erythematosus (SLE).
BACKGROUND:
- Chimeric antigen receptor (CAR) T cells or T-cell engagers against CD19 have been effective in small studies of patients with treatment-resistant autoimmune diseases.
- Some patients have disease rooted in long-lived plasma cells that express BCMA but not CD19, making them resistant to CD19 CAR T-cell therapy.
- Teclistamab acts on T cells through CD3 and targets plasmablasts and plasma cells through BCMA.
METHODOLOGY:
- In one case series, researchers administered teclistamab subcutaneously to four patients with autoimmune diseases resistant to more than five immunosuppressants, including rituximab.
- Patient 1 had systemic sclerosis, patient 2 had primary Sjögren disease, patient 3 had idiopathic inflammatory myositis, and patient 4 had rheumatoid arthritis.
- Researchers incrementally increased teclistamab dosage in an inpatient setting: 0.06 mg/kg on day 1, 0.3 mg/kg on day 3, and 1.5 mg/kg on day 5. Patients 2, 3, and 4 received one maintenance dose of 1.5 mg/kg after 4 weeks, and patient 1 received a 1.5-mg/kg dose after 12 weeks.
- In the single case report, the patient with SLE received a step-up dosage of teclistamab (0.06 mg/kg and 0.3 mg/kg) followed by 0.8 mg/kg on day 7. She received 1.5 mg/kg at weeks 2 and 5.
TAKEAWAY:
- Teclistamab therapy led to significant improvements in disease activity in all four patients, with notable reductions in skin disease, arthritis, and lung function scores.
- Teclistamab therapy had a good safety profile, with no neurotoxicity or myelotoxicity and only lower-grade cytokine release syndrome reported.
- Researchers observed seroconversion of PM-Scl-75, PM-Scl-100, rheumatoid factor, and autoantibodies against mutated citrullinated vimentin and lower levels of autoantibodies ANA, MDAS, SS-A/Ro, SS-B/La, and PL-7 after treatment.
- In the separate case report, the patient reached complete drug-free remission by week 6, as defined by the Systemic Lupus Erythematosus Disease Activity Index 2000.
- The level of anti–double-stranded DNA antibodies in the patient with SLE decreased rapidly, reaching normal range by week 5 and remaining undetectable through week 16.
IN PRACTICE:
“These data show that the targeting of the plasma-cell compartment by a BCMA-targeted T-cell engager is feasible in patients with autoimmune disease. Whether such therapy results in sustained clinical remission warrants further study,” write the authors of the four-patient case series.
SOURCE:
Melanie Hagen, MD, Friedrich Alexander University Erlangen–Nuremberg, Germany, and colleagues reported their case series online in The New England Journal of Medicine. Tobias Alexander, MD, and colleagues at Charité–Universitätsmedizin Berlin, Germany, also described their single case report in The New England Journal of Medicine.
LIMITATIONS:
The small number of patients limits the generalizability of the findings. The short duration of follow-up may not capture long-term effects and potential late-onset adverse events. The lack of a control group makes it difficult to attribute improvements solely to teclistamab therapy.
DISCLOSURES:
The four-patient case series was supported by grants from the Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, and the European Union. The single case report was supported by grants from the Deutsche Forschungsgemeinschaft and the European Union. Several authors have disclosed financial relationships with pharmaceutical companies, including Janssen Biotech, which markets teclistamab.
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.
Seated Doctors Better Satisfy Patients, Communication
During a busy day of consultations, however, it can be difficult for healthcare professionals to sit regularly with patients. Previous studies have revealed that hospital doctors sit during one out of every five meetings with patients.
A recent US study evaluated the impact of the practitioner’s seated position next to the patient on the quality of the doctor-patient interaction in an internal medicine department. This research involved a sample of 51 doctors (average age, 35 years; 51% men) and analyzed 125 clinical interviews (n = 125 patients; average age, 53 years; 55% men). Participants were not informed of the real objective of the study. The patient’s perception of medical care was also solicited.
The experimental protocol involved two distinct configurations. Either the chair was positioned near the bed (within 90 cm) before the doctor arrived or it remained visible in its usual place. Each meeting with a patient was randomized according to the chair location (intervention group: n = 60; control group: n = 65).
The primary criterion was the doctor’s binary decision to sit or not at a given moment during a meeting with a patient. Secondary criteria included patient satisfaction, time spent in the room, and the perception of time spent in the room by doctors and patients.
The chair’s location had no effect on the average duration of the interview, whether actual or estimated. When a chair was placed near the bed, the doctor sat in more than six out of 10 cases (63%), compared with fewer than one case out of 10 (8%) when the chair was less easily accessible (odds ratio, 20.7; 95% CI, 7.2-59.4; P < .001).
The chair arrangement did not lead to a significant difference in the average duration of presence in the room (10.6 min for both groups). Likewise, no notable difference was observed regarding the subjective estimation of this duration from the practitioners’ point of view (9.4 min vs 9.8 min) or from the patients’ point of view (13.1 min vs 13.5 min).
In the group in which the doctor sat to converse, patient satisfaction was significantly higher, with an overall difference of 3.9% (P = .02). Patients felt that the information provided was better (72% vs 52%; P =.03), and their confidence in the proposed care was also higher (58% vs 35%; P = .01). On the other hand, no significant difference appeared between the two groups regarding the information retained by the patient (doctor’s name and reason for hospitalization) or the doctor’s behavior.
The study authors acknowledged the study’s methodological limitations, which included a sample size that was lower than initially projected and the restriction to a single hospital setting. In addition, they noted that all patients were housed in individual rooms, which could be a source of bias. Despite these reservations, they suggested that even minimal environmental changes, such as the thoughtful placement of a chair, can significantly affect patients’ perceptions of the quality of care provided.
This story was translated from JIM, which is part of the Medscape professional network, 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.
During a busy day of consultations, however, it can be difficult for healthcare professionals to sit regularly with patients. Previous studies have revealed that hospital doctors sit during one out of every five meetings with patients.
A recent US study evaluated the impact of the practitioner’s seated position next to the patient on the quality of the doctor-patient interaction in an internal medicine department. This research involved a sample of 51 doctors (average age, 35 years; 51% men) and analyzed 125 clinical interviews (n = 125 patients; average age, 53 years; 55% men). Participants were not informed of the real objective of the study. The patient’s perception of medical care was also solicited.
The experimental protocol involved two distinct configurations. Either the chair was positioned near the bed (within 90 cm) before the doctor arrived or it remained visible in its usual place. Each meeting with a patient was randomized according to the chair location (intervention group: n = 60; control group: n = 65).
The primary criterion was the doctor’s binary decision to sit or not at a given moment during a meeting with a patient. Secondary criteria included patient satisfaction, time spent in the room, and the perception of time spent in the room by doctors and patients.
The chair’s location had no effect on the average duration of the interview, whether actual or estimated. When a chair was placed near the bed, the doctor sat in more than six out of 10 cases (63%), compared with fewer than one case out of 10 (8%) when the chair was less easily accessible (odds ratio, 20.7; 95% CI, 7.2-59.4; P < .001).
The chair arrangement did not lead to a significant difference in the average duration of presence in the room (10.6 min for both groups). Likewise, no notable difference was observed regarding the subjective estimation of this duration from the practitioners’ point of view (9.4 min vs 9.8 min) or from the patients’ point of view (13.1 min vs 13.5 min).
In the group in which the doctor sat to converse, patient satisfaction was significantly higher, with an overall difference of 3.9% (P = .02). Patients felt that the information provided was better (72% vs 52%; P =.03), and their confidence in the proposed care was also higher (58% vs 35%; P = .01). On the other hand, no significant difference appeared between the two groups regarding the information retained by the patient (doctor’s name and reason for hospitalization) or the doctor’s behavior.
The study authors acknowledged the study’s methodological limitations, which included a sample size that was lower than initially projected and the restriction to a single hospital setting. In addition, they noted that all patients were housed in individual rooms, which could be a source of bias. Despite these reservations, they suggested that even minimal environmental changes, such as the thoughtful placement of a chair, can significantly affect patients’ perceptions of the quality of care provided.
This story was translated from JIM, which is part of the Medscape professional network, 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.
During a busy day of consultations, however, it can be difficult for healthcare professionals to sit regularly with patients. Previous studies have revealed that hospital doctors sit during one out of every five meetings with patients.
A recent US study evaluated the impact of the practitioner’s seated position next to the patient on the quality of the doctor-patient interaction in an internal medicine department. This research involved a sample of 51 doctors (average age, 35 years; 51% men) and analyzed 125 clinical interviews (n = 125 patients; average age, 53 years; 55% men). Participants were not informed of the real objective of the study. The patient’s perception of medical care was also solicited.
The experimental protocol involved two distinct configurations. Either the chair was positioned near the bed (within 90 cm) before the doctor arrived or it remained visible in its usual place. Each meeting with a patient was randomized according to the chair location (intervention group: n = 60; control group: n = 65).
The primary criterion was the doctor’s binary decision to sit or not at a given moment during a meeting with a patient. Secondary criteria included patient satisfaction, time spent in the room, and the perception of time spent in the room by doctors and patients.
The chair’s location had no effect on the average duration of the interview, whether actual or estimated. When a chair was placed near the bed, the doctor sat in more than six out of 10 cases (63%), compared with fewer than one case out of 10 (8%) when the chair was less easily accessible (odds ratio, 20.7; 95% CI, 7.2-59.4; P < .001).
The chair arrangement did not lead to a significant difference in the average duration of presence in the room (10.6 min for both groups). Likewise, no notable difference was observed regarding the subjective estimation of this duration from the practitioners’ point of view (9.4 min vs 9.8 min) or from the patients’ point of view (13.1 min vs 13.5 min).
In the group in which the doctor sat to converse, patient satisfaction was significantly higher, with an overall difference of 3.9% (P = .02). Patients felt that the information provided was better (72% vs 52%; P =.03), and their confidence in the proposed care was also higher (58% vs 35%; P = .01). On the other hand, no significant difference appeared between the two groups regarding the information retained by the patient (doctor’s name and reason for hospitalization) or the doctor’s behavior.
The study authors acknowledged the study’s methodological limitations, which included a sample size that was lower than initially projected and the restriction to a single hospital setting. In addition, they noted that all patients were housed in individual rooms, which could be a source of bias. Despite these reservations, they suggested that even minimal environmental changes, such as the thoughtful placement of a chair, can significantly affect patients’ perceptions of the quality of care provided.
This story was translated from JIM, which is part of the Medscape professional network, 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.
Cancer Cases, Deaths in Men Predicted to Surge by 2050
TOPLINE:
— with substantial disparities in cancer cases and deaths by age and region of the world, a recent analysis found.
METHODOLOGY:
- Overall, men have higher cancer incidence and mortality rates, which can be largely attributed to a higher prevalence of modifiable risk factors such as smoking, alcohol consumption, and occupational carcinogens, as well as the underuse of cancer prevention, screening, and treatment services.
- To assess the burden of cancer in men of different ages and from different regions of the world, researchers analyzed data from the 2022 Global Cancer Observatory (GLOBOCAN), which provides national-level estimates for cancer cases and deaths.
- Study outcomes included the incidence, mortality, and prevalence of cancer among men in 2022, along with projections for 2050. Estimates were stratified by several factors, including age; region; and Human Development Index (HDI), a composite score for health, education, and standard of living.
- Researchers also calculated mortality-to-incidence ratios (MIRs) for various cancer types, where higher values indicate worse survival.
TAKEAWAY:
- The researchers reported an estimated 10.3 million cancer cases and 5.4 million deaths globally in 2022, with almost two thirds of cases and deaths occurring in men aged 65 years or older.
