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A Banned Chemical That Is Still Causing Cancer
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Active Surveillance for Cancer Doesn’t Increase Malpractice Risk
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
Few Childhood Cancer Survivors Get Recommended Screenings
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Among childhood cancer survivors in Ontario, Canada, who faced an elevated risk due to chemotherapy or radiation treatments, 53% followed screening recommendations for cardiomyopathy, 13% met colorectal cancer screening guidelines, and 6% adhered to breast cancer screening guidelines.
“Although over 80% of children newly diagnosed with cancer will become long-term survivors, as many as four out of five of these survivors will develop a serious or life-threatening late effect of their cancer therapy by age 45,” lead author Jennifer Shuldiner, PhD, MPH, a scientist at Women’s College Hospital Institute for Health Systems Solutions and Virtual Care in Toronto, told this news organization.
For instance, the risk for colorectal cancer in childhood cancer survivors is two to three times higher than it is among the general population, and the risk for breast cancer is similar between those who underwent chest radiation and those with a BRCA mutation. As many as 50% of those who received anthracycline chemotherapy or radiation involving the heart later develop cardiotoxicity.
The North American Children’s Oncology Group has published long-term follow-up guidelines for survivors of childhood cancer, yet many survivors don’t follow them because of lack of awareness or other barriers, said Dr. Shuldiner.
“Prior research has shown that many survivors do not complete these recommended tests,” she said. “With better knowledge of this at-risk population, we can design, test, and implement appropriate interventions and supports to tackle the issues.”
The study was published online on March 11 in CMAJ.
Changes in Adherence
The researchers conducted a retrospective population-based cohort study analyzing Ontario healthcare administrative data for adult survivors of childhood cancer diagnosed between 1986 and 2014 who faced an elevated risk for therapy-related colorectal cancer, breast cancer, or cardiomyopathy. The research team then assessed long-term adherence to the North American Children’s Oncology Group guidelines and predictors of adherence.
Among 3241 survivors, 3205 (99%) were at elevated risk for cardiomyopathy, 327 (10%) were at elevated risk for colorectal cancer, and 234 (7%) were at elevated risk for breast cancer. In addition, 2806 (87%) were at risk for one late effect, 345 (11%) were at risk for two late effects, and 90 (3%) were at risk for three late effects.
Overall, 53%, 13%, and 6% were adherent to their recommended surveillance for cardiomyopathy, colorectal cancer, and breast cancer, respectively. Over time, adherence increased for colorectal cancer and cardiomyopathy but decreased for breast cancer.
In addition, patients who were older at diagnosis were more likely to follow screening guidelines for colorectal and breast cancers, whereas those who were younger at diagnosis were more likely to follow screening guidelines for cardiomyopathy.
During a median follow-up of 7.8 years, the proportion of time spent adherent was 43% for cardiomyopathy, 14% for colorectal cancer, and 10% for breast cancer.
Survivors who attended a long-term follow-up clinic in the previous year had low adherence rates as well, though they were higher than in the rest of the cohort. In this group, the proportion of time that was spent adherent was 71% for cardiomyopathy, 27% for colorectal cancer, and 15% for breast cancer.
Shuldiner and colleagues are launching a research trial to determine whether a provincial support system can help childhood cancer survivors receive the recommended surveillance. The support system provides information about screening recommendations to survivors as well as reminders and sends key information to their family doctors.
“We now understand that childhood cancer survivors need help to complete the recommended tests,” said Dr. Shuldiner. “If the trial is successful, we hope it will be implemented in Ontario.”
Survivorship Care Plans
Low screening rates may result from a lack of awareness about screening recommendations and the negative long-term effects of cancer treatments, the study authors wrote. Cancer survivors, caregivers, family physicians, specialists, and survivor support groups can share the responsibility of spreading awareness and adhering to guidelines, they noted. In some cases, a survivorship care plan (SCP) may help.
“SCPs are intended to improve adherence by providing follow-up information and facilitating the transition from cancer treatment to survivorship and from pediatric to adult care,” Adam Yan, MD, a staff oncologist and oncology informatics lead at the Hospital for Sick Children in Toronto, told this news organization.
Dr. Yan, who wasn’t involved with this study, has researched surveillance adherence for secondary cancers and cardiac dysfunction among childhood cancer survivors. He and his colleagues found that screening rates were typically low among survivors who faced high risks for cardiac dysfunction and breast, colorectal, or skin cancers.
However, having a survivorship care plan seemed to help, and survivors treated after 1990 were more likely to have an SCP.
“SCP possession by high-risk survivors was associated with increased breast, skin, and cardiac surveillance,” he said. “It is uncertain whether SCP possession leads to adherence or whether SCP possession is a marker of survivors who are focused on their health and thus likely to adhere to preventive health practices, including surveillance.”
The study was funded by the Canadian Institutes of Health Research and ICES, which receives support from the Ontario Ministry of Health and the Ministry of Long-Term Care. Dr. Shuldiner received a Canadian Institutes of Health Research Health System Impact Postdoctoral Fellowship in support of the work. Dr. Yan disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Most Cancer Trial Centers Located Closer to White, Affluent Populations
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
This inequity may be potentiating the underrepresentation of racially minoritized and socioeconomically disadvantaged populations in clinical trials, suggesting that employment of satellite hospitals is needed to expand access to investigational therapies, reported lead author Hassal Lee, MD, PhD, of Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, and colleagues.
“Minoritized and socioeconomically disadvantaged populations are underrepresented in clinical trials,” the investigators wrote in JAMA Oncology. “This may reduce the generalizability of trial results and propagate health disparities. Contributors to inequitable trial participation include individual-level factors and structural factors.”
Specifically, travel time to trial centers, as well as socioeconomic deprivation, can reduce likelihood of trial participation.
“Data on these parameters and population data on self-identified race exist, but their interrelation with clinical research facilities has not been systematically analyzed,” they wrote.
