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Depression and anxiety were not associated with outcomes for most cancer types, including breast cancer, prostate cancer, and alcohol-related cancer, according to findings from a large, individual participant data meta-analysis.

An exception was for lung and smoking-related cancers, but key covariates appeared to explain the relationship between depression, anxiety, and these cancer types, the investigators reported.

The findings challenge a common theory that depression and anxiety increase cancer risk and should “change current thinking,” they argue.

“Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” first author Lonneke A. van Tuijl, PhD, of the University of Groningen and Utrecht University, the Netherlands, noted in a press release.

Analyses included data from up to nearly 320,000 individuals from the 18 prospective cohorts included in the international Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. The cohorts are from studies conducted in the Netherlands, United Kingdom, Norway, and Canada, and included 25,803 patients with cancer. During follow-up of up to 26 years and more than 3.2 million person-years, depression and anxiety symptoms and diagnoses showed no association with overall breast, prostate, colorectal, and alcohol-related cancers (hazard ratios, 0.98-1.05).

For the specific cancer types, the investigators “found no evidence for an association between depression or anxiety and the incidence of colorectal cancer (HRs, 0.88-1.13), prostate cancer (HRs, 0.97-1.17), or alcohol-related cancers (HRs, 0.97-1.06).”

“For breast cancer, all pooled HRs were consistently negative but mean pooled HRs were close to 1 (HRs, 0.92-0.98) and the upper limit of the 95% confidence intervals all exceeded 1 (with the exception of anxiety symptoms),” they noted.

An increase in risk observed between depression and anxiety symptoms and diagnoses and lung cancer (HRs, 1.12-1.60) and smoking-related cancers (HRs, 1.06-1.60), in minimally adjusted models, was substantially attenuated after adjusting for known risk factors such as smoking, alcohol use, and body mass index (HRs, 1.04-1.08), the investigators reported.

The findings were published online in Cancer.

“Depression and anxiety have long been hypothesized to increase the risk for cancer. It is thought that the increased cancer risk can occur via several pathways, including health behaviors, or by influencing mutation, viral oncogenes, cell proliferation, or DNA repair,” the authors explained, noting that “[c]onclusions drawn in meta-analyses vary greatly, with some supporting an association between depression, anxiety, and cancer incidence and others finding no or a negligible association.”

The current findings “may help health professionals to alleviate feelings of guilt and self-blame in patients with cancer who attribute their diagnosis to previous depression or anxiety,” they said, noting that the findings “also underscore the importance of addressing tobacco smoking and other unhealthy behaviors – including those that may develop as a result of anxiety or depression.”

“However, further research is needed to understand exactly how depression, anxiety, health behaviors, and lung cancer are related,” said Dr. Tuijl.

Dr. Tuijl has received grants and travel support from the Dutch Cancer Society (KWF).
 

Depression and anxiety were not associated with outcomes for most cancer types, including breast cancer, prostate cancer, and alcohol-related cancer, according to findings from a large, individual participant data meta-analysis.

An exception was for lung and smoking-related cancers, but key covariates appeared to explain the relationship between depression, anxiety, and these cancer types, the investigators reported.

The findings challenge a common theory that depression and anxiety increase cancer risk and should “change current thinking,” they argue.

“Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” first author Lonneke A. van Tuijl, PhD, of the University of Groningen and Utrecht University, the Netherlands, noted in a press release.

Analyses included data from up to nearly 320,000 individuals from the 18 prospective cohorts included in the international Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. The cohorts are from studies conducted in the Netherlands, United Kingdom, Norway, and Canada, and included 25,803 patients with cancer. During follow-up of up to 26 years and more than 3.2 million person-years, depression and anxiety symptoms and diagnoses showed no association with overall breast, prostate, colorectal, and alcohol-related cancers (hazard ratios, 0.98-1.05).

For the specific cancer types, the investigators “found no evidence for an association between depression or anxiety and the incidence of colorectal cancer (HRs, 0.88-1.13), prostate cancer (HRs, 0.97-1.17), or alcohol-related cancers (HRs, 0.97-1.06).”

“For breast cancer, all pooled HRs were consistently negative but mean pooled HRs were close to 1 (HRs, 0.92-0.98) and the upper limit of the 95% confidence intervals all exceeded 1 (with the exception of anxiety symptoms),” they noted.

An increase in risk observed between depression and anxiety symptoms and diagnoses and lung cancer (HRs, 1.12-1.60) and smoking-related cancers (HRs, 1.06-1.60), in minimally adjusted models, was substantially attenuated after adjusting for known risk factors such as smoking, alcohol use, and body mass index (HRs, 1.04-1.08), the investigators reported.

The findings were published online in Cancer.

“Depression and anxiety have long been hypothesized to increase the risk for cancer. It is thought that the increased cancer risk can occur via several pathways, including health behaviors, or by influencing mutation, viral oncogenes, cell proliferation, or DNA repair,” the authors explained, noting that “[c]onclusions drawn in meta-analyses vary greatly, with some supporting an association between depression, anxiety, and cancer incidence and others finding no or a negligible association.”

The current findings “may help health professionals to alleviate feelings of guilt and self-blame in patients with cancer who attribute their diagnosis to previous depression or anxiety,” they said, noting that the findings “also underscore the importance of addressing tobacco smoking and other unhealthy behaviors – including those that may develop as a result of anxiety or depression.”

“However, further research is needed to understand exactly how depression, anxiety, health behaviors, and lung cancer are related,” said Dr. Tuijl.

Dr. Tuijl has received grants and travel support from the Dutch Cancer Society (KWF).
 

Depression and anxiety were not associated with outcomes for most cancer types, including breast cancer, prostate cancer, and alcohol-related cancer, according to findings from a large, individual participant data meta-analysis.

An exception was for lung and smoking-related cancers, but key covariates appeared to explain the relationship between depression, anxiety, and these cancer types, the investigators reported.

The findings challenge a common theory that depression and anxiety increase cancer risk and should “change current thinking,” they argue.

“Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” first author Lonneke A. van Tuijl, PhD, of the University of Groningen and Utrecht University, the Netherlands, noted in a press release.

Analyses included data from up to nearly 320,000 individuals from the 18 prospective cohorts included in the international Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. The cohorts are from studies conducted in the Netherlands, United Kingdom, Norway, and Canada, and included 25,803 patients with cancer. During follow-up of up to 26 years and more than 3.2 million person-years, depression and anxiety symptoms and diagnoses showed no association with overall breast, prostate, colorectal, and alcohol-related cancers (hazard ratios, 0.98-1.05).

For the specific cancer types, the investigators “found no evidence for an association between depression or anxiety and the incidence of colorectal cancer (HRs, 0.88-1.13), prostate cancer (HRs, 0.97-1.17), or alcohol-related cancers (HRs, 0.97-1.06).”

“For breast cancer, all pooled HRs were consistently negative but mean pooled HRs were close to 1 (HRs, 0.92-0.98) and the upper limit of the 95% confidence intervals all exceeded 1 (with the exception of anxiety symptoms),” they noted.

An increase in risk observed between depression and anxiety symptoms and diagnoses and lung cancer (HRs, 1.12-1.60) and smoking-related cancers (HRs, 1.06-1.60), in minimally adjusted models, was substantially attenuated after adjusting for known risk factors such as smoking, alcohol use, and body mass index (HRs, 1.04-1.08), the investigators reported.