- By 2050, cancer cases and deaths were projected to increase by 84.3% (to 19 million) and 93.2% (to 10.5 million), respectively. The increase from 2022 to 2050 was more than twofold higher for older men and countries with low and medium HDI.
- In 2022, the estimated global cancer MIR among men was nearly 55%, with variations by cancer types, age, and HDI. The MIR was lowest for thyroid cancer (7.6%) and highest for pancreatic cancer (90.9%); among World Health Organization regions, Africa had the highest MIR (72.6%), while the Americas had the lowest MIR (39.1%); countries with the lowest HDI had the highest MIR (73.5% vs 41.1% for very high HDI).
- Lung cancer was the leading cause for cases and deaths in 2022 and was projected to remain the leading cause in 2050.
IN PRACTICE:
“Disparities in cancer incidence and mortality among men were observed across age groups, countries/territories, and HDI in 2022, with these disparities projected to widen further by 2050,” according to the authors, who called for efforts to “reduce disparities in cancer burden and ensure equity in cancer prevention and care for men across the globe.”
SOURCE:
The study, led by Habtamu Mellie Bizuayehu, PhD, School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, Australia, was published online in Cancer.
LIMITATIONS:
The findings may be influenced by the quality of GLOBOCAN data. Interpretation should be cautious as MIR may not fully reflect cancer outcome inequalities. The study did not include other measures of cancer burden, such as years of life lost or years lived with disability, which were unavailable from the data source.
DISCLOSURES:
The authors did not disclose any funding information. The authors declared no 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 first appeared on Medscape.com.
TOPLINE:
— with substantial disparities in cancer cases and deaths by age and region of the world, a recent analysis found.
METHODOLOGY:
- Overall, men have higher cancer incidence and mortality rates, which can be largely attributed to a higher prevalence of modifiable risk factors such as smoking, alcohol consumption, and occupational carcinogens, as well as the underuse of cancer prevention, screening, and treatment services.
- To assess the burden of cancer in men of different ages and from different regions of the world, researchers analyzed data from the 2022 Global Cancer Observatory (GLOBOCAN), which provides national-level estimates for cancer cases and deaths.
- Study outcomes included the incidence, mortality, and prevalence of cancer among men in 2022, along with projections for 2050. Estimates were stratified by several factors, including age; region; and Human Development Index (HDI), a composite score for health, education, and standard of living.
- Researchers also calculated mortality-to-incidence ratios (MIRs) for various cancer types, where higher values indicate worse survival.
TAKEAWAY:
- The researchers reported an estimated 10.3 million cancer cases and 5.4 million deaths globally in 2022, with almost two thirds of cases and deaths occurring in men aged 65 years or older.
- By 2050, cancer cases and deaths were projected to increase by 84.3% (to 19 million) and 93.2% (to 10.5 million), respectively. The increase from 2022 to 2050 was more than twofold higher for older men and countries with low and medium HDI.
- In 2022, the estimated global cancer MIR among men was nearly 55%, with variations by cancer types, age, and HDI. The MIR was lowest for thyroid cancer (7.6%) and highest for pancreatic cancer (90.9%); among World Health Organization regions, Africa had the highest MIR (72.6%), while the Americas had the lowest MIR (39.1%); countries with the lowest HDI had the highest MIR (73.5% vs 41.1% for very high HDI).
- Lung cancer was the leading cause for cases and deaths in 2022 and was projected to remain the leading cause in 2050.
IN PRACTICE:
“Disparities in cancer incidence and mortality among men were observed across age groups, countries/territories, and HDI in 2022, with these disparities projected to widen further by 2050,” according to the authors, who called for efforts to “reduce disparities in cancer burden and ensure equity in cancer prevention and care for men across the globe.”
SOURCE:
The study, led by Habtamu Mellie Bizuayehu, PhD, School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, Australia, was published online in Cancer.
LIMITATIONS:
The findings may be influenced by the quality of GLOBOCAN data. Interpretation should be cautious as MIR may not fully reflect cancer outcome inequalities. The study did not include other measures of cancer burden, such as years of life lost or years lived with disability, which were unavailable from the data source.
DISCLOSURES:
The authors did not disclose any funding information. The authors declared no 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 first appeared on Medscape.com.
TOPLINE:
— with substantial disparities in cancer cases and deaths by age and region of the world, a recent analysis found.
METHODOLOGY:
- Overall, men have higher cancer incidence and mortality rates, which can be largely attributed to a higher prevalence of modifiable risk factors such as smoking, alcohol consumption, and occupational carcinogens, as well as the underuse of cancer prevention, screening, and treatment services.
- To assess the burden of cancer in men of different ages and from different regions of the world, researchers analyzed data from the 2022 Global Cancer Observatory (GLOBOCAN), which provides national-level estimates for cancer cases and deaths.
- Study outcomes included the incidence, mortality, and prevalence of cancer among men in 2022, along with projections for 2050. Estimates were stratified by several factors, including age; region; and Human Development Index (HDI), a composite score for health, education, and standard of living.
- Researchers also calculated mortality-to-incidence ratios (MIRs) for various cancer types, where higher values indicate worse survival.
TAKEAWAY:
- The researchers reported an estimated 10.3 million cancer cases and 5.4 million deaths globally in 2022, with almost two thirds of cases and deaths occurring in men aged 65 years or older.
- By 2050, cancer cases and deaths were projected to increase by 84.3% (to 19 million) and 93.2% (to 10.5 million), respectively. The increase from 2022 to 2050 was more than twofold higher for older men and countries with low and medium HDI.
- In 2022, the estimated global cancer MIR among men was nearly 55%, with variations by cancer types, age, and HDI. The MIR was lowest for thyroid cancer (7.6%) and highest for pancreatic cancer (90.9%); among World Health Organization regions, Africa had the highest MIR (72.6%), while the Americas had the lowest MIR (39.1%); countries with the lowest HDI had the highest MIR (73.5% vs 41.1% for very high HDI).
- Lung cancer was the leading cause for cases and deaths in 2022 and was projected to remain the leading cause in 2050.
IN PRACTICE:
“Disparities in cancer incidence and mortality among men were observed across age groups, countries/territories, and HDI in 2022, with these disparities projected to widen further by 2050,” according to the authors, who called for efforts to “reduce disparities in cancer burden and ensure equity in cancer prevention and care for men across the globe.”
SOURCE:
The study, led by Habtamu Mellie Bizuayehu, PhD, School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, Australia, was published online in Cancer.
LIMITATIONS:
The findings may be influenced by the quality of GLOBOCAN data. Interpretation should be cautious as MIR may not fully reflect cancer outcome inequalities. The study did not include other measures of cancer burden, such as years of life lost or years lived with disability, which were unavailable from the data source.
DISCLOSURES:
The authors did not disclose any funding information. The authors declared no 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 first appeared on Medscape.com.
From Scrubs to Social Media: How Some Med Students Become Influencers
A medical student’s life is an endless cycle of classes, exams, clinical rotations, and residency preparation. On TikTok and Instagram, among other sites, they share medical school experiences and lessons learned in the classroom and advocate for causes such as increased diversity and gender rights in the medical field.
This news organization caught up with a few social media influencers with a large online following to learn how medical students can effectively use social media to build a professional brand and network. Most of the students interviewed said that their social media platforms offered an opportunity to educate others about significant medical developments, feel part of a community with a like-minded audience, and network with doctors who may lead them to a future residency or career path.
Many med students said that they built their large audiences by creating a platform for people of their ethnic background, nationality, race, gender, or simply what others weren’t already talking about. They said they saw a niche in social media that was missing or others hadn’t tackled in the same way.
When Joel Bervell began med school in 2020, he questioned some of the lessons he learned about how race is used in medical practice, which didn’t make sense to him. So, he began his own research. He had about 2000 followers on Instagram at the time.
Mr. Bervell read a new study about pulse oximeters and how they often produce misleading readings on patients with dark skin.
He wondered why he hadn’t learned this in medical school, so he posted it on TikTok. Within 24 hours, about 500,000 people viewed it. Most of the comments were from doctors, nurses, and physician assistants who said they weren’t aware of the disparity.
While his initial posts detailed his journey to medical school and a day-in-the-life of a medical student, he transitioned to posts primarily about race, health equity, and what he perceives as racial bias in medicine.
Now, the fourth-year Ghanaian-American student at the Elson S. Floyd College of Medicine at Washington State University Spokane has close to 1.2 million followers on Instagram and TikTok combined. He frequently visits the White House to advise on social media’s influence on healthcare and has appeared on the Kelly Clarkson Show, Good Morning America, CNN, and ABC, among others.
He said he also uses social media to translate complex medical information for a general audience, many of whom access health information online so they can manage their own healthcare. He sees his social media work as an extension of his medical education, allowing him to delve deeper into subjects and report on them as if he were publishing research in a medical journal.
“When I came to medical school, yes, I wanted to be a doctor. But I also wanted to impact people.” Social media allows him to educate many more people than individual patients, the 29-year-old told this news organization.
Inspiring Minorities
Tabhata Paulet, 27, started her TikTok presence as a premed student in 2021. She aimed to provide free resources to help low-income, first-generation Latinx students like herself study for standardized exams.
“I always looked online for guidance and resources, and the medical influencers did not share a similar background. So, I shared my story and what I had to do as a first-generation and first person in my family to become a physician. I did not have access to the same resources as my peers,” said Ms. Paulet, who was born in Peru and came to New Jersey as a child.
Students who are Hispanic, Latinx, or of Spanish origin made up 6.8% of total medical school enrollment in 2023-2024, up slightly from 6.7% in 2022-2023, according to the Association of American Medical Colleges (AAMC).
Ms. Paulet’s online presence grew when she began documenting her experiences as a first-year medical student, bridging the language barrier for Spanish-speaking patients so they could understand their diagnosis and treatment. She often posts about health disparity and barriers to care for underserved communities.
Most of her nearly 22,000 followers are Hispanic, said the now fourth-year student at Rutgers New Jersey Medical School in Newark, New Jersey. “I talk a lot about my interesting Spanish-speaking patients ... and how sometimes speaking their native language truly makes a difference in their care.”
She believes that she serves an important role in social media. “It can be very inspirational for those who come after you [in med school] to see someone from a similar culture and upbringing.”
Creating a Community
It was during a therapy session 4 years ago that Jeremy “JP” Scott decided to share Instagram posts about his experiences as a nontraditional medical student. The 37-year-old was studying at Ross University School of Medicine in Barbados and was feeling lonely as an international medical student training to be a doctor as a second career.
Before starting med school, Mr. Scott was an adjunct professor and lab supervisor at the University of Hartford Biology Department, West Hartford, Connecticut, and then a research assistant and lab manager at the Wistar Institute in Philadelphia.
Although he wanted to follow his mother’s path to becoming a doctor, it was more difficult than he envisioned, said the fourth-year student who completed clinical rotations in the United States and is now applying for residencies.
“I talked about how medical school is not what it appears to be ... There are a lot of challenges we are going through,” especially as people of color, he said.
Mr. Scott believes social media helps people feel included and less alone. He said many of his followers are med students and physicians.
His posts often focus on LGBTQIA+ pride and being a minority as a Black man in medicine.
“The pandemic spurred a lot of us. We had a racial reckoning in our country at the time. It inspired us to talk as Black creators and Black medical students.”
Black or African American medical students made up 8.5% of total med school enrollment in 2023-2024, a slight increase from 2022 to 2023, according to AAMC figures. Black men represented 7% of total enrollment in 2023-2024, while Black women represented 9.8%.
After only a handful of online posts in which Mr. Scott candidly discussed his mental health struggles and relationships, he attracted the attention of several medical apparel companies, including the popular FIGS scrubs. He’s now an ambassador for the company, which supports him and his content.