To try to draw comparisons between the distribution of patients of different races and socioeconomic statuses and the locations of clinical research facilities, Dr. Lee and colleagues aggregated data from the US Census, National Trial registry, Nature Index of Cancer Research Health Institutions, OpenStreetMap, National Cancer Institute–designated Cancer Centers list, and National Homeland Infrastructure Foundation. They then characterized catchment population demographics within 30-, 60-, and 120-minute driving commute times of all US hospitals, along with a more focused look at centers capable of conducting phase 1, phase 2, and phase 3 trials.
These efforts revealed broad geographic inequity.The 78 major centers that conduct 94% of all US cancer trials are located within 30 minutes of populations that have a 10.1% higher proportion of self-identified White individuals than the average US county, and a median income $18,900 higher than average (unpaired mean differences).
The publication also includes several maps characterizing racial and socioeconomic demographics within various catchment areas. For example, centers in New York City, Houston, and Chicago have the most diverse catchment populations within a 30-minute commute. Maps of all cities in the United States with populations greater than 500,000 are available in a supplementary index.
“This study indicates that geographical population distributions may present barriers to equitable clinical trial access and that data are available to proactively strategize about reduction of such barriers,” Dr. Lee and colleagues wrote.
The findings call attention to modifiable socioeconomic factors associated with trial participation, they added, like financial toxicity and affordable transportation, noting that ethnic and racial groups consent to trials at similar rates after controlling for income.
In addition, Dr. Lee and colleagues advised clinical trial designers to enlist satellite hospitals to increase participant diversity, since long commutes exacerbate “socioeconomic burdens associated with clinical trial participation,” with trial participation decreasing as commute time increases.
“Existing clinical trial centers may build collaborative efforts with nearby hospitals closer to underrepresented populations or set up community centers to support new collaborative networks to improve geographical access equity,” they wrote. “Methodologically, our approach is transferable to any country, region, or global effort with sufficient source data and can inform decision-making along the continuum of cancer care, from screening to implementing specialist care.”
A coauthor disclosed relationships with Flagship Therapeutics, Leidos Holding Ltd, Pershing Square Foundation, and others.
FROM JAMA ONCOLOGY
Secondary Cancers Post CAR T Therapy: A Concern?
TOPLINE:
METHODOLOGY:
- In November 2023, the FDA announced its investigation into whether chimeric antigen receptor (CAR) T-cell immunotherapies can cause secondary blood cancers, specifically T-cell malignancies. At the time, the agency said: “Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T-cell malignancy with serious outcomes.”
- In January 2024, the FDA issued boxed warnings on the six approved CART cell therapies, citing the possibility of second primary malignancies, including CAR-positive lymphomas, in patients who had received a CAR T agent.
- To evaluate the extent of these secondary cancers, researchers analyzed the FDA Adverse Event Reporting System database for CAR T-cell reports citing second primary malignancies.
TAKEAWAY:
- Overall, the authors identified 12,394 unique adverse events associated with CAR T therapy; of these, 536 adverse events (4.3%) were second primary malignancies.
- Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) accounted for most of the second primary malignancies reports — 51.7% (277 of 536 patients) for axi-cel and 33% (177 of 536 patients) for tis-cel.
- The researchers identified 19 cases of T-cell malignancies, representing only 0.15% of all unique adverse events and 3.54% of all second primary malignancies (19 of 536 patients); 17 of these cases were T-cell non-Hodgkin lymphomas, and two were T-cell large granular lymphocytic leukemia.
- Among the reported 536 second primary malignancies, the most frequent cancers were leukemias (333 reports, or 62%), followed by skin neoplasms (54 reports, or 10.1%), hematopoietic neoplasms excluding leukemias and lymphomas (26 reports, 4.85%), nervous system tumors (21 reports, 3.92%), and respiratory neoplasms (20 reports, 3.73%).
IN PRACTICE:
“We will continue to monitor the data released by the FDA to learn more about CAR T-associated risks. However, it’s crucial to stress that the benefits of CAR T-cell therapies still outweigh the risks for the approved indications,” Magdi Elsallab, MD, the study’s co-lead author, said in a news release.
SOURCE:
This work, led by Dr. Elsallab from Harvard Medical School in Boston, was published online on March 14 in Blood.
LIMITATIONS:
The limitations of the analysis include the presence of duplicate report submissions, incomplete data, difficulty establishing causal relationships, and the potential for both underreporting and overreporting based on the severity of adverse events. Furthermore, without the total number of prescribed products, it was difficult to determine the adverse event frequency.
DISCLOSURES:
The study funding source was not disclosed. Some of the authors reported financial ties with various organizations outside this work, including Bristol Myers Squibb, Janssen Biotech, Johnson & Johnson, Kite Pharma, and Novartis.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- In November 2023, the FDA announced its investigation into whether chimeric antigen receptor (CAR) T-cell immunotherapies can cause secondary blood cancers, specifically T-cell malignancies. At the time, the agency said: “Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T-cell malignancy with serious outcomes.”
- In January 2024, the FDA issued boxed warnings on the six approved CART cell therapies, citing the possibility of second primary malignancies, including CAR-positive lymphomas, in patients who had received a CAR T agent.
- To evaluate the extent of these secondary cancers, researchers analyzed the FDA Adverse Event Reporting System database for CAR T-cell reports citing second primary malignancies.
TAKEAWAY:
- Overall, the authors identified 12,394 unique adverse events associated with CAR T therapy; of these, 536 adverse events (4.3%) were second primary malignancies.
- Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) accounted for most of the second primary malignancies reports — 51.7% (277 of 536 patients) for axi-cel and 33% (177 of 536 patients) for tis-cel.
- The researchers identified 19 cases of T-cell malignancies, representing only 0.15% of all unique adverse events and 3.54% of all second primary malignancies (19 of 536 patients); 17 of these cases were T-cell non-Hodgkin lymphomas, and two were T-cell large granular lymphocytic leukemia.
- Among the reported 536 second primary malignancies, the most frequent cancers were leukemias (333 reports, or 62%), followed by skin neoplasms (54 reports, or 10.1%), hematopoietic neoplasms excluding leukemias and lymphomas (26 reports, 4.85%), nervous system tumors (21 reports, 3.92%), and respiratory neoplasms (20 reports, 3.73%).