The findings were published online in Cancer.

“Depression and anxiety have long been hypothesized to increase the risk for cancer. It is thought that the increased cancer risk can occur via several pathways, including health behaviors, or by influencing mutation, viral oncogenes, cell proliferation, or DNA repair,” the authors explained, noting that “[c]onclusions drawn in meta-analyses vary greatly, with some supporting an association between depression, anxiety, and cancer incidence and others finding no or a negligible association.”

The current findings “may help health professionals to alleviate feelings of guilt and self-blame in patients with cancer who attribute their diagnosis to previous depression or anxiety,” they said, noting that the findings “also underscore the importance of addressing tobacco smoking and other unhealthy behaviors – including those that may develop as a result of anxiety or depression.”

“However, further research is needed to understand exactly how depression, anxiety, health behaviors, and lung cancer are related,” said Dr. Tuijl.

Dr. Tuijl has received grants and travel support from the Dutch Cancer Society (KWF).
 

Vitamin D supplementation significantly reduced the risk of relapse or death in a subgroup of patients with digestive tract cancer who were p53-immunoreactive, a recent analysis found.

In the p53-immunoreactive subgroup, daily vitamin D supplementation reduced the risk of relapse or death by 73%. Overall, the 5-year relapse-free survival (RFS) among those receiving vitamin D was 81% vs. almost 31% in the placebo group.

Vitamin D supplementation, however, had no effect on survival outcomes in the non–p53-immunoreactive subgroup.

©Kaspri/Fotolia.com

These findings represent a “game changer” for vitamin D and cancer, Michael Holick, PhD, MD, with Boston University, said in an editorial accompanying the study, published online in JAMA Network Open. The AMATERASU trial “provides an additional variable in our understanding of whether improving vitamin D status has any benefit for reducing risk of developing cancer as well as improving relapse-free and mortality outcomes.”

A growing body of research suggests that vitamin D supplementation may reduce the risk of cancer mortality, but the evidence remains mixed and efficacy may hinge on a patient’s tumor biology, specifically the p53 protein, the authors of the current analysis explained.

A 2019 randomized controlled trial from the research team found vitamin D supplements of 2000 IU/day did not improve RFS at 5 years in patients with digestive tract cancers. However, a post hoc analysis of the AMATERASU trial published in 2020 suggested that vitamin D supplementation improved RFS in a subgroup of patients with p53-positive digestive tract cancers, as seen using immunohistochemistry (IHC) staining (79% vs. 57% in the placebo group; hazard ratio, 0.52; P = .02).

In the current post hoc analysis of the AMATERASU trial, the research team explored whether vitamin D supplementation reduced the risk of relapse or death in the subgroup of patients who were p53 immunoreactive, defined as positivity for both nuclear accumulation of the p53 protein in more than 99% of cancer cells, as seen on IHC staining, as well as anti-p53 antibodies in serum.

In the trial, patients with stage I-III luminal gastrointestinal cancer who had undergone complete tumor resection were randomly assigned to receive placebo or oral vitamin D supplements of 2,000 IU/day from their first postoperative visit through the end of the trial, up to 8 years.

The current post hoc analysis by p53-immunoreactive status included 392 patients, of whom 47% had colorectal cancer, 43% had gastric cancer, 9% had esophageal cancer, and 0.5% had small-bowel cancer.

The post hoc analysis found that, among the p53-immunoreactive subgroup of 80 patients, relapse or death occurred in 9 of 54 patients (17%) in the vitamin D group and 14 of 26 patients (54%) in the placebo group. The 5-year RFS was significantly higher in the vitamin D group than the placebo group (81% vs. 31%; HR, 0.27; P = .002).

This was not the case in the 272 patients in the non–p53-immunoreactive subgroup. In this group, vitamin D supplementation had no apparent effect on 5-year RFS, compared with placebo (22% vs. 21%; HR, 1.09; 95% confidence interval, 0.65-1.84).

The main findings of this study were that daily supplementation of 2000 IU of vitamin D reduced the risk of relapse or death, compared with placebo, in the p53-immunoreactive subgroup, and they “suggest the importance of developing cancer immunotherapy targeting mutated p53 proteins,” study investigator Mitsuyoshi Urashima, MD, PhD, MPH, with Jikei University, Tokyo, and colleagues concluded.

Support for the study was provided by the Japan-Supported Program for the Strategic Research Foundation at Private Universities and a grant from the Japan Society for the Promotion of Science of the Ministry of Education, Culture, Sports, Science, and Technology. The authors report no relevant financial relationships. Dr. Holick reported grants from Carbogen Amcis and Solius; personal fees from Biogena, Sanofi, Faes Farma, Eric Anthony Nepute, and others; nonfinancial support from Ontometrics outside the submitted work; and had a patent for Novel Use of 25 hydroxy vitamin D pending for Carbogen Amcis BV and Aamanya AG.

A version of this article appeared on Medscape.com.

Vitamin D supplementation significantly reduced the risk of relapse or death in a subgroup of patients with digestive tract cancer who were p53-immunoreactive, a recent analysis found.

In the p53-immunoreactive subgroup, daily vitamin D supplementation reduced the risk of relapse or death by 73%. Overall, the 5-year relapse-free survival (RFS) among those receiving vitamin D was 81% vs. almost 31% in the placebo group.

Vitamin D supplementation, however, had no effect on survival outcomes in the non–p53-immunoreactive subgroup.

©Kaspri/Fotolia.com

These findings represent a “game changer” for vitamin D and cancer, Michael Holick, PhD, MD, with Boston University, said in an editorial accompanying the study, published online in JAMA Network Open. The AMATERASU trial “provides an additional variable in our understanding of whether improving vitamin D status has any benefit for reducing risk of developing cancer as well as improving relapse-free and mortality outcomes.”

A growing body of research suggests that vitamin D supplementation may reduce the risk of cancer mortality, but the evidence remains mixed and efficacy may hinge on a patient’s tumor biology, specifically the p53 protein, the authors of the current analysis explained.

A 2019 randomized controlled trial from the research team found vitamin D supplements of 2000 IU/day did not improve RFS at 5 years in patients with digestive tract cancers. However, a post hoc analysis of the AMATERASU trial published in 2020 suggested that vitamin D supplementation improved RFS in a subgroup of patients with p53-positive digestive tract cancers, as seen using immunohistochemistry (IHC) staining (79% vs. 57% in the placebo group; hazard ratio, 0.52; P = .02).

In the current post hoc analysis of the AMATERASU trial, the research team explored whether vitamin D supplementation reduced the risk of relapse or death in the subgroup of patients who were p53 immunoreactive, defined as positivity for both nuclear accumulation of the p53 protein in more than 99% of cancer cells, as seen on IHC staining, as well as anti-p53 antibodies in serum.

In the trial, patients with stage I-III luminal gastrointestinal cancer who had undergone complete tumor resection were randomly assigned to receive placebo or oral vitamin D supplements of 2,000 IU/day from their first postoperative visit through the end of the trial, up to 8 years.

The current post hoc analysis by p53-immunoreactive status included 392 patients, of whom 47% had colorectal cancer, 43% had gastric cancer, 9% had esophageal cancer, and 0.5% had small-bowel cancer.