“My association with FIGS has helped attract a wider online audience, increasing my presence.” Today, he has 14,000 Instagram followers. “It opened up so many opportunities,” Mr. Scott said. One example is working with the national LGBTQIA+ community.
“The goal was never to be a social media influencer, to gain sponsorships or photo opportunities,” he said.
“My job, first, is as a medical student. Everything else is second. I am not trying to be a professional social media personality. I’m trying to be an actual physician.” He also tries to separate JP “social media” from Jeremy, the medical student.
“On Instagram, anyone can pull it up and see what you’re doing. The last thing I want is for them to think that I’m not serious about what I’m doing, that I’m not here to learn and become a doctor.”
Benefits and Drawbacks
Ms. Paulet said her social media following helped her connect with leaders in the Latinx medical community, including an obstetrics anesthesiologist, her intended specialty. “I don’t think I’d be able to do that without a social media platform.”
Her online activity also propelled her from regional to national leadership in the Latino Medical Student Association (LMSA). She now also runs their Instagram page, which has 14,000 followers.
Mr. Bervell believes social media is a great way to network. He’s connected with people he wouldn’t have met otherwise, including physicians. “I think it will help me get into a residency,” he said. “It allows people to know who you are ... They will be able to tell in a few videos the type of doctor I want to be.”
On the other hand, Mr. Bervell is aware of the negative impacts of social media on mental health. “You can get lost in social media.” For that reason, he often tries to disconnect. “I can go days without my phone.”
Posting on social media can be time-consuming, Mr. Bervell admitted. He said he spent about 2 hours a day researching, editing, and posting on TikTok when he first started building his following. Now, he spends about 2-3 hours a week creating videos. “I don’t post every day anymore. I don’t have the time.”
When she started building her TikTok presence, Ms. Paulet said she devoted 15 hours a week to the endeavor, but now she spends 10-12 hours a week posting online, including on LMSA’s Instagram page. “Whenever you are done with an exam or have a study break, this is something fun to do.” She also says you never know who you’re going to inspire when you put yourself out there.
“Talk about your journey, rotations, or your experience in your first or second year of medical school. Talk about milestones like board exams.”
Word to the Wise
Some students may be concerned that their posts might affect a potential residency program. But the medical students interviewed say they want to find programs that align with their values and accept them for who they are.
Mr. Scott said he’s not worried about someone not liking him because of who he is. “I am Black and openly gay. If it’s a problem, I don’t need to work with you or your institution.”
Mr. Bervell stressed that medical students should stay professional online. “I reach 5-10 million people a month, and I have to think: Would I want them to see this? You have to know at all times that someone is watching. I’m very careful about how I post. I script out every video.”
Mr. Scott agreed. He advises those interested in becoming medical influencers to know what they can’t post online. For example, to ensure safety and privacy, Mr. Scott doesn’t take photos in the hospital, show his medical badge, or post patient information. “You want to be respectful of your future medical profession,” he said.
“If it’s something my mother would be ashamed of, I don’t need to post about it.”
A version of this article first appeared on Medscape.com.
A medical student’s life is an endless cycle of classes, exams, clinical rotations, and residency preparation. On TikTok and Instagram, among other sites, they share medical school experiences and lessons learned in the classroom and advocate for causes such as increased diversity and gender rights in the medical field.
This news organization caught up with a few social media influencers with a large online following to learn how medical students can effectively use social media to build a professional brand and network. Most of the students interviewed said that their social media platforms offered an opportunity to educate others about significant medical developments, feel part of a community with a like-minded audience, and network with doctors who may lead them to a future residency or career path.
Many med students said that they built their large audiences by creating a platform for people of their ethnic background, nationality, race, gender, or simply what others weren’t already talking about. They said they saw a niche in social media that was missing or others hadn’t tackled in the same way.
When Joel Bervell began med school in 2020, he questioned some of the lessons he learned about how race is used in medical practice, which didn’t make sense to him. So, he began his own research. He had about 2000 followers on Instagram at the time.
Mr. Bervell read a new study about pulse oximeters and how they often produce misleading readings on patients with dark skin.
He wondered why he hadn’t learned this in medical school, so he posted it on TikTok. Within 24 hours, about 500,000 people viewed it. Most of the comments were from doctors, nurses, and physician assistants who said they weren’t aware of the disparity.
While his initial posts detailed his journey to medical school and a day-in-the-life of a medical student, he transitioned to posts primarily about race, health equity, and what he perceives as racial bias in medicine.
Now, the fourth-year Ghanaian-American student at the Elson S. Floyd College of Medicine at Washington State University Spokane has close to 1.2 million followers on Instagram and TikTok combined. He frequently visits the White House to advise on social media’s influence on healthcare and has appeared on the Kelly Clarkson Show, Good Morning America, CNN, and ABC, among others.
He said he also uses social media to translate complex medical information for a general audience, many of whom access health information online so they can manage their own healthcare. He sees his social media work as an extension of his medical education, allowing him to delve deeper into subjects and report on them as if he were publishing research in a medical journal.
“When I came to medical school, yes, I wanted to be a doctor. But I also wanted to impact people.” Social media allows him to educate many more people than individual patients, the 29-year-old told this news organization.
Inspiring Minorities
Tabhata Paulet, 27, started her TikTok presence as a premed student in 2021. She aimed to provide free resources to help low-income, first-generation Latinx students like herself study for standardized exams.
“I always looked online for guidance and resources, and the medical influencers did not share a similar background. So, I shared my story and what I had to do as a first-generation and first person in my family to become a physician. I did not have access to the same resources as my peers,” said Ms. Paulet, who was born in Peru and came to New Jersey as a child.
Students who are Hispanic, Latinx, or of Spanish origin made up 6.8% of total medical school enrollment in 2023-2024, up slightly from 6.7% in 2022-2023, according to the Association of American Medical Colleges (AAMC).
Ms. Paulet’s online presence grew when she began documenting her experiences as a first-year medical student, bridging the language barrier for Spanish-speaking patients so they could understand their diagnosis and treatment. She often posts about health disparity and barriers to care for underserved communities.
Most of her nearly 22,000 followers are Hispanic, said the now fourth-year student at Rutgers New Jersey Medical School in Newark, New Jersey. “I talk a lot about my interesting Spanish-speaking patients ... and how sometimes speaking their native language truly makes a difference in their care.”
She believes that she serves an important role in social media. “It can be very inspirational for those who come after you [in med school] to see someone from a similar culture and upbringing.”
Creating a Community
It was during a therapy session 4 years ago that Jeremy “JP” Scott decided to share Instagram posts about his experiences as a nontraditional medical student. The 37-year-old was studying at Ross University School of Medicine in Barbados and was feeling lonely as an international medical student training to be a doctor as a second career.
Before starting med school, Mr. Scott was an adjunct professor and lab supervisor at the University of Hartford Biology Department, West Hartford, Connecticut, and then a research assistant and lab manager at the Wistar Institute in Philadelphia.
Although he wanted to follow his mother’s path to becoming a doctor, it was more difficult than he envisioned, said the fourth-year student who completed clinical rotations in the United States and is now applying for residencies.
“I talked about how medical school is not what it appears to be ... There are a lot of challenges we are going through,” especially as people of color, he said.
Mr. Scott believes social media helps people feel included and less alone. He said many of his followers are med students and physicians.
His posts often focus on LGBTQIA+ pride and being a minority as a Black man in medicine.
“The pandemic spurred a lot of us. We had a racial reckoning in our country at the time. It inspired us to talk as Black creators and Black medical students.”
Black or African American medical students made up 8.5% of total med school enrollment in 2023-2024, a slight increase from 2022 to 2023, according to AAMC figures. Black men represented 7% of total enrollment in 2023-2024, while Black women represented 9.8%.
After only a handful of online posts in which Mr. Scott candidly discussed his mental health struggles and relationships, he attracted the attention of several medical apparel companies, including the popular FIGS scrubs. He’s now an ambassador for the company, which supports him and his content.
“My association with FIGS has helped attract a wider online audience, increasing my presence.” Today, he has 14,000 Instagram followers. “It opened up so many opportunities,” Mr. Scott said. One example is working with the national LGBTQIA+ community.
“The goal was never to be a social media influencer, to gain sponsorships or photo opportunities,” he said.
“My job, first, is as a medical student. Everything else is second. I am not trying to be a professional social media personality. I’m trying to be an actual physician.” He also tries to separate JP “social media” from Jeremy, the medical student.
“On Instagram, anyone can pull it up and see what you’re doing. The last thing I want is for them to think that I’m not serious about what I’m doing, that I’m not here to learn and become a doctor.”
Benefits and Drawbacks
Ms. Paulet said her social media following helped her connect with leaders in the Latinx medical community, including an obstetrics anesthesiologist, her intended specialty. “I don’t think I’d be able to do that without a social media platform.”
Her online activity also propelled her from regional to national leadership in the Latino Medical Student Association (LMSA). She now also runs their Instagram page, which has 14,000 followers.
Mr. Bervell believes social media is a great way to network. He’s connected with people he wouldn’t have met otherwise, including physicians. “I think it will help me get into a residency,” he said. “It allows people to know who you are ... They will be able to tell in a few videos the type of doctor I want to be.”
On the other hand, Mr. Bervell is aware of the negative impacts of social media on mental health. “You can get lost in social media.” For that reason, he often tries to disconnect. “I can go days without my phone.”
Posting on social media can be time-consuming, Mr. Bervell admitted. He said he spent about 2 hours a day researching, editing, and posting on TikTok when he first started building his following. Now, he spends about 2-3 hours a week creating videos. “I don’t post every day anymore. I don’t have the time.”
When she started building her TikTok presence, Ms. Paulet said she devoted 15 hours a week to the endeavor, but now she spends 10-12 hours a week posting online, including on LMSA’s Instagram page. “Whenever you are done with an exam or have a study break, this is something fun to do.” She also says you never know who you’re going to inspire when you put yourself out there.
“Talk about your journey, rotations, or your experience in your first or second year of medical school. Talk about milestones like board exams.”
Word to the Wise
Some students may be concerned that their posts might affect a potential residency program. But the medical students interviewed say they want to find programs that align with their values and accept them for who they are.
Mr. Scott said he’s not worried about someone not liking him because of who he is. “I am Black and openly gay. If it’s a problem, I don’t need to work with you or your institution.”
Mr. Bervell stressed that medical students should stay professional online. “I reach 5-10 million people a month, and I have to think: Would I want them to see this? You have to know at all times that someone is watching. I’m very careful about how I post. I script out every video.”
Mr. Scott agreed. He advises those interested in becoming medical influencers to know what they can’t post online. For example, to ensure safety and privacy, Mr. Scott doesn’t take photos in the hospital, show his medical badge, or post patient information. “You want to be respectful of your future medical profession,” he said.
“If it’s something my mother would be ashamed of, I don’t need to post about it.”
A version of this article first appeared on Medscape.com.
A medical student’s life is an endless cycle of classes, exams, clinical rotations, and residency preparation. On TikTok and Instagram, among other sites, they share medical school experiences and lessons learned in the classroom and advocate for causes such as increased diversity and gender rights in the medical field.
This news organization caught up with a few social media influencers with a large online following to learn how medical students can effectively use social media to build a professional brand and network. Most of the students interviewed said that their social media platforms offered an opportunity to educate others about significant medical developments, feel part of a community with a like-minded audience, and network with doctors who may lead them to a future residency or career path.
Many med students said that they built their large audiences by creating a platform for people of their ethnic background, nationality, race, gender, or simply what others weren’t already talking about. They said they saw a niche in social media that was missing or others hadn’t tackled in the same way.
When Joel Bervell began med school in 2020, he questioned some of the lessons he learned about how race is used in medical practice, which didn’t make sense to him. So, he began his own research. He had about 2000 followers on Instagram at the time.