IN PRACTICE:
“We will continue to monitor the data released by the FDA to learn more about CAR T-associated risks. However, it’s crucial to stress that the benefits of CAR T-cell therapies still outweigh the risks for the approved indications,” Magdi Elsallab, MD, the study’s co-lead author, said in a news release.
SOURCE:
This work, led by Dr. Elsallab from Harvard Medical School in Boston, was published online on March 14 in Blood.
LIMITATIONS:
The limitations of the analysis include the presence of duplicate report submissions, incomplete data, difficulty establishing causal relationships, and the potential for both underreporting and overreporting based on the severity of adverse events. Furthermore, without the total number of prescribed products, it was difficult to determine the adverse event frequency.
DISCLOSURES:
The study funding source was not disclosed. Some of the authors reported financial ties with various organizations outside this work, including Bristol Myers Squibb, Janssen Biotech, Johnson & Johnson, Kite Pharma, and Novartis.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- In November 2023, the FDA announced its investigation into whether chimeric antigen receptor (CAR) T-cell immunotherapies can cause secondary blood cancers, specifically T-cell malignancies. At the time, the agency said: “Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T-cell malignancy with serious outcomes.”
- In January 2024, the FDA issued boxed warnings on the six approved CART cell therapies, citing the possibility of second primary malignancies, including CAR-positive lymphomas, in patients who had received a CAR T agent.
- To evaluate the extent of these secondary cancers, researchers analyzed the FDA Adverse Event Reporting System database for CAR T-cell reports citing second primary malignancies.
TAKEAWAY:
- Overall, the authors identified 12,394 unique adverse events associated with CAR T therapy; of these, 536 adverse events (4.3%) were second primary malignancies.
- Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) accounted for most of the second primary malignancies reports — 51.7% (277 of 536 patients) for axi-cel and 33% (177 of 536 patients) for tis-cel.
- The researchers identified 19 cases of T-cell malignancies, representing only 0.15% of all unique adverse events and 3.54% of all second primary malignancies (19 of 536 patients); 17 of these cases were T-cell non-Hodgkin lymphomas, and two were T-cell large granular lymphocytic leukemia.
- Among the reported 536 second primary malignancies, the most frequent cancers were leukemias (333 reports, or 62%), followed by skin neoplasms (54 reports, or 10.1%), hematopoietic neoplasms excluding leukemias and lymphomas (26 reports, 4.85%), nervous system tumors (21 reports, 3.92%), and respiratory neoplasms (20 reports, 3.73%).
IN PRACTICE:
“We will continue to monitor the data released by the FDA to learn more about CAR T-associated risks. However, it’s crucial to stress that the benefits of CAR T-cell therapies still outweigh the risks for the approved indications,” Magdi Elsallab, MD, the study’s co-lead author, said in a news release.
SOURCE:
This work, led by Dr. Elsallab from Harvard Medical School in Boston, was published online on March 14 in Blood.
LIMITATIONS:
The limitations of the analysis include the presence of duplicate report submissions, incomplete data, difficulty establishing causal relationships, and the potential for both underreporting and overreporting based on the severity of adverse events. Furthermore, without the total number of prescribed products, it was difficult to determine the adverse event frequency.
DISCLOSURES:
The study funding source was not disclosed. Some of the authors reported financial ties with various organizations outside this work, including Bristol Myers Squibb, Janssen Biotech, Johnson & Johnson, Kite Pharma, and Novartis.
A version of this article appeared on Medscape.com.
FDA Approves Ponatinib for Upfront Ph+ ALL
The approval makes the third-generation tyrosine kinase inhibitor (TKI) the first targeted treatment approved for upfront use in adults with Ph+ ALL, Takeda said in a press release.
Ponatinib was previously approved as monotherapy for Ph+ ALL when no other kinase inhibitors are indicated or for T315I-positive Ph+ ALL, as well as for chronic myeloid leukemia.
Approval for the new indication was based on the PhALLCON trial. In the trial, 245 patients were randomized 2:1 to either ponatinib 30 mg once daily or the first-generation TKI imatinib (Gleevec, Novartis) 600 mg once daily on a chemotherapy background consisting of three cycles of vincristine/dexamethasone induction, six cycles methotrexate/cytarabine consolidation, and 11 cycles of vincristine/prednisone maintenance.
At the end of induction, 12% of patients in the imatinib arm vs 30% in the ponatinib group were in complete remission with no minimal residual disease. Event-free survival data are not yet mature.
At the 2023 American Society of Clinical Oncology annual meeting, an investigator on the trial said that ponatinib plus low-intensity chemotherapy has the potential to become the new standard of care for upfront Ph+ All. However, continued approval for the new indication may depend on trials confirming clinical benefit, Takeda said.
Ponatinib carries a boxed warning of arterial occlusive events, venous thromboembolic events, heart failure, and hepatotoxicity.
The most common adverse reactions reported in the PhALLCON trial were hepatic dysfunction, arthralgia, rash, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/elevated lipase, peripheral neuropathy, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias.
The recommended ponatinib dose is 30 mg orally once daily until the end of induction, dropping down to 15 mg once daily in patients who go into remission with no minimal residual disease after induction, for up to 20 cycles or until loss of response or unacceptable toxicity.
Thirty tablets of 30 mg or 15 mg cost $21,944.54, according to Drugs.com.
A version of this article appeared on Medscape.com.
The approval makes the third-generation tyrosine kinase inhibitor (TKI) the first targeted treatment approved for upfront use in adults with Ph+ ALL, Takeda said in a press release.
Ponatinib was previously approved as monotherapy for Ph+ ALL when no other kinase inhibitors are indicated or for T315I-positive Ph+ ALL, as well as for chronic myeloid leukemia.