The post hoc analysis found that, among the p53-immunoreactive subgroup of 80 patients, relapse or death occurred in 9 of 54 patients (17%) in the vitamin D group and 14 of 26 patients (54%) in the placebo group. The 5-year RFS was significantly higher in the vitamin D group than the placebo group (81% vs. 31%; HR, 0.27; P = .002).

This was not the case in the 272 patients in the non–p53-immunoreactive subgroup. In this group, vitamin D supplementation had no apparent effect on 5-year RFS, compared with placebo (22% vs. 21%; HR, 1.09; 95% confidence interval, 0.65-1.84).

The main findings of this study were that daily supplementation of 2000 IU of vitamin D reduced the risk of relapse or death, compared with placebo, in the p53-immunoreactive subgroup, and they “suggest the importance of developing cancer immunotherapy targeting mutated p53 proteins,” study investigator Mitsuyoshi Urashima, MD, PhD, MPH, with Jikei University, Tokyo, and colleagues concluded.

Support for the study was provided by the Japan-Supported Program for the Strategic Research Foundation at Private Universities and a grant from the Japan Society for the Promotion of Science of the Ministry of Education, Culture, Sports, Science, and Technology. The authors report no relevant financial relationships. Dr. Holick reported grants from Carbogen Amcis and Solius; personal fees from Biogena, Sanofi, Faes Farma, Eric Anthony Nepute, and others; nonfinancial support from Ontometrics outside the submitted work; and had a patent for Novel Use of 25 hydroxy vitamin D pending for Carbogen Amcis BV and Aamanya AG.

A version of this article appeared on Medscape.com.

Vitamin D supplementation significantly reduced the risk of relapse or death in a subgroup of patients with digestive tract cancer who were p53-immunoreactive, a recent analysis found.

In the p53-immunoreactive subgroup, daily vitamin D supplementation reduced the risk of relapse or death by 73%. Overall, the 5-year relapse-free survival (RFS) among those receiving vitamin D was 81% vs. almost 31% in the placebo group.

Vitamin D supplementation, however, had no effect on survival outcomes in the non–p53-immunoreactive subgroup.

©Kaspri/Fotolia.com

These findings represent a “game changer” for vitamin D and cancer, Michael Holick, PhD, MD, with Boston University, said in an editorial accompanying the study, published online in JAMA Network Open. The AMATERASU trial “provides an additional variable in our understanding of whether improving vitamin D status has any benefit for reducing risk of developing cancer as well as improving relapse-free and mortality outcomes.”

A growing body of research suggests that vitamin D supplementation may reduce the risk of cancer mortality, but the evidence remains mixed and efficacy may hinge on a patient’s tumor biology, specifically the p53 protein, the authors of the current analysis explained.

A 2019 randomized controlled trial from the research team found vitamin D supplements of 2000 IU/day did not improve RFS at 5 years in patients with digestive tract cancers. However, a post hoc analysis of the AMATERASU trial published in 2020 suggested that vitamin D supplementation improved RFS in a subgroup of patients with p53-positive digestive tract cancers, as seen using immunohistochemistry (IHC) staining (79% vs. 57% in the placebo group; hazard ratio, 0.52; P = .02).

In the current post hoc analysis of the AMATERASU trial, the research team explored whether vitamin D supplementation reduced the risk of relapse or death in the subgroup of patients who were p53 immunoreactive, defined as positivity for both nuclear accumulation of the p53 protein in more than 99% of cancer cells, as seen on IHC staining, as well as anti-p53 antibodies in serum.

In the trial, patients with stage I-III luminal gastrointestinal cancer who had undergone complete tumor resection were randomly assigned to receive placebo or oral vitamin D supplements of 2,000 IU/day from their first postoperative visit through the end of the trial, up to 8 years.

The current post hoc analysis by p53-immunoreactive status included 392 patients, of whom 47% had colorectal cancer, 43% had gastric cancer, 9% had esophageal cancer, and 0.5% had small-bowel cancer.

The post hoc analysis found that, among the p53-immunoreactive subgroup of 80 patients, relapse or death occurred in 9 of 54 patients (17%) in the vitamin D group and 14 of 26 patients (54%) in the placebo group. The 5-year RFS was significantly higher in the vitamin D group than the placebo group (81% vs. 31%; HR, 0.27; P = .002).

This was not the case in the 272 patients in the non–p53-immunoreactive subgroup. In this group, vitamin D supplementation had no apparent effect on 5-year RFS, compared with placebo (22% vs. 21%; HR, 1.09; 95% confidence interval, 0.65-1.84).

The main findings of this study were that daily supplementation of 2000 IU of vitamin D reduced the risk of relapse or death, compared with placebo, in the p53-immunoreactive subgroup, and they “suggest the importance of developing cancer immunotherapy targeting mutated p53 proteins,” study investigator Mitsuyoshi Urashima, MD, PhD, MPH, with Jikei University, Tokyo, and colleagues concluded.

Support for the study was provided by the Japan-Supported Program for the Strategic Research Foundation at Private Universities and a grant from the Japan Society for the Promotion of Science of the Ministry of Education, Culture, Sports, Science, and Technology. The authors report no relevant financial relationships. Dr. Holick reported grants from Carbogen Amcis and Solius; personal fees from Biogena, Sanofi, Faes Farma, Eric Anthony Nepute, and others; nonfinancial support from Ontometrics outside the submitted work; and had a patent for Novel Use of 25 hydroxy vitamin D pending for Carbogen Amcis BV and Aamanya AG.

A version of this article appeared on Medscape.com.

A team at Lyon’s Cancer Research Center (CRCL) has revealed the role of an enzyme, PRMT5, in the response to tamoxifen, a drug used to prevent relapse in premenopausal women with breast cancer. The protein could become the first predictive marker of response to tamoxifen.

Muriel Le Romancer, MD, director of research at France’s Institute of Health and Medical Research, explained the issues involved in this discovery in an interview. She jointly led this research along with Olivier Trédan, MD, PhD, oncologist at Lyon’s Léon Bérard Clinic. The research concluded with the publication of a study in EMBO Molecular Medicine. The researchers both head up the CRCL’s hormone resistance, methylation, and breast cancer team.

Although the enzyme’s involvement in the mode of action of tamoxifen has been observed in close to 900 patients with breast cancer, these results need to be validated in other at-risk patient cohorts before the biomarker can be considered for routine use, said Dr. Le Romancer. She estimated that 2 more years of research are needed.

Can you tell us which cases involve the use of tamoxifen and what its mode of action is?

Dr. Le Romancer: Tamoxifen is a hormone therapy used to reduce the risk of breast cancer relapse. It is prescribed to premenopausal women with hormone-sensitive cancer, which equates to roughly 25% of women with breast cancer: 15,000 women each year. The drug, which is taken every day via oral administration, is an estrogen antagonist. By binding to these receptors, it blocks estrogen from mediating its biological effect in the breasts. Aromatase inhibitors are the preferred choice in postmenopausal women, as they have been shown to be more effective. These also have an antiestrogenic effect, but by inhibiting estrogen production.