Mr. Bervell read a new study about pulse oximeters and how they often produce misleading readings on patients with dark skin.
He wondered why he hadn’t learned this in medical school, so he posted it on TikTok. Within 24 hours, about 500,000 people viewed it. Most of the comments were from doctors, nurses, and physician assistants who said they weren’t aware of the disparity.
While his initial posts detailed his journey to medical school and a day-in-the-life of a medical student, he transitioned to posts primarily about race, health equity, and what he perceives as racial bias in medicine.
Now, the fourth-year Ghanaian-American student at the Elson S. Floyd College of Medicine at Washington State University Spokane has close to 1.2 million followers on Instagram and TikTok combined. He frequently visits the White House to advise on social media’s influence on healthcare and has appeared on the Kelly Clarkson Show, Good Morning America, CNN, and ABC, among others.
He said he also uses social media to translate complex medical information for a general audience, many of whom access health information online so they can manage their own healthcare. He sees his social media work as an extension of his medical education, allowing him to delve deeper into subjects and report on them as if he were publishing research in a medical journal.
“When I came to medical school, yes, I wanted to be a doctor. But I also wanted to impact people.” Social media allows him to educate many more people than individual patients, the 29-year-old told this news organization.
Inspiring Minorities
Tabhata Paulet, 27, started her TikTok presence as a premed student in 2021. She aimed to provide free resources to help low-income, first-generation Latinx students like herself study for standardized exams.
“I always looked online for guidance and resources, and the medical influencers did not share a similar background. So, I shared my story and what I had to do as a first-generation and first person in my family to become a physician. I did not have access to the same resources as my peers,” said Ms. Paulet, who was born in Peru and came to New Jersey as a child.
Students who are Hispanic, Latinx, or of Spanish origin made up 6.8% of total medical school enrollment in 2023-2024, up slightly from 6.7% in 2022-2023, according to the Association of American Medical Colleges (AAMC).
Ms. Paulet’s online presence grew when she began documenting her experiences as a first-year medical student, bridging the language barrier for Spanish-speaking patients so they could understand their diagnosis and treatment. She often posts about health disparity and barriers to care for underserved communities.
Most of her nearly 22,000 followers are Hispanic, said the now fourth-year student at Rutgers New Jersey Medical School in Newark, New Jersey. “I talk a lot about my interesting Spanish-speaking patients ... and how sometimes speaking their native language truly makes a difference in their care.”
She believes that she serves an important role in social media. “It can be very inspirational for those who come after you [in med school] to see someone from a similar culture and upbringing.”
Creating a Community
It was during a therapy session 4 years ago that Jeremy “JP” Scott decided to share Instagram posts about his experiences as a nontraditional medical student. The 37-year-old was studying at Ross University School of Medicine in Barbados and was feeling lonely as an international medical student training to be a doctor as a second career.
Before starting med school, Mr. Scott was an adjunct professor and lab supervisor at the University of Hartford Biology Department, West Hartford, Connecticut, and then a research assistant and lab manager at the Wistar Institute in Philadelphia.
Although he wanted to follow his mother’s path to becoming a doctor, it was more difficult than he envisioned, said the fourth-year student who completed clinical rotations in the United States and is now applying for residencies.
“I talked about how medical school is not what it appears to be ... There are a lot of challenges we are going through,” especially as people of color, he said.
Mr. Scott believes social media helps people feel included and less alone. He said many of his followers are med students and physicians.
His posts often focus on LGBTQIA+ pride and being a minority as a Black man in medicine.
“The pandemic spurred a lot of us. We had a racial reckoning in our country at the time. It inspired us to talk as Black creators and Black medical students.”
Black or African American medical students made up 8.5% of total med school enrollment in 2023-2024, a slight increase from 2022 to 2023, according to AAMC figures. Black men represented 7% of total enrollment in 2023-2024, while Black women represented 9.8%.
After only a handful of online posts in which Mr. Scott candidly discussed his mental health struggles and relationships, he attracted the attention of several medical apparel companies, including the popular FIGS scrubs. He’s now an ambassador for the company, which supports him and his content.
“My association with FIGS has helped attract a wider online audience, increasing my presence.” Today, he has 14,000 Instagram followers. “It opened up so many opportunities,” Mr. Scott said. One example is working with the national LGBTQIA+ community.
“The goal was never to be a social media influencer, to gain sponsorships or photo opportunities,” he said.
“My job, first, is as a medical student. Everything else is second. I am not trying to be a professional social media personality. I’m trying to be an actual physician.” He also tries to separate JP “social media” from Jeremy, the medical student.
“On Instagram, anyone can pull it up and see what you’re doing. The last thing I want is for them to think that I’m not serious about what I’m doing, that I’m not here to learn and become a doctor.”
Benefits and Drawbacks
Ms. Paulet said her social media following helped her connect with leaders in the Latinx medical community, including an obstetrics anesthesiologist, her intended specialty. “I don’t think I’d be able to do that without a social media platform.”
Her online activity also propelled her from regional to national leadership in the Latino Medical Student Association (LMSA). She now also runs their Instagram page, which has 14,000 followers.
Mr. Bervell believes social media is a great way to network. He’s connected with people he wouldn’t have met otherwise, including physicians. “I think it will help me get into a residency,” he said. “It allows people to know who you are ... They will be able to tell in a few videos the type of doctor I want to be.”
On the other hand, Mr. Bervell is aware of the negative impacts of social media on mental health. “You can get lost in social media.” For that reason, he often tries to disconnect. “I can go days without my phone.”
Posting on social media can be time-consuming, Mr. Bervell admitted. He said he spent about 2 hours a day researching, editing, and posting on TikTok when he first started building his following. Now, he spends about 2-3 hours a week creating videos. “I don’t post every day anymore. I don’t have the time.”
When she started building her TikTok presence, Ms. Paulet said she devoted 15 hours a week to the endeavor, but now she spends 10-12 hours a week posting online, including on LMSA’s Instagram page. “Whenever you are done with an exam or have a study break, this is something fun to do.” She also says you never know who you’re going to inspire when you put yourself out there.
“Talk about your journey, rotations, or your experience in your first or second year of medical school. Talk about milestones like board exams.”
Word to the Wise
Some students may be concerned that their posts might affect a potential residency program. But the medical students interviewed say they want to find programs that align with their values and accept them for who they are.
Mr. Scott said he’s not worried about someone not liking him because of who he is. “I am Black and openly gay. If it’s a problem, I don’t need to work with you or your institution.”
Mr. Bervell stressed that medical students should stay professional online. “I reach 5-10 million people a month, and I have to think: Would I want them to see this? You have to know at all times that someone is watching. I’m very careful about how I post. I script out every video.”
Mr. Scott agreed. He advises those interested in becoming medical influencers to know what they can’t post online. For example, to ensure safety and privacy, Mr. Scott doesn’t take photos in the hospital, show his medical badge, or post patient information. “You want to be respectful of your future medical profession,” he said.
“If it’s something my mother would be ashamed of, I don’t need to post about it.”
A version of this article first appeared on Medscape.com.
No Surprises Act: Private Equity Scores Big in Arbitrations
Four organizations owned by private equity firms — including two provider groups — dominated the No Surprises Act’s disputed bill arbitration process in its first year, filing about 70% of 657,040 cases against insurers in 2023, a new report finds.
The findings, recently published in Health Affairs, suggest that private equity–owned organizations are forcefully challenging insurers about payments for certain kinds of out-of-network care.
Their fighting stance has paid off: The percentage of resolved arbitration cases won by providers jumped from 72% in the first quarter of 2023 to 85% in the last quarter, and they were awarded a median of more than 300% the contracted in-network rates for the services in question.
With many more out-of-network bills disputed by providers than expected, “the system is not working exactly the way it was anticipated when this law was written,” lead author Jack Hoadley, PhD, a research professor emeritus at Georgetown University’s McCourt School of Public Policy, Washington, DC, told this news organization.
And, he said, the public and the federal government may end up paying a price.
Congress passed the No Surprises Act in 2020 and then-President Donald Trump signed it. The landmark bill, which went into effect in 2022, was designed to protect patients from unexpected and often exorbitant “surprise” bills after they received some kinds of out-of-network care.
Now, many types of providers are forbidden from billing patients beyond normal in-network costs. In these cases, health plans and out-of-network providers — who don’t have mutual agreements — must wrangle over payment amounts, which are intended to not exceed inflation-adjusted 2019 median levels.
A binding arbitration process kicks in when a provider and a health plan fail to agree about how much the plan will pay for a service. Then, a third-party arbitrator is called in to make a ruling that’s binding. The process is controversial, and a flurry of lawsuits from providers have challenged it.
The new report, which updates an earlier analysis, examines data about disputed cases from all of 2023.
Of the 657,040 new cases filed in 2023, about 70% came from four private equity-funded organizations: Team Health, SCP Health, Radiology Partners, and Envision, which each provide physician services.
About half of the 2023 cases were from just four states: Texas, Florida, Tennessee, and Georgia. The report says the four organizations are especially active in those states. In contrast, Connecticut, Maryland, Massachusetts, and Washington state each had just 1500 or fewer cases filed last year.
Health plans challenged a third of cases as ineligible, and 22% of all resolved cases were deemed ineligible.
Providers won 80% of resolved challenges in 2023, although it’s not clear how much money they reaped. Still, it’s clear that “in the vast majority of the cases, insurers have to pay larger amounts to the provider,” Dr. Hoadley said.
Radiologists made a median of at least 500% of the in-network rate in their cases. Surgeons and neurologists made even more money — a median of at least 800% of the in-network rate. Overall, providers made 322%-350% of in-network rates, depending on the quarter.
Dr. Hoadley cautioned that only a small percentage of medical payments are disputed. In those cases, “the amount that the insurer offers is accepted, and that’s the end of the story.”
Why are the providers often reaping much more than typical payments for in-network services? It’s “really hard to know,” Dr. Hoadley said. But one factor, he said, may be the fact that providers are able to offer evidence challenging that amounts that insurers say they paid previously: “Hey, when we were in network, we were paid this much.”
It’s not clear whether the dispute-and-arbitration system will cost insurers — and patients — more in the long run. The Congressional Budget Office actually thought the No Surprises Act might lower the growth of premiums slightly and save the federal government money, Dr. Hoadley said, but that could potentially not happen. The flood of litigation also contributes to uncertainty, he said.
Alan Sager, PhD, professor of Health Law, Policy, and Management at Boston University School of Public Health, told this news organization that premiums are bound to rise as insurers react to higher costs. He also expects that providers will question the value of being in-network. “If you’re out-of-network and can obtain much higher payments, why would any doctor or hospital remain in-network, especially since they don’t lose out on patient volume?”
Why are provider groups owned by private equity firms so aggressive at challenging health plans? Loren Adler, a fellow and associate director of the Brookings Institution’s Center on Health Policy, told this news organization that these companies play large roles in fields affected by the No Surprises Act. These include emergency medicine, radiology, and anesthesiology, said Mr. Adler, who’s also studied the No Surprises Act’s dispute/arbitration system.
Mr. Adler added that larger companies “are better suited to deal with technical complexities of this process and spend the sort of upfront money to go through it.”
In the big picture, Mr. Adler said, the new study “raises question of whether Congress at some point wants to try to basically bring prices from the arbitration process back in line with average in-network prices.”
The study was funded by the Commonwealth Fund and Arnold Ventures. Dr. Hoadley, Dr. Sager, and Mr. Adler had no disclosures.
A version of this article first appeared on Medscape.com.
Four organizations owned by private equity firms — including two provider groups — dominated the No Surprises Act’s disputed bill arbitration process in its first year, filing about 70% of 657,040 cases against insurers in 2023, a new report finds.
The findings, recently published in Health Affairs, suggest that private equity–owned organizations are forcefully challenging insurers about payments for certain kinds of out-of-network care.