Approval for the new indication was based on the PhALLCON trial. In the trial, 245 patients were randomized 2:1 to either ponatinib 30 mg once daily or the first-generation TKI imatinib (Gleevec, Novartis) 600 mg once daily on a chemotherapy background consisting of three cycles of vincristine/dexamethasone induction, six cycles methotrexate/cytarabine consolidation, and 11 cycles of vincristine/prednisone maintenance.
At the end of induction, 12% of patients in the imatinib arm vs 30% in the ponatinib group were in complete remission with no minimal residual disease. Event-free survival data are not yet mature.
At the 2023 American Society of Clinical Oncology annual meeting, an investigator on the trial said that ponatinib plus low-intensity chemotherapy has the potential to become the new standard of care for upfront Ph+ All. However, continued approval for the new indication may depend on trials confirming clinical benefit, Takeda said.
Ponatinib carries a boxed warning of arterial occlusive events, venous thromboembolic events, heart failure, and hepatotoxicity.
The most common adverse reactions reported in the PhALLCON trial were hepatic dysfunction, arthralgia, rash, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/elevated lipase, peripheral neuropathy, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias.
The recommended ponatinib dose is 30 mg orally once daily until the end of induction, dropping down to 15 mg once daily in patients who go into remission with no minimal residual disease after induction, for up to 20 cycles or until loss of response or unacceptable toxicity.
Thirty tablets of 30 mg or 15 mg cost $21,944.54, according to Drugs.com.
A version of this article appeared on Medscape.com.
The approval makes the third-generation tyrosine kinase inhibitor (TKI) the first targeted treatment approved for upfront use in adults with Ph+ ALL, Takeda said in a press release.
Ponatinib was previously approved as monotherapy for Ph+ ALL when no other kinase inhibitors are indicated or for T315I-positive Ph+ ALL, as well as for chronic myeloid leukemia.
Approval for the new indication was based on the PhALLCON trial. In the trial, 245 patients were randomized 2:1 to either ponatinib 30 mg once daily or the first-generation TKI imatinib (Gleevec, Novartis) 600 mg once daily on a chemotherapy background consisting of three cycles of vincristine/dexamethasone induction, six cycles methotrexate/cytarabine consolidation, and 11 cycles of vincristine/prednisone maintenance.
At the end of induction, 12% of patients in the imatinib arm vs 30% in the ponatinib group were in complete remission with no minimal residual disease. Event-free survival data are not yet mature.
At the 2023 American Society of Clinical Oncology annual meeting, an investigator on the trial said that ponatinib plus low-intensity chemotherapy has the potential to become the new standard of care for upfront Ph+ All. However, continued approval for the new indication may depend on trials confirming clinical benefit, Takeda said.
Ponatinib carries a boxed warning of arterial occlusive events, venous thromboembolic events, heart failure, and hepatotoxicity.
The most common adverse reactions reported in the PhALLCON trial were hepatic dysfunction, arthralgia, rash, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/elevated lipase, peripheral neuropathy, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias.
The recommended ponatinib dose is 30 mg orally once daily until the end of induction, dropping down to 15 mg once daily in patients who go into remission with no minimal residual disease after induction, for up to 20 cycles or until loss of response or unacceptable toxicity.
Thirty tablets of 30 mg or 15 mg cost $21,944.54, according to Drugs.com.
A version of this article appeared on Medscape.com.
New Drug Approvals Are the Wrong Metric for Cancer Policy
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
How should we define success in cancer policy — what should the endpoint be?
It’s debatable. Is it fewer cancer deaths? Perhaps improved access to therapies or a reduction in disparities?
One thing I know with certainty: The number of new cancer drugs approved by the US Food and Drug Administration (FDA) is not and should not be our primary endpoint in and of itself.
I’ll go a step further: It is not even a surrogate marker for success.
Unfortunately, a new drug approval does not necessarily mean improved patient outcomes. In fact, the majority of cancer drugs approved these days improve neither survival nor quality of life. Our previous work has shown better mortality outcomes in other high-income countries that have not approved or do not fund several cancer drugs that the FDA has approved.
Even if a drug has a meaningful benefit, at an average cost of more than $250,000 per year, if a new drug cannot reach patients because of access or cost issues, it’s meaningless.
However, regulators and media celebrate the number (and speed) of drug approvals every year as if it were a marker of success in and of itself. But approving more drugs should not be the goal; improving outcomes should. The FDA’s current approach is akin to a university celebrating its graduation rate by lowering the requirements to pass.
When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine ‘ending cancer as we know it’ is premature and even embarrassing.
This is exactly what the FDA has been doing with our regulatory standards for drug approval. They have gradually lowered the requirements for approval from two randomized trials to one randomized trial, then further to one randomized trial with a surrogate endpoint. In many instances, they have gone even further, demanding merely single-arm trials. They’ve also gone from requiring overall survival benefits to celebrating nondetrimental effects on overall survival. It’s no wonder that we approve more drugs today than we did in the past — the bar for approval is pretty low nowadays.
In 2019, our lab found an interesting phenomenon: The number of approvals based on surrogate endpoints has been increasing while the number of accelerated approvals has been decreasing. This made no sense at first, because you’d think surrogate-based approvals and accelerated approvals would be collinear. However, we realized that the recent approvals based on surrogate endpoints were regular approvals instead of accelerated approvals, which explained the phenomenon. Not only is the FDA approving more drugs on the basis of lower levels of evidence, but the agency is also offering regular instead of accelerated approval, thereby removing the safety net of a confirmatory trial.
Nearly everybody sees this as a cause for celebration. Pharma celebrates record profits, regulators celebrate record numbers of drug approvals, insurance companies celebrate because they can pass these costs on as insurance premiums and make even more money, and physicians and patients celebrate access to the shiniest, sexiest new cancer drug.
Everybody is happy in this system. The only problem is that patient outcomes don’t improve, resources are taken away from other priorities, and society suffers a net harm.