Tamoxifen therapy is prescribed for a minimum period of 5 years. Despite this, 25% of women treated with tamoxifen relapse. Tamoxifen resistance is unique in that it occurs very late on, generally 10-15 years after starting treatment. This means that it’s really important for us to identify predictive markers of the response to hormone therapy to adapt treatment as best we can. For the moment, the only criteria used to prescribe tamoxifen are patient age and the presence of estrogen receptors within the tumor.

Exactly how would treatment be improved if a decisive predictive marker of response to tamoxifen could be identified?

Dr. Le Romancer: Currently, when a patient’s breast cancer relapses after several years of treatment with tamoxifen, we don’t know if the relapse is linked to tamoxifen resistance or not. This makes it difficult to choose the right treatment to manage such relapses, which remain complicated to treat. Lots of patients die because of metastases.

By predicting the response to tamoxifen using a marker, we will be able to either use another hormone therapy to prevent the relapse or prescribe tamoxifen alongside a molecule that stops resistance from developing. We hope that this will significantly reduce the rate of relapse.

You put forward PRMT5 as a potential predictive marker of response to tamoxifen. What makes you think it could be used in this way?

Dr. Le Romancer: Our research has allowed us to demonstrate that PRMT5, when present in the nuclei of tumor cells, is involved in the mechanisms of action of tamoxifen. Remember that estrogen receptors are located in cell nuclei. For tamoxifen to exert its antitumoral action, PRMT5, an enzyme, needs to enter the nucleus to modify the estrogen receptor. It’s this modification that allows tamoxifen to inhibit tumor growth. The proliferative effect induced by the estrogens is also blocked.

The results of our study showed that high nuclear expression of PRMT5, specifically in the nuclei of breast cancer cells, is associated with a prolonged survival of tamoxifen-treated patients. Until now, we thought this enzyme had an oncogenic role when present in the cytoplasm. It turns out that it also has the opposite effect when acting within the nucleus, at least in this patient cohort: women with hormone-sensitive breast cancer treated with tamoxifen.

What are the next steps in your research before we can begin to think about its use in clinical practice?

Dr. Le Romancer: Our next research will focus on understanding the circumstances surrounding PRMT5 entering and leaving the nucleus. We have also shown that in some patients, tamoxifen causes PRMT5 to enter the cell nucleus. This translocation is only seen in women who respond to tamoxifen, not in those who are resistant to treatment with the drug. All that remains is for us to work out how tamoxifen facilitates this translocation.

Once the elements promoting this translocation have been identified, we will be able to propose a treatment aimed at forcing the enzyme to enter the nucleus and stay there. Eventually, the idea is to combine treatment with antiestrogens with a medicinal product that promotes localization of PRMT5 in the nucleus to guarantee response to tamoxifen. It will be a few years of research before we can apply our findings to clinical practice.

Could we use this biomarker as is just to identify tamoxifen resistance?

Dr. Le Romancer: In the short term, yes, we could use this biomarker to better guide treatment choices at time of diagnosis. We have demonstrated the role of PRMT5 in response to tamoxifen by studying two cohorts of 900 patients with breast cancer receiving treatment at the Léon Bérard Center, Lyon. Before moving on to routine testing, we need to replicate these results in other cohorts, especially in high-risk patients with, for example, greater cell proliferation or those who experience relapse.

The use of this biomarker is based on histological examination of cancer tissue. Single antibody tissue staining targeting PRMT5 reveals the localization of the enzyme in the cells and provides a score evaluating its presence in the nucleus. Using this score, it would be possible to determine the level of response to tamoxifen and decide whether the treatment should be used. This biomarker is the first of its kind undergoing validation as part of the examination of resistance to hormone therapy. We should be able to confirm the findings within the next 2 years.

If clinical tests using this biomarker predict tamoxifen resistance, what alternative treatments are available to these patients?

Dr. Le Romancer: We could give them an aromatase inhibitor or one of the new estrogen antagonists that are currently in development. In a phase 3 study, fulvestrant (Faslodex), for example, demonstrated a significant benefit in treating women with hormone-sensitive advanced breast cancer when administered via injection. The same goes for oral treatment, elacestrant (Orserdu), which has recently been approved by the Food and Drug Administration. These treatments are usually deemed second line after tamoxifen, but they could certainly be used as first-line therapy in resistant patients.

The results obtained from research into novel estrogen antagonists are certainly encouraging. Can tamoxifen retain its prominent position while still ensuring its efficacy?

Dr. Le Romancer: Keeping in mind the current trend for personalized medicine, we should keep as many treatment options open as possible. When a patient relapses, there need to be other treatments available to them. Tamoxifen has been ousted in favor of aromatase inhibitors for postmenopausal women, but it’s still the gold standard for premenopausal women and has been for over 20 years. Despite having been replaced by a novel estrogen antagonist, it will still have a prominent place in the therapeutic arsenal of premenopausal women with breast cancer.

With the development of PRMT5 as a predictive biomarker, we could even see tamoxifen being proposed as first-line therapy for postmenopausal women in whom high levels of PRMT5 are found in the nuclei of their cancer cells. By predicting their response, we could achieve greater efficacy of tamoxifen, compared with aromatase inhibitors. For now, this remains a hypothesis and must be verified in further clinical studies.

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

A team at Lyon’s Cancer Research Center (CRCL) has revealed the role of an enzyme, PRMT5, in the response to tamoxifen, a drug used to prevent relapse in premenopausal women with breast cancer. The protein could become the first predictive marker of response to tamoxifen.

Muriel Le Romancer, MD, director of research at France’s Institute of Health and Medical Research, explained the issues involved in this discovery in an interview. She jointly led this research along with Olivier Trédan, MD, PhD, oncologist at Lyon’s Léon Bérard Clinic. The research concluded with the publication of a study in EMBO Molecular Medicine. The researchers both head up the CRCL’s hormone resistance, methylation, and breast cancer team.

Although the enzyme’s involvement in the mode of action of tamoxifen has been observed in close to 900 patients with breast cancer, these results need to be validated in other at-risk patient cohorts before the biomarker can be considered for routine use, said Dr. Le Romancer. She estimated that 2 more years of research are needed.

Can you tell us which cases involve the use of tamoxifen and what its mode of action is?

Dr. Le Romancer: Tamoxifen is a hormone therapy used to reduce the risk of breast cancer relapse. It is prescribed to premenopausal women with hormone-sensitive cancer, which equates to roughly 25% of women with breast cancer: 15,000 women each year. The drug, which is taken every day via oral administration, is an estrogen antagonist. By binding to these receptors, it blocks estrogen from mediating its biological effect in the breasts. Aromatase inhibitors are the preferred choice in postmenopausal women, as they have been shown to be more effective. These also have an antiestrogenic effect, but by inhibiting estrogen production.

Tamoxifen therapy is prescribed for a minimum period of 5 years. Despite this, 25% of women treated with tamoxifen relapse. Tamoxifen resistance is unique in that it occurs very late on, generally 10-15 years after starting treatment. This means that it’s really important for us to identify predictive markers of the response to hormone therapy to adapt treatment as best we can. For the moment, the only criteria used to prescribe tamoxifen are patient age and the presence of estrogen receptors within the tumor.

Exactly how would treatment be improved if a decisive predictive marker of response to tamoxifen could be identified?

Dr. Le Romancer: Currently, when a patient’s breast cancer relapses after several years of treatment with tamoxifen, we don’t know if the relapse is linked to tamoxifen resistance or not. This makes it difficult to choose the right treatment to manage such relapses, which remain complicated to treat. Lots of patients die because of metastases.