Their fighting stance has paid off: The percentage of resolved arbitration cases won by providers jumped from 72% in the first quarter of 2023 to 85% in the last quarter, and they were awarded a median of more than 300% the contracted in-network rates for the services in question.
With many more out-of-network bills disputed by providers than expected, “the system is not working exactly the way it was anticipated when this law was written,” lead author Jack Hoadley, PhD, a research professor emeritus at Georgetown University’s McCourt School of Public Policy, Washington, DC, told this news organization.
And, he said, the public and the federal government may end up paying a price.
Congress passed the No Surprises Act in 2020 and then-President Donald Trump signed it. The landmark bill, which went into effect in 2022, was designed to protect patients from unexpected and often exorbitant “surprise” bills after they received some kinds of out-of-network care.
Now, many types of providers are forbidden from billing patients beyond normal in-network costs. In these cases, health plans and out-of-network providers — who don’t have mutual agreements — must wrangle over payment amounts, which are intended to not exceed inflation-adjusted 2019 median levels.
A binding arbitration process kicks in when a provider and a health plan fail to agree about how much the plan will pay for a service. Then, a third-party arbitrator is called in to make a ruling that’s binding. The process is controversial, and a flurry of lawsuits from providers have challenged it.
The new report, which updates an earlier analysis, examines data about disputed cases from all of 2023.
Of the 657,040 new cases filed in 2023, about 70% came from four private equity-funded organizations: Team Health, SCP Health, Radiology Partners, and Envision, which each provide physician services.
About half of the 2023 cases were from just four states: Texas, Florida, Tennessee, and Georgia. The report says the four organizations are especially active in those states. In contrast, Connecticut, Maryland, Massachusetts, and Washington state each had just 1500 or fewer cases filed last year.
Health plans challenged a third of cases as ineligible, and 22% of all resolved cases were deemed ineligible.
Providers won 80% of resolved challenges in 2023, although it’s not clear how much money they reaped. Still, it’s clear that “in the vast majority of the cases, insurers have to pay larger amounts to the provider,” Dr. Hoadley said.
Radiologists made a median of at least 500% of the in-network rate in their cases. Surgeons and neurologists made even more money — a median of at least 800% of the in-network rate. Overall, providers made 322%-350% of in-network rates, depending on the quarter.
Dr. Hoadley cautioned that only a small percentage of medical payments are disputed. In those cases, “the amount that the insurer offers is accepted, and that’s the end of the story.”
Why are the providers often reaping much more than typical payments for in-network services? It’s “really hard to know,” Dr. Hoadley said. But one factor, he said, may be the fact that providers are able to offer evidence challenging that amounts that insurers say they paid previously: “Hey, when we were in network, we were paid this much.”
It’s not clear whether the dispute-and-arbitration system will cost insurers — and patients — more in the long run. The Congressional Budget Office actually thought the No Surprises Act might lower the growth of premiums slightly and save the federal government money, Dr. Hoadley said, but that could potentially not happen. The flood of litigation also contributes to uncertainty, he said.
Alan Sager, PhD, professor of Health Law, Policy, and Management at Boston University School of Public Health, told this news organization that premiums are bound to rise as insurers react to higher costs. He also expects that providers will question the value of being in-network. “If you’re out-of-network and can obtain much higher payments, why would any doctor or hospital remain in-network, especially since they don’t lose out on patient volume?”
Why are provider groups owned by private equity firms so aggressive at challenging health plans? Loren Adler, a fellow and associate director of the Brookings Institution’s Center on Health Policy, told this news organization that these companies play large roles in fields affected by the No Surprises Act. These include emergency medicine, radiology, and anesthesiology, said Mr. Adler, who’s also studied the No Surprises Act’s dispute/arbitration system.
Mr. Adler added that larger companies “are better suited to deal with technical complexities of this process and spend the sort of upfront money to go through it.”
In the big picture, Mr. Adler said, the new study “raises question of whether Congress at some point wants to try to basically bring prices from the arbitration process back in line with average in-network prices.”
The study was funded by the Commonwealth Fund and Arnold Ventures. Dr. Hoadley, Dr. Sager, and Mr. Adler had no disclosures.
A version of this article first appeared on Medscape.com.
Four organizations owned by private equity firms — including two provider groups — dominated the No Surprises Act’s disputed bill arbitration process in its first year, filing about 70% of 657,040 cases against insurers in 2023, a new report finds.
The findings, recently published in Health Affairs, suggest that private equity–owned organizations are forcefully challenging insurers about payments for certain kinds of out-of-network care.
Their fighting stance has paid off: The percentage of resolved arbitration cases won by providers jumped from 72% in the first quarter of 2023 to 85% in the last quarter, and they were awarded a median of more than 300% the contracted in-network rates for the services in question.
With many more out-of-network bills disputed by providers than expected, “the system is not working exactly the way it was anticipated when this law was written,” lead author Jack Hoadley, PhD, a research professor emeritus at Georgetown University’s McCourt School of Public Policy, Washington, DC, told this news organization.
And, he said, the public and the federal government may end up paying a price.
Congress passed the No Surprises Act in 2020 and then-President Donald Trump signed it. The landmark bill, which went into effect in 2022, was designed to protect patients from unexpected and often exorbitant “surprise” bills after they received some kinds of out-of-network care.
Now, many types of providers are forbidden from billing patients beyond normal in-network costs. In these cases, health plans and out-of-network providers — who don’t have mutual agreements — must wrangle over payment amounts, which are intended to not exceed inflation-adjusted 2019 median levels.
A binding arbitration process kicks in when a provider and a health plan fail to agree about how much the plan will pay for a service. Then, a third-party arbitrator is called in to make a ruling that’s binding. The process is controversial, and a flurry of lawsuits from providers have challenged it.
The new report, which updates an earlier analysis, examines data about disputed cases from all of 2023.
Of the 657,040 new cases filed in 2023, about 70% came from four private equity-funded organizations: Team Health, SCP Health, Radiology Partners, and Envision, which each provide physician services.
About half of the 2023 cases were from just four states: Texas, Florida, Tennessee, and Georgia. The report says the four organizations are especially active in those states. In contrast, Connecticut, Maryland, Massachusetts, and Washington state each had just 1500 or fewer cases filed last year.
Health plans challenged a third of cases as ineligible, and 22% of all resolved cases were deemed ineligible.
Providers won 80% of resolved challenges in 2023, although it’s not clear how much money they reaped. Still, it’s clear that “in the vast majority of the cases, insurers have to pay larger amounts to the provider,” Dr. Hoadley said.
Radiologists made a median of at least 500% of the in-network rate in their cases. Surgeons and neurologists made even more money — a median of at least 800% of the in-network rate. Overall, providers made 322%-350% of in-network rates, depending on the quarter.
Dr. Hoadley cautioned that only a small percentage of medical payments are disputed. In those cases, “the amount that the insurer offers is accepted, and that’s the end of the story.”
Why are the providers often reaping much more than typical payments for in-network services? It’s “really hard to know,” Dr. Hoadley said. But one factor, he said, may be the fact that providers are able to offer evidence challenging that amounts that insurers say they paid previously: “Hey, when we were in network, we were paid this much.”
It’s not clear whether the dispute-and-arbitration system will cost insurers — and patients — more in the long run. The Congressional Budget Office actually thought the No Surprises Act might lower the growth of premiums slightly and save the federal government money, Dr. Hoadley said, but that could potentially not happen. The flood of litigation also contributes to uncertainty, he said.
Alan Sager, PhD, professor of Health Law, Policy, and Management at Boston University School of Public Health, told this news organization that premiums are bound to rise as insurers react to higher costs. He also expects that providers will question the value of being in-network. “If you’re out-of-network and can obtain much higher payments, why would any doctor or hospital remain in-network, especially since they don’t lose out on patient volume?”
Why are provider groups owned by private equity firms so aggressive at challenging health plans? Loren Adler, a fellow and associate director of the Brookings Institution’s Center on Health Policy, told this news organization that these companies play large roles in fields affected by the No Surprises Act. These include emergency medicine, radiology, and anesthesiology, said Mr. Adler, who’s also studied the No Surprises Act’s dispute/arbitration system.
Mr. Adler added that larger companies “are better suited to deal with technical complexities of this process and spend the sort of upfront money to go through it.”
In the big picture, Mr. Adler said, the new study “raises question of whether Congress at some point wants to try to basically bring prices from the arbitration process back in line with average in-network prices.”
The study was funded by the Commonwealth Fund and Arnold Ventures. Dr. Hoadley, Dr. Sager, and Mr. Adler had no disclosures.
A version of this article first appeared on Medscape.com.
From Baghdad to Boston: The Making of a Blood Cancer Specialist
Today, she practices hematology at Massachusetts General Hospital, Boston, and is a leading advocate for palliative care in oncology.
In an interview, Dr. El-Jawahri spoke about her journey from Baghdad to Boston and the future of palliative medicine in hematology.
Question: Where did you grow up?
Dr. El-Jawahri: My family is from Baghdad, Iraq, and I was born there. We moved to the States when I was 14. I came to Michigan not speaking a word of English. My parents — my father is a mechanical engineer, and my mom is a computer engineer — chose to live in a very white neighborhood in Farmington Hills, in the suburbs of Detroit. The neighborhood did not have any immigrants or Arab Americans. There are a lot of Arab Americans in Michigan, but they chose for me not to hang out with them early on so that I could learn the language. It was a really good choice.
Question: What happened to your college friend?
Dr. El-Jawahri: She had a brain tumor and ended up receiving intensive care at the end of life. We had a lot of conversations about her wishes and desires, but none of those were honored. Her ending was not something that she wanted, nor did it honor her memory.
Question: What do you think went wrong?
Dr. El-Jawahri: She was getting treatment for her family’s sake. The idea of losing her was too hard for them. I remember vividly the conversations where she would say, “I just hope I don’t end up in the hospital at the end of life.” We had that conversation explicitly. But because we were young, her family was very involved in her care. A lot of the decision-making was very complicated.
Question: How did this experience change your career path?
Dr. El-Jawahri: I went into medicine specifically to become an oncologist and cure cancer. The naive 20-year-old in me said, “Nobody should die this miserable death. I’m going to go in, and I’m going to cure it.”
Question: How did palliative medicine become your major focus?
Dr. El-Jawahri: During my first year at Harvard Medical School, I took a course that’s called “Living With Life-Threatening Illness.” It allows medical students to spend their entire first year getting to know a patient living with a serious illness. We’d spend weekly coffee or lunch breaks with them, where we’d hear about their experiences. After every weekly meeting with a patient, we also had a group meeting with several students and group facilitators to talk about — and process — the interactions we had with patients. I was assigned a woman who was living with metastatic breast cancer. I was also introduced to the field of palliative care and how it helps patients manage complex symptoms and process and cope with a difficult diagnosis. It also cultivates the understanding to make informed decisions about their care. That’s when I knew what I wanted to do for the rest of my life — figure out ways to integrate these palliative and supportive care concepts and improve the lived experience of patients and families within the oncology setting.
Question: What happened next?
Dr. El-Jawahri: When I was a first-year intern, I went to residency at Massachusetts General Hospital. I was on an oncology service and admitted a young college student who was diagnosed with acute myeloid leukemia. She was an athlete, and every time she went up the stairs to her dorm, she was getting very short of breath. She went to a walk-in clinic because when you’re 20 and you’re healthy, you don’t think you need anything. They did some blood work, and 2 hours later, they called her and said, “You probably have leukemia. You need to go to the emergency department immediately.” There she saw an emergency doctor who said, “You will be admitted to the hospital. You have leukemia. I’m calling an oncologist, and you’ll probably have to start chemotherapy within the next day or two.”