When you contrast this celebration with the reality on the ground, the difference is stark and sobering. In our clinics, patients lack access to even old chemotherapeutic drugs that are already generic and cheap but make a meaningful difference in patient outcomes. Citing a current lack of incentives, several generic cancer drug manufacturers have stopped making these drugs; the US supply now relies heavily on importing them from emerging economies such as India. When US patients lack access to cisplatin and carboplatin, any talk of a Moonshot or precision medicine “ending cancer as we know it” is premature and even embarrassing.
5-Fluorouracil, methotrexate, and the platinums are backbones of cancer treatment. Cisplatin and carboplatin are not drugs we use with the hope of improving survival by a couple of months; these drugs are the difference between life and death for patients with testicular and ovarian cancers. In a survey of 948 global oncologists, these were considered among the most essential cancer drugs by oncologists in high-income and low- and middle-income countries alike. Although oncologists in low- and middle-income countries sometimes argue that even these cheap generic drugs may be unaffordable to their patients, they usually remain available; access is a function of both availability and affordability. However, the shortage situation in the US is unique in that availability — rather than affordability — is impacting access.
Our profit-over-patients policy has landed us in a terrible paradox.
Generic drugs are cheap, and any industrialized country can manufacture them. This is why so few companies actually do so; the profit margins are low and companies have little incentive to produce them, despite their benefit. Meanwhile, the FDA is approving and offering access to new shiny molecules that cost more than $15,000 per month yet offer less than a month of progression-free survival benefit and no overall survival benefit (see margetuximab in breast cancer). We have a literal fatal attraction to everything new and shiny.
This is a clear misalignment of priorities in US cancer drug policy. Our profit-over-patients policy has landed us in a terrible paradox: If a drug is cheap and meaningful, it won’t be available, but if it is marginal and expensive, we will do everything to ensure patients can get it. It’s no wonder that patients on Medicaid are disproportionately affected by these drug shortages. Unless all patients have easy access to cisplatin, carboplatin, and 5-fluorouracil, it is frankly embarrassing to celebrate the number of new cancer drugs approved each year.
We all have a responsibility in this — policymakers and lawmakers, regulators and payers, manufacturers and distributors, the American Society of Clinical Oncology and other oncology societies, and physicians and patients. This is where our advocacy work should focus. The primary endpoint of our cancer policy should not be how many new treatments we can approve or how many expensive drugs a rich person with the best insurance can get at a leading cancer center. The true measure of our civilization is how it treats its most vulnerable members.
Dr. Gyawali has disclosed the following relevant financial relationship: Received consulting fees from Vivio Health.
Dr. Gyawali is an associate professor in the Departments of Oncology and Public Health Sciences and a scientist in the Division of Cancer Care and Epidemiology at Queen’s University in Kingston, Ontario, Canada, and is also affiliated faculty at the Program on Regulation, Therapeutics, and Law in the Department of Medicine at Brigham and Women’s Hospital in Boston. His clinical and research interests revolve around cancer policy, global oncology, evidence-based oncology, financial toxicities of cancer treatment, clinical trial methods, and supportive care. He tweets at @oncology_bg.
A version of this article appeared on Medscape.com.
Extraordinary Patients Inspired Father of Cancer Immunotherapy
His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.
To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.
Dr. Rosenberg, a senior investigator for the Center for Cancer Research at the National Cancer Institute (NCI), and chief of the NCI Surgery Branch, shared the history behind his novel research and the patient stories that inspired his discoveries, during an interview.
Tell us a little about yourself and where you grew up.
Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.
As a young boy, did you always want to become a doctor?
Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.
How did that experience impact your aspirations?
Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.
What led to your interest in cancer treatment?
Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.
Were there patients who inspired your research?
Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
Was the second patient’s case as impressive?
Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.
From there, how did your work evolve?
Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.
Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?
Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.
How did this finding impact your future discoveries?
Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.
What guidance would you have for other physician-investigators or young doctors who want to follow in your path?
Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.
His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.
To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.
Dr. Rosenberg, a senior investigator for the Center for Cancer Research at the National Cancer Institute (NCI), and chief of the NCI Surgery Branch, shared the history behind his novel research and the patient stories that inspired his discoveries, during an interview.
Tell us a little about yourself and where you grew up.
Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.
As a young boy, did you always want to become a doctor?
Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.
How did that experience impact your aspirations?
Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.
What led to your interest in cancer treatment?
Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.
Were there patients who inspired your research?
Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
Was the second patient’s case as impressive?
Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.
From there, how did your work evolve?
Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.
Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?
Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.
How did this finding impact your future discoveries?
Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.
What guidance would you have for other physician-investigators or young doctors who want to follow in your path?
Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.
His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.
To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.
Dr. Rosenberg, a senior investigator for the Center for Cancer Research at the National Cancer Institute (NCI), and chief of the NCI Surgery Branch, shared the history behind his novel research and the patient stories that inspired his discoveries, during an interview.
Tell us a little about yourself and where you grew up.
Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.
As a young boy, did you always want to become a doctor?
Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.
How did that experience impact your aspirations?
Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.
What led to your interest in cancer treatment?
Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.
Were there patients who inspired your research?
Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
Was the second patient’s case as impressive?
Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.
From there, how did your work evolve?
Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.
Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?
Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.
How did this finding impact your future discoveries?
Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.
What guidance would you have for other physician-investigators or young doctors who want to follow in your path?
Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.
Consider These Factors in an Academic Radiation Oncology Position
TOPLINE:
— and accept an offer if the practice is “great” in at least two of those areas and “good” in the third, experts say in a recent editorial.
METHODOLOGY:
- Many physicians choose to go into academic medicine because they want to stay involved in research and education while still treating patients.
- However, graduating radiation oncology residents often lack or have limited guidance on what to look for in a prospective job and how to assess their contract.
- This recent editorial provides guidance to radiation oncologists seeking academic positions. The authors advise prospective employees to evaluate three main factors — compensation, daily duties, and location — as well as provide tips for identifying red flags in each category.
TAKEAWAY:
- Compensation: Prospective faculty should assess both direct compensation, that is, salary, and indirect compensation, which typically includes retirement contributions and other perks. For direct compensation, what is the base salary? Is extra work compensated? How does the salary offer measure up to salary data reported by national agencies? Also: Don’t overlook uncompensated duties, such as time in tumor boards or in meetings, which may be time-consuming, and make sure compensation terms are clearly delineated in a contract and equitable among physicians in a specific rank.