By predicting the response to tamoxifen using a marker, we will be able to either use another hormone therapy to prevent the relapse or prescribe tamoxifen alongside a molecule that stops resistance from developing. We hope that this will significantly reduce the rate of relapse.

You put forward PRMT5 as a potential predictive marker of response to tamoxifen. What makes you think it could be used in this way?

Dr. Le Romancer: Our research has allowed us to demonstrate that PRMT5, when present in the nuclei of tumor cells, is involved in the mechanisms of action of tamoxifen. Remember that estrogen receptors are located in cell nuclei. For tamoxifen to exert its antitumoral action, PRMT5, an enzyme, needs to enter the nucleus to modify the estrogen receptor. It’s this modification that allows tamoxifen to inhibit tumor growth. The proliferative effect induced by the estrogens is also blocked.

The results of our study showed that high nuclear expression of PRMT5, specifically in the nuclei of breast cancer cells, is associated with a prolonged survival of tamoxifen-treated patients. Until now, we thought this enzyme had an oncogenic role when present in the cytoplasm. It turns out that it also has the opposite effect when acting within the nucleus, at least in this patient cohort: women with hormone-sensitive breast cancer treated with tamoxifen.

What are the next steps in your research before we can begin to think about its use in clinical practice?

Dr. Le Romancer: Our next research will focus on understanding the circumstances surrounding PRMT5 entering and leaving the nucleus. We have also shown that in some patients, tamoxifen causes PRMT5 to enter the cell nucleus. This translocation is only seen in women who respond to tamoxifen, not in those who are resistant to treatment with the drug. All that remains is for us to work out how tamoxifen facilitates this translocation.

Once the elements promoting this translocation have been identified, we will be able to propose a treatment aimed at forcing the enzyme to enter the nucleus and stay there. Eventually, the idea is to combine treatment with antiestrogens with a medicinal product that promotes localization of PRMT5 in the nucleus to guarantee response to tamoxifen. It will be a few years of research before we can apply our findings to clinical practice.

Could we use this biomarker as is just to identify tamoxifen resistance?

Dr. Le Romancer: In the short term, yes, we could use this biomarker to better guide treatment choices at time of diagnosis. We have demonstrated the role of PRMT5 in response to tamoxifen by studying two cohorts of 900 patients with breast cancer receiving treatment at the Léon Bérard Center, Lyon. Before moving on to routine testing, we need to replicate these results in other cohorts, especially in high-risk patients with, for example, greater cell proliferation or those who experience relapse.

The use of this biomarker is based on histological examination of cancer tissue. Single antibody tissue staining targeting PRMT5 reveals the localization of the enzyme in the cells and provides a score evaluating its presence in the nucleus. Using this score, it would be possible to determine the level of response to tamoxifen and decide whether the treatment should be used. This biomarker is the first of its kind undergoing validation as part of the examination of resistance to hormone therapy. We should be able to confirm the findings within the next 2 years.

If clinical tests using this biomarker predict tamoxifen resistance, what alternative treatments are available to these patients?

Dr. Le Romancer: We could give them an aromatase inhibitor or one of the new estrogen antagonists that are currently in development. In a phase 3 study, fulvestrant (Faslodex), for example, demonstrated a significant benefit in treating women with hormone-sensitive advanced breast cancer when administered via injection. The same goes for oral treatment, elacestrant (Orserdu), which has recently been approved by the Food and Drug Administration. These treatments are usually deemed second line after tamoxifen, but they could certainly be used as first-line therapy in resistant patients.

The results obtained from research into novel estrogen antagonists are certainly encouraging. Can tamoxifen retain its prominent position while still ensuring its efficacy?

Dr. Le Romancer: Keeping in mind the current trend for personalized medicine, we should keep as many treatment options open as possible. When a patient relapses, there need to be other treatments available to them. Tamoxifen has been ousted in favor of aromatase inhibitors for postmenopausal women, but it’s still the gold standard for premenopausal women and has been for over 20 years. Despite having been replaced by a novel estrogen antagonist, it will still have a prominent place in the therapeutic arsenal of premenopausal women with breast cancer.

With the development of PRMT5 as a predictive biomarker, we could even see tamoxifen being proposed as first-line therapy for postmenopausal women in whom high levels of PRMT5 are found in the nuclei of their cancer cells. By predicting their response, we could achieve greater efficacy of tamoxifen, compared with aromatase inhibitors. For now, this remains a hypothesis and must be verified in further clinical studies.

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

A team at Lyon’s Cancer Research Center (CRCL) has revealed the role of an enzyme, PRMT5, in the response to tamoxifen, a drug used to prevent relapse in premenopausal women with breast cancer. The protein could become the first predictive marker of response to tamoxifen.

Muriel Le Romancer, MD, director of research at France’s Institute of Health and Medical Research, explained the issues involved in this discovery in an interview. She jointly led this research along with Olivier Trédan, MD, PhD, oncologist at Lyon’s Léon Bérard Clinic. The research concluded with the publication of a study in EMBO Molecular Medicine. The researchers both head up the CRCL’s hormone resistance, methylation, and breast cancer team.

Although the enzyme’s involvement in the mode of action of tamoxifen has been observed in close to 900 patients with breast cancer, these results need to be validated in other at-risk patient cohorts before the biomarker can be considered for routine use, said Dr. Le Romancer. She estimated that 2 more years of research are needed.

Can you tell us which cases involve the use of tamoxifen and what its mode of action is?

Dr. Le Romancer: Tamoxifen is a hormone therapy used to reduce the risk of breast cancer relapse. It is prescribed to premenopausal women with hormone-sensitive cancer, which equates to roughly 25% of women with breast cancer: 15,000 women each year. The drug, which is taken every day via oral administration, is an estrogen antagonist. By binding to these receptors, it blocks estrogen from mediating its biological effect in the breasts. Aromatase inhibitors are the preferred choice in postmenopausal women, as they have been shown to be more effective. These also have an antiestrogenic effect, but by inhibiting estrogen production.

Tamoxifen therapy is prescribed for a minimum period of 5 years. Despite this, 25% of women treated with tamoxifen relapse. Tamoxifen resistance is unique in that it occurs very late on, generally 10-15 years after starting treatment. This means that it’s really important for us to identify predictive markers of the response to hormone therapy to adapt treatment as best we can. For the moment, the only criteria used to prescribe tamoxifen are patient age and the presence of estrogen receptors within the tumor.

Exactly how would treatment be improved if a decisive predictive marker of response to tamoxifen could be identified?

Dr. Le Romancer: Currently, when a patient’s breast cancer relapses after several years of treatment with tamoxifen, we don’t know if the relapse is linked to tamoxifen resistance or not. This makes it difficult to choose the right treatment to manage such relapses, which remain complicated to treat. Lots of patients die because of metastases.

By predicting the response to tamoxifen using a marker, we will be able to either use another hormone therapy to prevent the relapse or prescribe tamoxifen alongside a molecule that stops resistance from developing. We hope that this will significantly reduce the rate of relapse.

You put forward PRMT5 as a potential predictive marker of response to tamoxifen. What makes you think it could be used in this way?