Question: What was that experience like for the patient?
Dr. El-Jawahri: I’ve never seen someone so scared. The first question she asked me was about her family, who were from North Carolina. She said, “It feels like everybody thinks that I’m dying. Do you think my family will have time to get here?” They were in a car driving over. This is not a unique story in this population. Unfortunately, these patients experience the most traumatic way of being diagnosed and probably the most traumatic experience in oncology. They’re being abducted into a hospital environment, losing all control and starting immediate therapy. Then, for the first 4-6 weeks, they experience immense toxicity, side effects like nausea, vomiting, diarrhea, and mucositis, where they have painful mouth and throat sores that require intravenous pain medications. This causes real posttraumatic stress. After seeing that woman, I made the decision to work in leukemia and transplants to try to make things a little bit better for these patients.
Question: How did the patient fare?
Dr. El-Jawahri: She actually did great and was cured of her disease. Many of our patients with leukemia, especially younger ones, do well in terms of survival. But they struggle with the trauma of their diagnosis and the distress of the acute treatment period. Even in the curative setting, helping patients to cope with a traumatic diagnosis can have a big impact on their quality of life, how they feel, and their long-term outcomes in terms of psychological stress, depression, anxiety, and posttraumatic stress. But so often, our patients with leukemia are not offered palliative care and supportive care because they’re going to be cured.
Question: What is an important lesson from your research into palliative care in hematology?
Dr. El-Jawahri: We can make things better for patients and families by integrating palliative care clinicians into the care of patients. Patients receiving palliative care are more likely to document their end-of-life preferences and discuss them with their clinicians, and they’re less likely to be hospitalized at the end of life. When you ask patients with cancer where do they want to die, many of patients say, “I want to die at home. I don’t want to be in a hospital.” A lot of the work I’m doing now is focused on creating digital apps with components of palliative care and supportive care interventions. Patients can administer these interventions to themselves and learn how to effectively cope and deal with their illness. Some patients may do well with a digital app, but others may actually need the in-person touch. Some may need a hybrid approach. One of the other future directions for us is thinking about how we optimize supportive care interventions. Which ones do we give to which patient?
Question: Considering all that you’ve learned since college, how do you think your sick friend should have been treated?
Dr. El-Jawahri: She was neither introduced to the term palliative care nor to palliative care specialists. Now the standard of care — especially in patients with advanced cancer — is to integrate palliative care clinicians early in the course of illness. We would have loved for her to have a palliative care clinician who didn’t replace the oncologist but rather helped the patient, family, and oncologist communicate more effectively with one another. We hear all the time from patients who say different things to their oncologist than to their palliative care clinician. It’s not like my friend wasn’t able to communicate with her oncologist. But maybe part of it was that she wanted to not disappoint her oncologist [by ending treatment].
Question: Could you tell me about the research you presented at ASCO 2024 regarding 115 adult patients with acute myeloid leukemia and high-risk myelodysplastic syndrome who were receiving non-intensive chemotherapy?
Dr. El-Jawahri: These patients receive therapy that requires frequent clinic visits and often substantially impairs their quality of life. We know this population often does not engage in any timely discussion with their clinicians about their end-of-life care preferences. This multisite randomized clinical trial assigned patients to receive usual oncology care [with palliative care consultations only upon request] vs to see palliative care clinicians monthly in the outpatient setting and twice weekly every time they were hospitalized. The intervention focused on how to help patients manage their symptoms and end-of-life communication in particular. The primary outcome of the study was time from the documentation of end-of-life care preferences to death.
Question: What did you learn?
Dr. El-Jawahri: This is one of the first studies to highlight the impact of palliative care integration on end-of-life care preferences and discussions and documentation in this population. Patients receiving the palliative care intervention were much more likely to discuss their end-of-life care preferences (96.5% vs 68.4%; P < .001). More importantly, those receiving the intervention had a much longer time from documentation of end-of-life care preferences to death. On average, patients in the palliative care intervention group vs the usual care group had a mean of 41 vs 1.5 days from documentation of their preferences to death (P < .001). In the intervention group, these conversations were happening early enough for patients to plan, talk to their families, and discuss their wishes. In the usual care group, they were happening acutely while these patients were dying. We also learned that patients receiving palliative care intervention were less likely to be hospitalized at the end of life (70.6% vs 91.9%; P = .031) and had better quality of life (138.6 vs 125.5; P = .010).
Question: What’s next for your research in this area?
Dr. El-Jawahri: We are doing a large-scale randomized, comparative effectiveness trial of specialty palliative care vs primary palliative care in 11,150 patients with acute myeloid leukemia across 20 institutions in the United States. We expect results in 2028.
Question: What are you hoping to understand?
Dr. El-Jawahri: We will never have enough specialty palliative care clinicians to take care of all patients with serious illness. As a result, we have to learn how palliative care works: How does it improve outcomes? How do we potentially take what palliative care clinicians do and try to integrate it into regular oncology practice? A lot of the work that I’m excited about now regards what we call primary palliative care. How do we train oncology clinicians to incorporate palliative care skills in their practices so we’re able to better meet the needs of our patients and their families? What we’d love to understand from future research is which patient populations need specialty palliative care and which patients can do just fine with an oncology clinician who has a lot of good palliative care skills integrated into their practice.
Dr. El-Jawahri disclosed consulting for Incyte and Novartis.
A version of this article first appeared on Medscape.com.
Today, she practices hematology at Massachusetts General Hospital, Boston, and is a leading advocate for palliative care in oncology.
In an interview, Dr. El-Jawahri spoke about her journey from Baghdad to Boston and the future of palliative medicine in hematology.
Question: Where did you grow up?
Dr. El-Jawahri: My family is from Baghdad, Iraq, and I was born there. We moved to the States when I was 14. I came to Michigan not speaking a word of English. My parents — my father is a mechanical engineer, and my mom is a computer engineer — chose to live in a very white neighborhood in Farmington Hills, in the suburbs of Detroit. The neighborhood did not have any immigrants or Arab Americans. There are a lot of Arab Americans in Michigan, but they chose for me not to hang out with them early on so that I could learn the language. It was a really good choice.
Question: What happened to your college friend?
Dr. El-Jawahri: She had a brain tumor and ended up receiving intensive care at the end of life. We had a lot of conversations about her wishes and desires, but none of those were honored. Her ending was not something that she wanted, nor did it honor her memory.
Question: What do you think went wrong?
Dr. El-Jawahri: She was getting treatment for her family’s sake. The idea of losing her was too hard for them. I remember vividly the conversations where she would say, “I just hope I don’t end up in the hospital at the end of life.” We had that conversation explicitly. But because we were young, her family was very involved in her care. A lot of the decision-making was very complicated.
Question: How did this experience change your career path?
Dr. El-Jawahri: I went into medicine specifically to become an oncologist and cure cancer. The naive 20-year-old in me said, “Nobody should die this miserable death. I’m going to go in, and I’m going to cure it.”
Question: How did palliative medicine become your major focus?
Dr. El-Jawahri: During my first year at Harvard Medical School, I took a course that’s called “Living With Life-Threatening Illness.” It allows medical students to spend their entire first year getting to know a patient living with a serious illness. We’d spend weekly coffee or lunch breaks with them, where we’d hear about their experiences. After every weekly meeting with a patient, we also had a group meeting with several students and group facilitators to talk about — and process — the interactions we had with patients. I was assigned a woman who was living with metastatic breast cancer. I was also introduced to the field of palliative care and how it helps patients manage complex symptoms and process and cope with a difficult diagnosis. It also cultivates the understanding to make informed decisions about their care. That’s when I knew what I wanted to do for the rest of my life — figure out ways to integrate these palliative and supportive care concepts and improve the lived experience of patients and families within the oncology setting.
Question: What happened next?
Dr. El-Jawahri: When I was a first-year intern, I went to residency at Massachusetts General Hospital. I was on an oncology service and admitted a young college student who was diagnosed with acute myeloid leukemia. She was an athlete, and every time she went up the stairs to her dorm, she was getting very short of breath. She went to a walk-in clinic because when you’re 20 and you’re healthy, you don’t think you need anything. They did some blood work, and 2 hours later, they called her and said, “You probably have leukemia. You need to go to the emergency department immediately.” There she saw an emergency doctor who said, “You will be admitted to the hospital. You have leukemia. I’m calling an oncologist, and you’ll probably have to start chemotherapy within the next day or two.”
Question: What was that experience like for the patient?
Dr. El-Jawahri: I’ve never seen someone so scared. The first question she asked me was about her family, who were from North Carolina. She said, “It feels like everybody thinks that I’m dying. Do you think my family will have time to get here?” They were in a car driving over. This is not a unique story in this population. Unfortunately, these patients experience the most traumatic way of being diagnosed and probably the most traumatic experience in oncology. They’re being abducted into a hospital environment, losing all control and starting immediate therapy. Then, for the first 4-6 weeks, they experience immense toxicity, side effects like nausea, vomiting, diarrhea, and mucositis, where they have painful mouth and throat sores that require intravenous pain medications. This causes real posttraumatic stress. After seeing that woman, I made the decision to work in leukemia and transplants to try to make things a little bit better for these patients.
Question: How did the patient fare?
Dr. El-Jawahri: She actually did great and was cured of her disease. Many of our patients with leukemia, especially younger ones, do well in terms of survival. But they struggle with the trauma of their diagnosis and the distress of the acute treatment period. Even in the curative setting, helping patients to cope with a traumatic diagnosis can have a big impact on their quality of life, how they feel, and their long-term outcomes in terms of psychological stress, depression, anxiety, and posttraumatic stress. But so often, our patients with leukemia are not offered palliative care and supportive care because they’re going to be cured.
Question: What is an important lesson from your research into palliative care in hematology?
Dr. El-Jawahri: We can make things better for patients and families by integrating palliative care clinicians into the care of patients. Patients receiving palliative care are more likely to document their end-of-life preferences and discuss them with their clinicians, and they’re less likely to be hospitalized at the end of life. When you ask patients with cancer where do they want to die, many of patients say, “I want to die at home. I don’t want to be in a hospital.” A lot of the work I’m doing now is focused on creating digital apps with components of palliative care and supportive care interventions. Patients can administer these interventions to themselves and learn how to effectively cope and deal with their illness. Some patients may do well with a digital app, but others may actually need the in-person touch. Some may need a hybrid approach. One of the other future directions for us is thinking about how we optimize supportive care interventions. Which ones do we give to which patient?
Question: Considering all that you’ve learned since college, how do you think your sick friend should have been treated?
Dr. El-Jawahri: She was neither introduced to the term palliative care nor to palliative care specialists. Now the standard of care — especially in patients with advanced cancer — is to integrate palliative care clinicians early in the course of illness. We would have loved for her to have a palliative care clinician who didn’t replace the oncologist but rather helped the patient, family, and oncologist communicate more effectively with one another. We hear all the time from patients who say different things to their oncologist than to their palliative care clinician. It’s not like my friend wasn’t able to communicate with her oncologist. But maybe part of it was that she wanted to not disappoint her oncologist [by ending treatment].
Question: Could you tell me about the research you presented at ASCO 2024 regarding 115 adult patients with acute myeloid leukemia and high-risk myelodysplastic syndrome who were receiving non-intensive chemotherapy?
Dr. El-Jawahri: These patients receive therapy that requires frequent clinic visits and often substantially impairs their quality of life. We know this population often does not engage in any timely discussion with their clinicians about their end-of-life care preferences. This multisite randomized clinical trial assigned patients to receive usual oncology care [with palliative care consultations only upon request] vs to see palliative care clinicians monthly in the outpatient setting and twice weekly every time they were hospitalized. The intervention focused on how to help patients manage their symptoms and end-of-life communication in particular. The primary outcome of the study was time from the documentation of end-of-life care preferences to death.