- Daily duties: When it comes to daily life on the job, a prospective employee should consider many factors, including the cancer center’s excitement to hire you, the reputation of the faculty and leaders at the organization, employee turnover rates, diversity among faculty, and the time line of career advancement.
- Location: The location of the job encompasses the geography — such as distance from home to work, the number of practices covered, cost of living, and the area itself — as well as the atmosphere for conducting research and publishing.
- Finally, carefully review the job contract. All the key aspects of the job, including compensation and benefits, should be clearly stated in the contract to “improve communication of expectations.”
IN PRACTICE:
“A prospective faculty member can ask 100 questions, but they can’t make 100 demands; consideration of the three domains can help to focus negotiation efforts where the efforts are needed,” the authors noted.
SOURCE:
This editorial, led by Nicholas G. Zaorsky from the Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve School of Medicine, Cleveland, Ohio, was published online in Practical Radiation Oncology
DISCLOSURES:
The lead author declared being supported by the American Cancer Society and National Institutes of Health. He also reported having ties with many other sources.
A version of this article appeared on Medscape.com.
TOPLINE:
— and accept an offer if the practice is “great” in at least two of those areas and “good” in the third, experts say in a recent editorial.
METHODOLOGY:
- Many physicians choose to go into academic medicine because they want to stay involved in research and education while still treating patients.
- However, graduating radiation oncology residents often lack or have limited guidance on what to look for in a prospective job and how to assess their contract.
- This recent editorial provides guidance to radiation oncologists seeking academic positions. The authors advise prospective employees to evaluate three main factors — compensation, daily duties, and location — as well as provide tips for identifying red flags in each category.
TAKEAWAY:
- Compensation: Prospective faculty should assess both direct compensation, that is, salary, and indirect compensation, which typically includes retirement contributions and other perks. For direct compensation, what is the base salary? Is extra work compensated? How does the salary offer measure up to salary data reported by national agencies? Also: Don’t overlook uncompensated duties, such as time in tumor boards or in meetings, which may be time-consuming, and make sure compensation terms are clearly delineated in a contract and equitable among physicians in a specific rank.
- Daily duties: When it comes to daily life on the job, a prospective employee should consider many factors, including the cancer center’s excitement to hire you, the reputation of the faculty and leaders at the organization, employee turnover rates, diversity among faculty, and the time line of career advancement.
- Location: The location of the job encompasses the geography — such as distance from home to work, the number of practices covered, cost of living, and the area itself — as well as the atmosphere for conducting research and publishing.
- Finally, carefully review the job contract. All the key aspects of the job, including compensation and benefits, should be clearly stated in the contract to “improve communication of expectations.”
IN PRACTICE:
“A prospective faculty member can ask 100 questions, but they can’t make 100 demands; consideration of the three domains can help to focus negotiation efforts where the efforts are needed,” the authors noted.
SOURCE:
This editorial, led by Nicholas G. Zaorsky from the Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve School of Medicine, Cleveland, Ohio, was published online in Practical Radiation Oncology
DISCLOSURES:
The lead author declared being supported by the American Cancer Society and National Institutes of Health. He also reported having ties with many other sources.
A version of this article appeared on Medscape.com.
TOPLINE:
— and accept an offer if the practice is “great” in at least two of those areas and “good” in the third, experts say in a recent editorial.
METHODOLOGY:
- Many physicians choose to go into academic medicine because they want to stay involved in research and education while still treating patients.
- However, graduating radiation oncology residents often lack or have limited guidance on what to look for in a prospective job and how to assess their contract.
- This recent editorial provides guidance to radiation oncologists seeking academic positions. The authors advise prospective employees to evaluate three main factors — compensation, daily duties, and location — as well as provide tips for identifying red flags in each category.
TAKEAWAY:
- Compensation: Prospective faculty should assess both direct compensation, that is, salary, and indirect compensation, which typically includes retirement contributions and other perks. For direct compensation, what is the base salary? Is extra work compensated? How does the salary offer measure up to salary data reported by national agencies? Also: Don’t overlook uncompensated duties, such as time in tumor boards or in meetings, which may be time-consuming, and make sure compensation terms are clearly delineated in a contract and equitable among physicians in a specific rank.
- Daily duties: When it comes to daily life on the job, a prospective employee should consider many factors, including the cancer center’s excitement to hire you, the reputation of the faculty and leaders at the organization, employee turnover rates, diversity among faculty, and the time line of career advancement.
- Location: The location of the job encompasses the geography — such as distance from home to work, the number of practices covered, cost of living, and the area itself — as well as the atmosphere for conducting research and publishing.
- Finally, carefully review the job contract. All the key aspects of the job, including compensation and benefits, should be clearly stated in the contract to “improve communication of expectations.”
IN PRACTICE:
“A prospective faculty member can ask 100 questions, but they can’t make 100 demands; consideration of the three domains can help to focus negotiation efforts where the efforts are needed,” the authors noted.
SOURCE:
This editorial, led by Nicholas G. Zaorsky from the Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve School of Medicine, Cleveland, Ohio, was published online in Practical Radiation Oncology
DISCLOSURES:
The lead author declared being supported by the American Cancer Society and National Institutes of Health. He also reported having ties with many other sources.
A version of this article appeared on Medscape.com.
Look Beyond BMI: Metabolic Factors’ Link to Cancer Explained
The new research finds that adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer.
The conditions that make up metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, and colleagues.
However, a single assessment of metabolic syndrome at one point in time is inadequate to show an association with cancer risk over time, they said. In the current study, the researchers used models to examine the association between trajectory patterns of metabolic syndrome over time and the risk of overall and specific cancer types. They also examined the impact of chronic inflammation concurrent with metabolic syndrome.
What We Know About Metabolic Syndrome and Cancer Risk
A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.