Dr. Le Romancer: Our research has allowed us to demonstrate that PRMT5, when present in the nuclei of tumor cells, is involved in the mechanisms of action of tamoxifen. Remember that estrogen receptors are located in cell nuclei. For tamoxifen to exert its antitumoral action, PRMT5, an enzyme, needs to enter the nucleus to modify the estrogen receptor. It’s this modification that allows tamoxifen to inhibit tumor growth. The proliferative effect induced by the estrogens is also blocked.

The results of our study showed that high nuclear expression of PRMT5, specifically in the nuclei of breast cancer cells, is associated with a prolonged survival of tamoxifen-treated patients. Until now, we thought this enzyme had an oncogenic role when present in the cytoplasm. It turns out that it also has the opposite effect when acting within the nucleus, at least in this patient cohort: women with hormone-sensitive breast cancer treated with tamoxifen.

What are the next steps in your research before we can begin to think about its use in clinical practice?

Dr. Le Romancer: Our next research will focus on understanding the circumstances surrounding PRMT5 entering and leaving the nucleus. We have also shown that in some patients, tamoxifen causes PRMT5 to enter the cell nucleus. This translocation is only seen in women who respond to tamoxifen, not in those who are resistant to treatment with the drug. All that remains is for us to work out how tamoxifen facilitates this translocation.

Once the elements promoting this translocation have been identified, we will be able to propose a treatment aimed at forcing the enzyme to enter the nucleus and stay there. Eventually, the idea is to combine treatment with antiestrogens with a medicinal product that promotes localization of PRMT5 in the nucleus to guarantee response to tamoxifen. It will be a few years of research before we can apply our findings to clinical practice.

Could we use this biomarker as is just to identify tamoxifen resistance?

Dr. Le Romancer: In the short term, yes, we could use this biomarker to better guide treatment choices at time of diagnosis. We have demonstrated the role of PRMT5 in response to tamoxifen by studying two cohorts of 900 patients with breast cancer receiving treatment at the Léon Bérard Center, Lyon. Before moving on to routine testing, we need to replicate these results in other cohorts, especially in high-risk patients with, for example, greater cell proliferation or those who experience relapse.

The use of this biomarker is based on histological examination of cancer tissue. Single antibody tissue staining targeting PRMT5 reveals the localization of the enzyme in the cells and provides a score evaluating its presence in the nucleus. Using this score, it would be possible to determine the level of response to tamoxifen and decide whether the treatment should be used. This biomarker is the first of its kind undergoing validation as part of the examination of resistance to hormone therapy. We should be able to confirm the findings within the next 2 years.

If clinical tests using this biomarker predict tamoxifen resistance, what alternative treatments are available to these patients?

Dr. Le Romancer: We could give them an aromatase inhibitor or one of the new estrogen antagonists that are currently in development. In a phase 3 study, fulvestrant (Faslodex), for example, demonstrated a significant benefit in treating women with hormone-sensitive advanced breast cancer when administered via injection. The same goes for oral treatment, elacestrant (Orserdu), which has recently been approved by the Food and Drug Administration. These treatments are usually deemed second line after tamoxifen, but they could certainly be used as first-line therapy in resistant patients.

The results obtained from research into novel estrogen antagonists are certainly encouraging. Can tamoxifen retain its prominent position while still ensuring its efficacy?

Dr. Le Romancer: Keeping in mind the current trend for personalized medicine, we should keep as many treatment options open as possible. When a patient relapses, there need to be other treatments available to them. Tamoxifen has been ousted in favor of aromatase inhibitors for postmenopausal women, but it’s still the gold standard for premenopausal women and has been for over 20 years. Despite having been replaced by a novel estrogen antagonist, it will still have a prominent place in the therapeutic arsenal of premenopausal women with breast cancer.

With the development of PRMT5 as a predictive biomarker, we could even see tamoxifen being proposed as first-line therapy for postmenopausal women in whom high levels of PRMT5 are found in the nuclei of their cancer cells. By predicting their response, we could achieve greater efficacy of tamoxifen, compared with aromatase inhibitors. For now, this remains a hypothesis and must be verified in further clinical studies.

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

Pediatric patients receiving donor stem cell transplantion with healthier pretransplant gut microbiota diversity show improved rates of survival and a lower risk of developing acute graft versus host disease (GvHD), similar to the patterns reported in adults.

“To the best of our knowledge, we present the first evidence of an association between pretransplantation lower gut microbiota diversity and poorer outcome in children undergoing allo-HSCT,” the authors report, in research published in the journal Blood. “Our findings underscore the importance of pre-transplant gut microbiota diversity and compositional structure in influencing allo-HSCT-related clinical outcomes in the pediatric setting.”

While allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be potentially curative of hematologic malignancies, the stem cell transplantation process can wreak havoc on gut microbiota, because of factors including the conditioning regimen, antibiotic exposure, and dietary changes.

Specifically, the process can cause a substantial decrease in necessary alpha diversity and a potential expansion of possibly pathogenic bacteria.

While poor gut microbiota diversity has been linked to higher mortality in adult patients receiving allo-HSCT, research on the effects in pediatric patients is lacking.

“The gut microbiota of children differs from adults’ one, and this accounts for the need for specific pediatric studies on the gut microbiota-to–allo-HSCT relationship,” the authors write.

For the multicenter study, first author Riccardo Masetti, MD, PhD, of the department of pediatric oncology and hematology at the University of Bologna, Italy, and colleagues analyzed the gut microbiota diversity of 90 pediatric allo-HSCT recipients at four centers in Italy and one in Poland, stratifying the patients into groups of higher and lower diversity pretransplantation and again at the time of neutrophil engraftment.

Overall, gut microbiota diversity significantly declined from before allo-HSCT to afterward, at the time of neutrophil engraftment (P < .0001), with lower diversity observed in patients 3 years of age or younger.

With a median follow-up of 52 months, compared with the lower diversity group, those with higher diversity prior to transplantation had a significantly higher probability of overall survival (hazard ratio, 0.26; P = .011), after adjustment for age, graft source, donor type, intensity of conditioning regimen, center, and type of disease, with estimated overall survival at 52 months after allo-HSCT of 88.9% for the higher diversity group and 62.7% for the lower diversity group.

The cumulative incidence of grade II-IV acute GvHD was significantly lower for the higher diversity group versus lower diversity (20.0 versus 44.4, respectively; P = .017), as were the incidence rates of grade III-IV acute GvHD (2.2 versus 20.0; P = .007).

There were, however, no significant differences between the low and high diversity gut microbiota groups in relapse-free survival (P = .091).

The higher diversity group notably had higher relative abundances of potentially health-related bacterial families, including Ruminococcaceae and Oscillospiraceae, while the lower diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae.

Of note, the results differ from those observed in adults, among whom gut microbiota diversity before as well as after transplantation has been significantly associated with transplant outcomes, whereas with children, the association was limited to diversity prior to transplant.

In general, children have significantly lower diversity of gut microbiota than adults, with varying functional properties, and microbiota that is more easily modified by environmental factors, with larger changes occurring upon exposure to external stressors, the authors explain.

“Considering these different ecological properties compared to adults, we hypothesize that allo-HSCT–induced dysbiosis in the pediatric setting may imply loss of age-related gut microbiota signatures, including alpha diversity, with high interpatient variability,” they say.