Question: What did you learn?
Dr. El-Jawahri: This is one of the first studies to highlight the impact of palliative care integration on end-of-life care preferences and discussions and documentation in this population. Patients receiving the palliative care intervention were much more likely to discuss their end-of-life care preferences (96.5% vs 68.4%; P < .001). More importantly, those receiving the intervention had a much longer time from documentation of end-of-life care preferences to death. On average, patients in the palliative care intervention group vs the usual care group had a mean of 41 vs 1.5 days from documentation of their preferences to death (P < .001). In the intervention group, these conversations were happening early enough for patients to plan, talk to their families, and discuss their wishes. In the usual care group, they were happening acutely while these patients were dying. We also learned that patients receiving palliative care intervention were less likely to be hospitalized at the end of life (70.6% vs 91.9%; P = .031) and had better quality of life (138.6 vs 125.5; P = .010).
Question: What’s next for your research in this area?
Dr. El-Jawahri: We are doing a large-scale randomized, comparative effectiveness trial of specialty palliative care vs primary palliative care in 11,150 patients with acute myeloid leukemia across 20 institutions in the United States. We expect results in 2028.
Question: What are you hoping to understand?
Dr. El-Jawahri: We will never have enough specialty palliative care clinicians to take care of all patients with serious illness. As a result, we have to learn how palliative care works: How does it improve outcomes? How do we potentially take what palliative care clinicians do and try to integrate it into regular oncology practice? A lot of the work that I’m excited about now regards what we call primary palliative care. How do we train oncology clinicians to incorporate palliative care skills in their practices so we’re able to better meet the needs of our patients and their families? What we’d love to understand from future research is which patient populations need specialty palliative care and which patients can do just fine with an oncology clinician who has a lot of good palliative care skills integrated into their practice.
Dr. El-Jawahri disclosed consulting for Incyte and Novartis.
A version of this article first appeared on Medscape.com.
Today, she practices hematology at Massachusetts General Hospital, Boston, and is a leading advocate for palliative care in oncology.
In an interview, Dr. El-Jawahri spoke about her journey from Baghdad to Boston and the future of palliative medicine in hematology.
Question: Where did you grow up?
Dr. El-Jawahri: My family is from Baghdad, Iraq, and I was born there. We moved to the States when I was 14. I came to Michigan not speaking a word of English. My parents — my father is a mechanical engineer, and my mom is a computer engineer — chose to live in a very white neighborhood in Farmington Hills, in the suburbs of Detroit. The neighborhood did not have any immigrants or Arab Americans. There are a lot of Arab Americans in Michigan, but they chose for me not to hang out with them early on so that I could learn the language. It was a really good choice.
Question: What happened to your college friend?
Dr. El-Jawahri: She had a brain tumor and ended up receiving intensive care at the end of life. We had a lot of conversations about her wishes and desires, but none of those were honored. Her ending was not something that she wanted, nor did it honor her memory.
Question: What do you think went wrong?
Dr. El-Jawahri: She was getting treatment for her family’s sake. The idea of losing her was too hard for them. I remember vividly the conversations where she would say, “I just hope I don’t end up in the hospital at the end of life.” We had that conversation explicitly. But because we were young, her family was very involved in her care. A lot of the decision-making was very complicated.
Question: How did this experience change your career path?
Dr. El-Jawahri: I went into medicine specifically to become an oncologist and cure cancer. The naive 20-year-old in me said, “Nobody should die this miserable death. I’m going to go in, and I’m going to cure it.”
Question: How did palliative medicine become your major focus?
Dr. El-Jawahri: During my first year at Harvard Medical School, I took a course that’s called “Living With Life-Threatening Illness.” It allows medical students to spend their entire first year getting to know a patient living with a serious illness. We’d spend weekly coffee or lunch breaks with them, where we’d hear about their experiences. After every weekly meeting with a patient, we also had a group meeting with several students and group facilitators to talk about — and process — the interactions we had with patients. I was assigned a woman who was living with metastatic breast cancer. I was also introduced to the field of palliative care and how it helps patients manage complex symptoms and process and cope with a difficult diagnosis. It also cultivates the understanding to make informed decisions about their care. That’s when I knew what I wanted to do for the rest of my life — figure out ways to integrate these palliative and supportive care concepts and improve the lived experience of patients and families within the oncology setting.
Question: What happened next?
Dr. El-Jawahri: When I was a first-year intern, I went to residency at Massachusetts General Hospital. I was on an oncology service and admitted a young college student who was diagnosed with acute myeloid leukemia. She was an athlete, and every time she went up the stairs to her dorm, she was getting very short of breath. She went to a walk-in clinic because when you’re 20 and you’re healthy, you don’t think you need anything. They did some blood work, and 2 hours later, they called her and said, “You probably have leukemia. You need to go to the emergency department immediately.” There she saw an emergency doctor who said, “You will be admitted to the hospital. You have leukemia. I’m calling an oncologist, and you’ll probably have to start chemotherapy within the next day or two.”
Question: What was that experience like for the patient?
Dr. El-Jawahri: I’ve never seen someone so scared. The first question she asked me was about her family, who were from North Carolina. She said, “It feels like everybody thinks that I’m dying. Do you think my family will have time to get here?” They were in a car driving over. This is not a unique story in this population. Unfortunately, these patients experience the most traumatic way of being diagnosed and probably the most traumatic experience in oncology. They’re being abducted into a hospital environment, losing all control and starting immediate therapy. Then, for the first 4-6 weeks, they experience immense toxicity, side effects like nausea, vomiting, diarrhea, and mucositis, where they have painful mouth and throat sores that require intravenous pain medications. This causes real posttraumatic stress. After seeing that woman, I made the decision to work in leukemia and transplants to try to make things a little bit better for these patients.
Question: How did the patient fare?
Dr. El-Jawahri: She actually did great and was cured of her disease. Many of our patients with leukemia, especially younger ones, do well in terms of survival. But they struggle with the trauma of their diagnosis and the distress of the acute treatment period. Even in the curative setting, helping patients to cope with a traumatic diagnosis can have a big impact on their quality of life, how they feel, and their long-term outcomes in terms of psychological stress, depression, anxiety, and posttraumatic stress. But so often, our patients with leukemia are not offered palliative care and supportive care because they’re going to be cured.
Question: What is an important lesson from your research into palliative care in hematology?
Dr. El-Jawahri: We can make things better for patients and families by integrating palliative care clinicians into the care of patients. Patients receiving palliative care are more likely to document their end-of-life preferences and discuss them with their clinicians, and they’re less likely to be hospitalized at the end of life. When you ask patients with cancer where do they want to die, many of patients say, “I want to die at home. I don’t want to be in a hospital.” A lot of the work I’m doing now is focused on creating digital apps with components of palliative care and supportive care interventions. Patients can administer these interventions to themselves and learn how to effectively cope and deal with their illness. Some patients may do well with a digital app, but others may actually need the in-person touch. Some may need a hybrid approach. One of the other future directions for us is thinking about how we optimize supportive care interventions. Which ones do we give to which patient?
Question: Considering all that you’ve learned since college, how do you think your sick friend should have been treated?
Dr. El-Jawahri: She was neither introduced to the term palliative care nor to palliative care specialists. Now the standard of care — especially in patients with advanced cancer — is to integrate palliative care clinicians early in the course of illness. We would have loved for her to have a palliative care clinician who didn’t replace the oncologist but rather helped the patient, family, and oncologist communicate more effectively with one another. We hear all the time from patients who say different things to their oncologist than to their palliative care clinician. It’s not like my friend wasn’t able to communicate with her oncologist. But maybe part of it was that she wanted to not disappoint her oncologist [by ending treatment].
Question: Could you tell me about the research you presented at ASCO 2024 regarding 115 adult patients with acute myeloid leukemia and high-risk myelodysplastic syndrome who were receiving non-intensive chemotherapy?
Dr. El-Jawahri: These patients receive therapy that requires frequent clinic visits and often substantially impairs their quality of life. We know this population often does not engage in any timely discussion with their clinicians about their end-of-life care preferences. This multisite randomized clinical trial assigned patients to receive usual oncology care [with palliative care consultations only upon request] vs to see palliative care clinicians monthly in the outpatient setting and twice weekly every time they were hospitalized. The intervention focused on how to help patients manage their symptoms and end-of-life communication in particular. The primary outcome of the study was time from the documentation of end-of-life care preferences to death.
Question: What did you learn?
Dr. El-Jawahri: This is one of the first studies to highlight the impact of palliative care integration on end-of-life care preferences and discussions and documentation in this population. Patients receiving the palliative care intervention were much more likely to discuss their end-of-life care preferences (96.5% vs 68.4%; P < .001). More importantly, those receiving the intervention had a much longer time from documentation of end-of-life care preferences to death. On average, patients in the palliative care intervention group vs the usual care group had a mean of 41 vs 1.5 days from documentation of their preferences to death (P < .001). In the intervention group, these conversations were happening early enough for patients to plan, talk to their families, and discuss their wishes. In the usual care group, they were happening acutely while these patients were dying. We also learned that patients receiving palliative care intervention were less likely to be hospitalized at the end of life (70.6% vs 91.9%; P = .031) and had better quality of life (138.6 vs 125.5; P = .010).
Question: What’s next for your research in this area?
Dr. El-Jawahri: We are doing a large-scale randomized, comparative effectiveness trial of specialty palliative care vs primary palliative care in 11,150 patients with acute myeloid leukemia across 20 institutions in the United States. We expect results in 2028.
Question: What are you hoping to understand?
Dr. El-Jawahri: We will never have enough specialty palliative care clinicians to take care of all patients with serious illness. As a result, we have to learn how palliative care works: How does it improve outcomes? How do we potentially take what palliative care clinicians do and try to integrate it into regular oncology practice? A lot of the work that I’m excited about now regards what we call primary palliative care. How do we train oncology clinicians to incorporate palliative care skills in their practices so we’re able to better meet the needs of our patients and their families? What we’d love to understand from future research is which patient populations need specialty palliative care and which patients can do just fine with an oncology clinician who has a lot of good palliative care skills integrated into their practice.
Dr. El-Jawahri disclosed consulting for Incyte and Novartis.
A version of this article first appeared on Medscape.com.
Cancer Treatment 101: A Primer for Non-Oncologists
The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.
I’m speaking in generalities, understanding that each cancer and each patient is unique.
Chemotherapy
Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.
Careful, compassionate communication between patient and physician is key. Goals and expectations must be clearly understood.
Organized chemotherapeutic efforts are further categorized as first line, second line, and third line.
First-line treatment. The initial round of recommended chemotherapy for a specific cancer. It is typically considered the most effective treatment for that type and stage of cancer on the basis of current research and clinical trials.
Second-line treatment. This is the treatment used if the first-line chemotherapy doesn’t work as desired. Reasons to switch to second-line chemo include:
- Lack of response (the tumor failed to shrink).
- Progression (the cancer may have grown or spread further).
- Adverse side effects were too severe to continue.
The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.
Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:
- New or different chemotherapy drugs compared with prior lines.
- Surgery to debulk the tumor.
- Radiation for symptom control.
- Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
- Immunotherapy: agents that help the body’s immune system fight cancer cells.
- Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.
The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.
It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.
Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
Interventions to Consider Earlier
In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:
- Molecular testing.
- Palliation.
- Clinical trials.
- Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.
I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.
Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:
- Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
- Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
- Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.
Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.
Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.
Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.
Specific situations where discussing palliative care might be appropriate are:
- Soon after a cancer diagnosis.
- If the patient experiences significant side effects from cancer treatment.
- When considering different treatment options, palliative care can complement those treatments.
- In advanced stages of cancer, to focus on comfort and quality of life.
Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.
In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.
Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.
These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.