More recently, a 2020 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.
In addition, a 2022 study by some of the current study researchers of the same Chinese cohort focused on the role of inflammation in combination with metabolic syndrome on colorectal cancer specifically, and found an increased risk for cancer when both metabolic syndrome and inflammation were present.
However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.
“There is emerging evidence that even normal weight individuals who are metabolically unhealthy may be at an elevated cancer risk, and we need better metrics to define the underlying metabolic dysfunction in obesity,” Sheetal Hardikar, MBBS, PhD, MPH, an investigator at the Huntsman Cancer Institute, University of Utah, said in an interview.
Dr. Hardikar, who serves as assistant professor in the department of population health sciences at the University of Utah, was not involved in the current study. She and her colleagues published a research paper on data from the National Health and Nutrition Examination Survey in 2023 that showed an increased risk of obesity-related cancer.
What New Study Adds to Related Research
Previous studies have consistently reported an approximately 30% increased risk of cancer with metabolic syndrome, Dr. Hardikar said. “What is unique about this study is the examination of metabolic syndrome trajectories over four years, and not just the presence of metabolic syndrome at one point in time,” she said.
In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).
The average age of the participants was 49 years; the mean body mass index ranged from approximately 22 kg/m2 in the low-stable group to approximately 28 kg/m2 in the elevated-increasing group.
The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.
Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.
The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
What Are the Limitations of This Research?
The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.
Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.
Using the International Diabetes Federation criteria was another limitation, because it prevented the assessment of cancer risk in normal weight individuals with metabolic dysfunction, Dr. Hardikar noted.
Does Metabolic Syndrome Cause Cancer?
“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, noted in a statement on the study.
More research is needed to assess the impact of these interventions on cancer risk. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he continued.
“Current evidence based on this study and many other reports strongly suggests an increased risk for cancer associated with metabolic syndrome,” Dr. Hardikar said in an interview. The data serve as a reminder to clinicians to look beyond BMI as the only measure of obesity, and to consider metabolic factors together to identify individuals at increased risk for cancer, she said.
“We must continue to educate patients about obesity and all the chronic conditions it may lead to, but we cannot ignore this emerging phenotype of being of normal weight but metabolically unhealthy,” Dr. Hardikar emphasized.
What Additional Research is Needed?
Looking ahead, “we need well-designed interventions to test causality for metabolic syndrome and cancer risk, though the evidence from the observational studies is very strong,” Dr. Hardikar said.
In addition, a consensus is needed to better define metabolic dysfunction,and to explore cancer risk in normal weight but metabolically unhealthy individuals, she said.
The study was supported by the National Key Research and Development Program of China. The researchers and Dr. Hardikar had no financial conflicts to disclose.
The new research finds that adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer.
The conditions that make up metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, and colleagues.
However, a single assessment of metabolic syndrome at one point in time is inadequate to show an association with cancer risk over time, they said. In the current study, the researchers used models to examine the association between trajectory patterns of metabolic syndrome over time and the risk of overall and specific cancer types. They also examined the impact of chronic inflammation concurrent with metabolic syndrome.
What We Know About Metabolic Syndrome and Cancer Risk
A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.
More recently, a 2020 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.
In addition, a 2022 study by some of the current study researchers of the same Chinese cohort focused on the role of inflammation in combination with metabolic syndrome on colorectal cancer specifically, and found an increased risk for cancer when both metabolic syndrome and inflammation were present.
However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.
“There is emerging evidence that even normal weight individuals who are metabolically unhealthy may be at an elevated cancer risk, and we need better metrics to define the underlying metabolic dysfunction in obesity,” Sheetal Hardikar, MBBS, PhD, MPH, an investigator at the Huntsman Cancer Institute, University of Utah, said in an interview.
Dr. Hardikar, who serves as assistant professor in the department of population health sciences at the University of Utah, was not involved in the current study. She and her colleagues published a research paper on data from the National Health and Nutrition Examination Survey in 2023 that showed an increased risk of obesity-related cancer.
What New Study Adds to Related Research
Previous studies have consistently reported an approximately 30% increased risk of cancer with metabolic syndrome, Dr. Hardikar said. “What is unique about this study is the examination of metabolic syndrome trajectories over four years, and not just the presence of metabolic syndrome at one point in time,” she said.
In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).
The average age of the participants was 49 years; the mean body mass index ranged from approximately 22 kg/m2 in the low-stable group to approximately 28 kg/m2 in the elevated-increasing group.
The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.
Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.
The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
What Are the Limitations of This Research?
The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.
Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.
Using the International Diabetes Federation criteria was another limitation, because it prevented the assessment of cancer risk in normal weight individuals with metabolic dysfunction, Dr. Hardikar noted.
Does Metabolic Syndrome Cause Cancer?
“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, noted in a statement on the study.
More research is needed to assess the impact of these interventions on cancer risk. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he continued.
“Current evidence based on this study and many other reports strongly suggests an increased risk for cancer associated with metabolic syndrome,” Dr. Hardikar said in an interview. The data serve as a reminder to clinicians to look beyond BMI as the only measure of obesity, and to consider metabolic factors together to identify individuals at increased risk for cancer, she said.
“We must continue to educate patients about obesity and all the chronic conditions it may lead to, but we cannot ignore this emerging phenotype of being of normal weight but metabolically unhealthy,” Dr. Hardikar emphasized.
What Additional Research is Needed?
Looking ahead, “we need well-designed interventions to test causality for metabolic syndrome and cancer risk, though the evidence from the observational studies is very strong,” Dr. Hardikar said.
In addition, a consensus is needed to better define metabolic dysfunction,and to explore cancer risk in normal weight but metabolically unhealthy individuals, she said.
The study was supported by the National Key Research and Development Program of China. The researchers and Dr. Hardikar had no financial conflicts to disclose.
The new research finds that adults with persistent metabolic syndrome that worsens over time are at increased risk for any type of cancer.