Characteristics that were associated with higher or lower gut microbiota diversity prior to allo-HSCT included the treating center, suggesting that the geographical region may affect the diversity and the type of antibiotic exposure prior to the transplant.

Limitations included that “we didn’t assess other pretransplant characteristics such as the type of chemotherapy received, or the lifestyle, and this should be addressed in future studies on larger cohorts,” Dr. Masetti said in an interview.

While lengthy delays in screening of samples are barriers in the use of the gut microbiome as a tool in clinical practice, he noted that clinicians can take key measures to improve the microbiota.

“[Preventive measures] include the avoidance of unnecessary antibiotic treatment, which has a detrimental effect on the microbiota,” he said. “Moreover, some dietary changes may promote microbiota health.”

In addition, key measures can be taken during the allo-HSCT to preserve the microbiota, he added.

“In our center, we use enteral nutrition with a nasogastric tube rather than parenteral nutrition, which helps the microbiota to recover faster,” Dr. Masetti explained. “Moreover, other interventional measures such as fecal microbiota transplantation or the use of probiotics are under testing.”

“In particular, our data emphasize the importance of an overall healthy network, rather than the abundance of specific families or genera, in preventing complications and unfavorable outcomes.”

Commenting on the study, Robert Jenq, MD, an assistant professor in the departments of genomic medicine and stem cell transplantation and cellular therapy at the University of Texas M.D. Anderson Cancer Center, Houston, noted that with the growing evidence of the effects of poor gut microbiota diversity on clinical outcomes, multiple early-phase clinical trials are being conducted to test various strategies to prevent or treat gut injury.

“I’m not aware of any one approach that has shown enough promise to warrant being tested in multicenter studies yet, but it’s still a bit early,” Dr. Jenq said.“In the meantime, discontinuing or de-escalating antibiotics when medically safe, and encouraging patients to eat as much as they’re able to is a reasonable recommendation.”

Dr. Jenq added that, with most of the data on the issue being retrospective, a causative role has not been established, and “the finding of an association between the gut microbiota composition and survival, while interesting and provocative, does not provide evidence that intervening on the gut microbiota will lead to a clinical benefit.”

“I’m hopeful that randomized clinical trials will eventually demonstrate that we can protect or restore the gut microbiota, and this will lead to substantial clinical benefits, but this remains to be seen,” he said.

The authors had no disclosures to report. Dr. Jenq is an advisor for Seres Therapeutics, Prolacta Biosciences, and MaaT Pharma.

Pediatric patients receiving donor stem cell transplantion with healthier pretransplant gut microbiota diversity show improved rates of survival and a lower risk of developing acute graft versus host disease (GvHD), similar to the patterns reported in adults.

“To the best of our knowledge, we present the first evidence of an association between pretransplantation lower gut microbiota diversity and poorer outcome in children undergoing allo-HSCT,” the authors report, in research published in the journal Blood. “Our findings underscore the importance of pre-transplant gut microbiota diversity and compositional structure in influencing allo-HSCT-related clinical outcomes in the pediatric setting.”

While allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be potentially curative of hematologic malignancies, the stem cell transplantation process can wreak havoc on gut microbiota, because of factors including the conditioning regimen, antibiotic exposure, and dietary changes.

Specifically, the process can cause a substantial decrease in necessary alpha diversity and a potential expansion of possibly pathogenic bacteria.

While poor gut microbiota diversity has been linked to higher mortality in adult patients receiving allo-HSCT, research on the effects in pediatric patients is lacking.

“The gut microbiota of children differs from adults’ one, and this accounts for the need for specific pediatric studies on the gut microbiota-to–allo-HSCT relationship,” the authors write.

For the multicenter study, first author Riccardo Masetti, MD, PhD, of the department of pediatric oncology and hematology at the University of Bologna, Italy, and colleagues analyzed the gut microbiota diversity of 90 pediatric allo-HSCT recipients at four centers in Italy and one in Poland, stratifying the patients into groups of higher and lower diversity pretransplantation and again at the time of neutrophil engraftment.

Overall, gut microbiota diversity significantly declined from before allo-HSCT to afterward, at the time of neutrophil engraftment (P < .0001), with lower diversity observed in patients 3 years of age or younger.

With a median follow-up of 52 months, compared with the lower diversity group, those with higher diversity prior to transplantation had a significantly higher probability of overall survival (hazard ratio, 0.26; P = .011), after adjustment for age, graft source, donor type, intensity of conditioning regimen, center, and type of disease, with estimated overall survival at 52 months after allo-HSCT of 88.9% for the higher diversity group and 62.7% for the lower diversity group.

The cumulative incidence of grade II-IV acute GvHD was significantly lower for the higher diversity group versus lower diversity (20.0 versus 44.4, respectively; P = .017), as were the incidence rates of grade III-IV acute GvHD (2.2 versus 20.0; P = .007).

There were, however, no significant differences between the low and high diversity gut microbiota groups in relapse-free survival (P = .091).

The higher diversity group notably had higher relative abundances of potentially health-related bacterial families, including Ruminococcaceae and Oscillospiraceae, while the lower diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae.

Of note, the results differ from those observed in adults, among whom gut microbiota diversity before as well as after transplantation has been significantly associated with transplant outcomes, whereas with children, the association was limited to diversity prior to transplant.

In general, children have significantly lower diversity of gut microbiota than adults, with varying functional properties, and microbiota that is more easily modified by environmental factors, with larger changes occurring upon exposure to external stressors, the authors explain.

“Considering these different ecological properties compared to adults, we hypothesize that allo-HSCT–induced dysbiosis in the pediatric setting may imply loss of age-related gut microbiota signatures, including alpha diversity, with high interpatient variability,” they say.

Characteristics that were associated with higher or lower gut microbiota diversity prior to allo-HSCT included the treating center, suggesting that the geographical region may affect the diversity and the type of antibiotic exposure prior to the transplant.

Limitations included that “we didn’t assess other pretransplant characteristics such as the type of chemotherapy received, or the lifestyle, and this should be addressed in future studies on larger cohorts,” Dr. Masetti said in an interview.

While lengthy delays in screening of samples are barriers in the use of the gut microbiome as a tool in clinical practice, he noted that clinicians can take key measures to improve the microbiota.

“[Preventive measures] include the avoidance of unnecessary antibiotic treatment, which has a detrimental effect on the microbiota,” he said. “Moreover, some dietary changes may promote microbiota health.”

In addition, key measures can be taken during the allo-HSCT to preserve the microbiota, he added.

“In our center, we use enteral nutrition with a nasogastric tube rather than parenteral nutrition, which helps the microbiota to recover faster,” Dr. Masetti explained. “Moreover, other interventional measures such as fecal microbiota transplantation or the use of probiotics are under testing.”

“In particular, our data emphasize the importance of an overall healthy network, rather than the abundance of specific families or genera, in preventing complications and unfavorable outcomes.”

Commenting on the study, Robert Jenq, MD, an assistant professor in the departments of genomic medicine and stem cell transplantation and cellular therapy at the University of Texas M.D. Anderson Cancer Center, Houston, noted that with the growing evidence of the effects of poor gut microbiota diversity on clinical outcomes, multiple early-phase clinical trials are being conducted to test various strategies to prevent or treat gut injury.