Read more about these leading innovations:
SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment
Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working
PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment
Using Live Cells from Patients to Find the Right Cancer Drug
Other innovative therapies under investigation could even be agnostic to cancer type:
Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?
High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells
All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions
Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.
Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.
I’m speaking in generalities, understanding that each cancer and each patient is unique.
Chemotherapy
Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.
Careful, compassionate communication between patient and physician is key. Goals and expectations must be clearly understood.
Organized chemotherapeutic efforts are further categorized as first line, second line, and third line.
First-line treatment. The initial round of recommended chemotherapy for a specific cancer. It is typically considered the most effective treatment for that type and stage of cancer on the basis of current research and clinical trials.
Second-line treatment. This is the treatment used if the first-line chemotherapy doesn’t work as desired. Reasons to switch to second-line chemo include:
- Lack of response (the tumor failed to shrink).
- Progression (the cancer may have grown or spread further).
- Adverse side effects were too severe to continue.
The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.
Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:
- New or different chemotherapy drugs compared with prior lines.
- Surgery to debulk the tumor.
- Radiation for symptom control.
- Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
- Immunotherapy: agents that help the body’s immune system fight cancer cells.
- Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.
The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.
It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.
Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
Interventions to Consider Earlier
In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:
- Molecular testing.
- Palliation.
- Clinical trials.
- Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.
I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.
Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:
- Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
- Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
- Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.
Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.
Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.
Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.
Specific situations where discussing palliative care might be appropriate are:
- Soon after a cancer diagnosis.
- If the patient experiences significant side effects from cancer treatment.
- When considering different treatment options, palliative care can complement those treatments.
- In advanced stages of cancer, to focus on comfort and quality of life.
Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.
In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.
Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.
These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.
Read more about these leading innovations:
SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment
Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working
PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment
Using Live Cells from Patients to Find the Right Cancer Drug
Other innovative therapies under investigation could even be agnostic to cancer type:
Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?
High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells
All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions
Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.
Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.
I’m speaking in generalities, understanding that each cancer and each patient is unique.
Chemotherapy
Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.
Careful, compassionate communication between patient and physician is key. Goals and expectations must be clearly understood.
Organized chemotherapeutic efforts are further categorized as first line, second line, and third line.
First-line treatment. The initial round of recommended chemotherapy for a specific cancer. It is typically considered the most effective treatment for that type and stage of cancer on the basis of current research and clinical trials.
Second-line treatment. This is the treatment used if the first-line chemotherapy doesn’t work as desired. Reasons to switch to second-line chemo include:
- Lack of response (the tumor failed to shrink).
- Progression (the cancer may have grown or spread further).
- Adverse side effects were too severe to continue.
The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.
Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:
- New or different chemotherapy drugs compared with prior lines.
- Surgery to debulk the tumor.
- Radiation for symptom control.
- Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
- Immunotherapy: agents that help the body’s immune system fight cancer cells.
- Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.
The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.
It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.
Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
Interventions to Consider Earlier
In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:
- Molecular testing.
- Palliation.
- Clinical trials.
- Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.
I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.
Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:
- Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
- Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
- Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.
Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.
Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.
Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.
Specific situations where discussing palliative care might be appropriate are:
- Soon after a cancer diagnosis.
- If the patient experiences significant side effects from cancer treatment.
- When considering different treatment options, palliative care can complement those treatments.
- In advanced stages of cancer, to focus on comfort and quality of life.
Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.
In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.
Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.
These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.
Read more about these leading innovations:
SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment
Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working
PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment
Using Live Cells from Patients to Find the Right Cancer Drug
Other innovative therapies under investigation could even be agnostic to cancer type:
Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?
High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells
All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions
Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.
Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Physicians Lament Over Reliance on Relative Value Units: Survey
Most physicians oppose the way standardized relative value units (RVUs) are used to determine performance and compensation, according to Medscape’s 2024 Physicians and RVUs Report. About 6 in 10 survey respondents were unhappy with how RVUs affected them financially, while 7 in 10 said RVUs were poor measures of productivity.
The report analyzed 2024 survey data from 1005 practicing physicians who earn RVUs.
“I’m already mad that the medical field is controlled by health insurers and what they pay and authorize,” said an anesthesiologist in New York. “Then [that approach] is transferred to medical offices and hospitals, where physicians are paid by RVUs.”
Most physicians surveyed produced between 4000 and 8000 RVUs per year. Roughly one in six were high RVU generators, generating more than 10,000 annually.
In most cases, the metric influences earning potential — 42% of doctors surveyed said RVUs affect their salaries to some degree. One quarter said their salary was based entirely on RVUs. More than three fourths of physicians who received performance bonuses said they must meet RVU targets to do so.
“The current RVU system encourages unnecessary procedures, hurting patients,” said an orthopedic surgeon in Maine.
Nearly three fourths of practitioners surveyed said they occasionally to frequently felt pressure to take on more patients as a result of this system.
“I know numerous primary care doctors and specialists who have been forced to increase patient volume to meet RVU goals, and none is happy about it,” said Alok Patel, MD, a pediatric hospitalist with Stanford Hospital in Palo Alto, California. “Plus, patients are definitely not happy about being rushed.”
More than half of respondents said they occasionally or frequently felt compelled by their employer to use higher-level coding, which interferes with a physician’s ethical responsibility to the patient, said Arthur L. Caplan, PhD, a bioethicist at NYU Langone Medical Center in New York City.
“Rather than rewarding excellence or good outcomes, you’re kind of rewarding procedures and volume,” said Dr. Caplan. “It’s more than pressure; it’s expected.”
Nearly 6 in 10 physicians said that the method for calculating reimbursements was unfair. Almost half said that they weren’t happy with how their workplace uses RVUs.
A few respondents said that their RVU model, which is often based on what Dr. Patel called an “overly complicated algorithm,” did not account for the time spent on tasks or the fact that some patients miss appointments. RVUs also rely on factors outside the control of a physician, such as location and patient volume, said one doctor.
The model can also lower the level of care patients receive, Dr. Patel said.
“I know primary care doctors who work in RVU-based systems and simply cannot take the necessary time — even if it’s 30-45 minutes — to thoroughly assess a patient, when the model forces them to take on 15-minute encounters.”
Finally, over half of clinicians said alternatives to the RVU system would be more effective, and 77% suggested including qualitative data. One respondent recommended incorporating time spent doing paperwork and communicating with patients, complexity of conditions, and medication management.
A version of this article first appeared on Medscape.com.
Most physicians oppose the way standardized relative value units (RVUs) are used to determine performance and compensation, according to Medscape’s 2024 Physicians and RVUs Report. About 6 in 10 survey respondents were unhappy with how RVUs affected them financially, while 7 in 10 said RVUs were poor measures of productivity.
The report analyzed 2024 survey data from 1005 practicing physicians who earn RVUs.
“I’m already mad that the medical field is controlled by health insurers and what they pay and authorize,” said an anesthesiologist in New York. “Then [that approach] is transferred to medical offices and hospitals, where physicians are paid by RVUs.”
Most physicians surveyed produced between 4000 and 8000 RVUs per year. Roughly one in six were high RVU generators, generating more than 10,000 annually.
In most cases, the metric influences earning potential — 42% of doctors surveyed said RVUs affect their salaries to some degree. One quarter said their salary was based entirely on RVUs. More than three fourths of physicians who received performance bonuses said they must meet RVU targets to do so.
“The current RVU system encourages unnecessary procedures, hurting patients,” said an orthopedic surgeon in Maine.
Nearly three fourths of practitioners surveyed said they occasionally to frequently felt pressure to take on more patients as a result of this system.
“I know numerous primary care doctors and specialists who have been forced to increase patient volume to meet RVU goals, and none is happy about it,” said Alok Patel, MD, a pediatric hospitalist with Stanford Hospital in Palo Alto, California. “Plus, patients are definitely not happy about being rushed.”
More than half of respondents said they occasionally or frequently felt compelled by their employer to use higher-level coding, which interferes with a physician’s ethical responsibility to the patient, said Arthur L. Caplan, PhD, a bioethicist at NYU Langone Medical Center in New York City.
“Rather than rewarding excellence or good outcomes, you’re kind of rewarding procedures and volume,” said Dr. Caplan. “It’s more than pressure; it’s expected.”
Nearly 6 in 10 physicians said that the method for calculating reimbursements was unfair. Almost half said that they weren’t happy with how their workplace uses RVUs.
A few respondents said that their RVU model, which is often based on what Dr. Patel called an “overly complicated algorithm,” did not account for the time spent on tasks or the fact that some patients miss appointments. RVUs also rely on factors outside the control of a physician, such as location and patient volume, said one doctor.
The model can also lower the level of care patients receive, Dr. Patel said.
“I know primary care doctors who work in RVU-based systems and simply cannot take the necessary time — even if it’s 30-45 minutes — to thoroughly assess a patient, when the model forces them to take on 15-minute encounters.”
Finally, over half of clinicians said alternatives to the RVU system would be more effective, and 77% suggested including qualitative data. One respondent recommended incorporating time spent doing paperwork and communicating with patients, complexity of conditions, and medication management.
A version of this article first appeared on Medscape.com.
Most physicians oppose the way standardized relative value units (RVUs) are used to determine performance and compensation, according to Medscape’s 2024 Physicians and RVUs Report. About 6 in 10 survey respondents were unhappy with how RVUs affected them financially, while 7 in 10 said RVUs were poor measures of productivity.
The report analyzed 2024 survey data from 1005 practicing physicians who earn RVUs.
“I’m already mad that the medical field is controlled by health insurers and what they pay and authorize,” said an anesthesiologist in New York. “Then [that approach] is transferred to medical offices and hospitals, where physicians are paid by RVUs.”
Most physicians surveyed produced between 4000 and 8000 RVUs per year. Roughly one in six were high RVU generators, generating more than 10,000 annually.
In most cases, the metric influences earning potential — 42% of doctors surveyed said RVUs affect their salaries to some degree. One quarter said their salary was based entirely on RVUs. More than three fourths of physicians who received performance bonuses said they must meet RVU targets to do so.
“The current RVU system encourages unnecessary procedures, hurting patients,” said an orthopedic surgeon in Maine.
Nearly three fourths of practitioners surveyed said they occasionally to frequently felt pressure to take on more patients as a result of this system.
“I know numerous primary care doctors and specialists who have been forced to increase patient volume to meet RVU goals, and none is happy about it,” said Alok Patel, MD, a pediatric hospitalist with Stanford Hospital in Palo Alto, California. “Plus, patients are definitely not happy about being rushed.”
More than half of respondents said they occasionally or frequently felt compelled by their employer to use higher-level coding, which interferes with a physician’s ethical responsibility to the patient, said Arthur L. Caplan, PhD, a bioethicist at NYU Langone Medical Center in New York City.
“Rather than rewarding excellence or good outcomes, you’re kind of rewarding procedures and volume,” said Dr. Caplan. “It’s more than pressure; it’s expected.”
Nearly 6 in 10 physicians said that the method for calculating reimbursements was unfair. Almost half said that they weren’t happy with how their workplace uses RVUs.
A few respondents said that their RVU model, which is often based on what Dr. Patel called an “overly complicated algorithm,” did not account for the time spent on tasks or the fact that some patients miss appointments. RVUs also rely on factors outside the control of a physician, such as location and patient volume, said one doctor.
The model can also lower the level of care patients receive, Dr. Patel said.
“I know primary care doctors who work in RVU-based systems and simply cannot take the necessary time — even if it’s 30-45 minutes — to thoroughly assess a patient, when the model forces them to take on 15-minute encounters.”
Finally, over half of clinicians said alternatives to the RVU system would be more effective, and 77% suggested including qualitative data. One respondent recommended incorporating time spent doing paperwork and communicating with patients, complexity of conditions, and medication management.
A version of this article first appeared on Medscape.com.