The conditions that make up metabolic syndrome (high blood pressure, high blood sugar, increased abdominal adiposity, and high cholesterol and triglycerides) have been associated with an increased risk of diseases, including heart disease, stroke, and type 2 diabetes, wrote Li Deng, PhD, of Capital Medical University, Beijing, and colleagues.
However, a single assessment of metabolic syndrome at one point in time is inadequate to show an association with cancer risk over time, they said. In the current study, the researchers used models to examine the association between trajectory patterns of metabolic syndrome over time and the risk of overall and specific cancer types. They also examined the impact of chronic inflammation concurrent with metabolic syndrome.
What We Know About Metabolic Syndrome and Cancer Risk
A systematic review and meta-analysis published in Diabetes Care in 2012 showed an association between the presence of metabolic syndrome and an increased risk of various cancers including liver, bladder, pancreatic, breast, and colorectal.
More recently, a 2020 study published in Diabetes showed evidence of increased risk for certain cancers (pancreatic, kidney, uterine, cervical) but no increased risk for cancer overall.
In addition, a 2022 study by some of the current study researchers of the same Chinese cohort focused on the role of inflammation in combination with metabolic syndrome on colorectal cancer specifically, and found an increased risk for cancer when both metabolic syndrome and inflammation were present.
However, the reasons for this association between metabolic syndrome and cancer remain unclear, and the effect of the fluctuating nature of metabolic syndrome over time on long-term cancer risk has not been explored, the researchers wrote.
“There is emerging evidence that even normal weight individuals who are metabolically unhealthy may be at an elevated cancer risk, and we need better metrics to define the underlying metabolic dysfunction in obesity,” Sheetal Hardikar, MBBS, PhD, MPH, an investigator at the Huntsman Cancer Institute, University of Utah, said in an interview.
Dr. Hardikar, who serves as assistant professor in the department of population health sciences at the University of Utah, was not involved in the current study. She and her colleagues published a research paper on data from the National Health and Nutrition Examination Survey in 2023 that showed an increased risk of obesity-related cancer.
What New Study Adds to Related Research
Previous studies have consistently reported an approximately 30% increased risk of cancer with metabolic syndrome, Dr. Hardikar said. “What is unique about this study is the examination of metabolic syndrome trajectories over four years, and not just the presence of metabolic syndrome at one point in time,” she said.
In the new study, published in Cancer on March 11 (doi: 10.1002/cncr.35235), 44,115 adults in China were separated into four trajectories based on metabolic syndrome scores for the period from 2006 to 2010. The scores were based on clinical evidence of metabolic syndrome, defined using the International Diabetes Federation criteria of central obesity and the presence of at least two other factors including increased triglycerides, decreased HDL cholesterol, high blood pressure (or treatment for previously diagnosed hypertension), and increased fasting plasma glucose (or previous diagnosis of type 2 diabetes).
The average age of the participants was 49 years; the mean body mass index ranged from approximately 22 kg/m2 in the low-stable group to approximately 28 kg/m2 in the elevated-increasing group.
The four trajectories of metabolic syndrome were low-stable (10.56% of participants), moderate-low (40.84%), moderate-high (41.46%), and elevated-increasing (7.14%), based on trends from the individuals’ initial physical exams on entering the study.
Over a median follow-up period of 9.4 years (from 2010 to 2021), 2,271 cancer diagnoses were reported in the study population. Those with an elevated-increasing metabolic syndrome trajectory had 1.3 times the risk of any cancer compared with those in the low-stable group. Risk for breast cancer, endometrial cancer, kidney cancer, colorectal cancer, and liver cancer in the highest trajectory group were 2.1, 3.3, 4.5, 2.5, and 1.6 times higher, respectively, compared to the lowest group. The increased risk in the elevated-trajectory group for all cancer types persisted when the low-stable, moderate-low, and moderate-high trajectory pattern groups were combined.
The researchers also examined the impact of chronic inflammation and found that individuals with persistently high metabolic syndrome scores and concurrent chronic inflammation had the highest risks of breast, endometrial, colon, and liver cancer. However, individuals with persistently high metabolic syndrome scores and no concurrent chronic inflammation had the highest risk of kidney cancer.
What Are the Limitations of This Research?
The researchers of the current study acknowledged the lack of information on other causes of cancer, including dietary habits, hepatitis C infection, and Helicobacter pylori infection. Other limitations include the focus only on individuals from a single community of mainly middle-aged men in China that may not generalize to other populations.
Also, the metabolic syndrome trajectories did not change much over time, which may be related to the short 4-year study period.
Using the International Diabetes Federation criteria was another limitation, because it prevented the assessment of cancer risk in normal weight individuals with metabolic dysfunction, Dr. Hardikar noted.
Does Metabolic Syndrome Cause Cancer?
“This research suggests that proactive and continuous management of metabolic syndrome may serve as an essential strategy in preventing cancer,” senior author Han-Ping Shi, MD, PhD, of Capital Medical University in Beijing, noted in a statement on the study.
More research is needed to assess the impact of these interventions on cancer risk. However, the data from the current study can guide future research that may lead to more targeted treatments and more effective preventive strategies, he continued.
“Current evidence based on this study and many other reports strongly suggests an increased risk for cancer associated with metabolic syndrome,” Dr. Hardikar said in an interview. The data serve as a reminder to clinicians to look beyond BMI as the only measure of obesity, and to consider metabolic factors together to identify individuals at increased risk for cancer, she said.
“We must continue to educate patients about obesity and all the chronic conditions it may lead to, but we cannot ignore this emerging phenotype of being of normal weight but metabolically unhealthy,” Dr. Hardikar emphasized.
What Additional Research is Needed?
Looking ahead, “we need well-designed interventions to test causality for metabolic syndrome and cancer risk, though the evidence from the observational studies is very strong,” Dr. Hardikar said.
In addition, a consensus is needed to better define metabolic dysfunction,and to explore cancer risk in normal weight but metabolically unhealthy individuals, she said.
The study was supported by the National Key Research and Development Program of China. The researchers and Dr. Hardikar had no financial conflicts to disclose.
FROM CANCER