“I’m not aware of any one approach that has shown enough promise to warrant being tested in multicenter studies yet, but it’s still a bit early,” Dr. Jenq said.“In the meantime, discontinuing or de-escalating antibiotics when medically safe, and encouraging patients to eat as much as they’re able to is a reasonable recommendation.”

Dr. Jenq added that, with most of the data on the issue being retrospective, a causative role has not been established, and “the finding of an association between the gut microbiota composition and survival, while interesting and provocative, does not provide evidence that intervening on the gut microbiota will lead to a clinical benefit.”

“I’m hopeful that randomized clinical trials will eventually demonstrate that we can protect or restore the gut microbiota, and this will lead to substantial clinical benefits, but this remains to be seen,” he said.

The authors had no disclosures to report. Dr. Jenq is an advisor for Seres Therapeutics, Prolacta Biosciences, and MaaT Pharma.

Pediatric patients receiving donor stem cell transplantion with healthier pretransplant gut microbiota diversity show improved rates of survival and a lower risk of developing acute graft versus host disease (GvHD), similar to the patterns reported in adults.

“To the best of our knowledge, we present the first evidence of an association between pretransplantation lower gut microbiota diversity and poorer outcome in children undergoing allo-HSCT,” the authors report, in research published in the journal Blood. “Our findings underscore the importance of pre-transplant gut microbiota diversity and compositional structure in influencing allo-HSCT-related clinical outcomes in the pediatric setting.”

While allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be potentially curative of hematologic malignancies, the stem cell transplantation process can wreak havoc on gut microbiota, because of factors including the conditioning regimen, antibiotic exposure, and dietary changes.

Specifically, the process can cause a substantial decrease in necessary alpha diversity and a potential expansion of possibly pathogenic bacteria.

While poor gut microbiota diversity has been linked to higher mortality in adult patients receiving allo-HSCT, research on the effects in pediatric patients is lacking.

“The gut microbiota of children differs from adults’ one, and this accounts for the need for specific pediatric studies on the gut microbiota-to–allo-HSCT relationship,” the authors write.

For the multicenter study, first author Riccardo Masetti, MD, PhD, of the department of pediatric oncology and hematology at the University of Bologna, Italy, and colleagues analyzed the gut microbiota diversity of 90 pediatric allo-HSCT recipients at four centers in Italy and one in Poland, stratifying the patients into groups of higher and lower diversity pretransplantation and again at the time of neutrophil engraftment.

Overall, gut microbiota diversity significantly declined from before allo-HSCT to afterward, at the time of neutrophil engraftment (P < .0001), with lower diversity observed in patients 3 years of age or younger.

With a median follow-up of 52 months, compared with the lower diversity group, those with higher diversity prior to transplantation had a significantly higher probability of overall survival (hazard ratio, 0.26; P = .011), after adjustment for age, graft source, donor type, intensity of conditioning regimen, center, and type of disease, with estimated overall survival at 52 months after allo-HSCT of 88.9% for the higher diversity group and 62.7% for the lower diversity group.

The cumulative incidence of grade II-IV acute GvHD was significantly lower for the higher diversity group versus lower diversity (20.0 versus 44.4, respectively; P = .017), as were the incidence rates of grade III-IV acute GvHD (2.2 versus 20.0; P = .007).

There were, however, no significant differences between the low and high diversity gut microbiota groups in relapse-free survival (P = .091).

The higher diversity group notably had higher relative abundances of potentially health-related bacterial families, including Ruminococcaceae and Oscillospiraceae, while the lower diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae.

Of note, the results differ from those observed in adults, among whom gut microbiota diversity before as well as after transplantation has been significantly associated with transplant outcomes, whereas with children, the association was limited to diversity prior to transplant.

In general, children have significantly lower diversity of gut microbiota than adults, with varying functional properties, and microbiota that is more easily modified by environmental factors, with larger changes occurring upon exposure to external stressors, the authors explain.

“Considering these different ecological properties compared to adults, we hypothesize that allo-HSCT–induced dysbiosis in the pediatric setting may imply loss of age-related gut microbiota signatures, including alpha diversity, with high interpatient variability,” they say.

Characteristics that were associated with higher or lower gut microbiota diversity prior to allo-HSCT included the treating center, suggesting that the geographical region may affect the diversity and the type of antibiotic exposure prior to the transplant.

Limitations included that “we didn’t assess other pretransplant characteristics such as the type of chemotherapy received, or the lifestyle, and this should be addressed in future studies on larger cohorts,” Dr. Masetti said in an interview.

While lengthy delays in screening of samples are barriers in the use of the gut microbiome as a tool in clinical practice, he noted that clinicians can take key measures to improve the microbiota.

“[Preventive measures] include the avoidance of unnecessary antibiotic treatment, which has a detrimental effect on the microbiota,” he said. “Moreover, some dietary changes may promote microbiota health.”

In addition, key measures can be taken during the allo-HSCT to preserve the microbiota, he added.

“In our center, we use enteral nutrition with a nasogastric tube rather than parenteral nutrition, which helps the microbiota to recover faster,” Dr. Masetti explained. “Moreover, other interventional measures such as fecal microbiota transplantation or the use of probiotics are under testing.”

“In particular, our data emphasize the importance of an overall healthy network, rather than the abundance of specific families or genera, in preventing complications and unfavorable outcomes.”

Commenting on the study, Robert Jenq, MD, an assistant professor in the departments of genomic medicine and stem cell transplantation and cellular therapy at the University of Texas M.D. Anderson Cancer Center, Houston, noted that with the growing evidence of the effects of poor gut microbiota diversity on clinical outcomes, multiple early-phase clinical trials are being conducted to test various strategies to prevent or treat gut injury.

“I’m not aware of any one approach that has shown enough promise to warrant being tested in multicenter studies yet, but it’s still a bit early,” Dr. Jenq said.“In the meantime, discontinuing or de-escalating antibiotics when medically safe, and encouraging patients to eat as much as they’re able to is a reasonable recommendation.”

Dr. Jenq added that, with most of the data on the issue being retrospective, a causative role has not been established, and “the finding of an association between the gut microbiota composition and survival, while interesting and provocative, does not provide evidence that intervening on the gut microbiota will lead to a clinical benefit.”

“I’m hopeful that randomized clinical trials will eventually demonstrate that we can protect or restore the gut microbiota, and this will lead to substantial clinical benefits, but this remains to be seen,” he said.

The authors had no disclosures to report. Dr. Jenq is an advisor for Seres Therapeutics, Prolacta Biosciences, and MaaT Pharma.

Alcohol consumption, including risky drinking behaviors, is common among adult cancer survivors, even people currently receiving cancer treatment, new research shows.

An analysis of more than 15,000 adults with a cancer diagnosis revealed that nearly 80% were current drinkers. Among current drinkers, 13% consumed a moderate amount of alcohol in a typical day, while close to 40% engaged in hazardous drinking.

The numbers are “staggering,” Yin Cao, ScD, MPH, of Washington University in St. Louis, said in an interview. “Most concerning is that those on cancer treatment are engaged in a similar level of risky drinking.”

The study was published online in JAMA Network Open.

Drinking alcohol can increase a person’s risk for a variety of cancers, including oral and pharyngeal cancer as well as esophageal, colorectal, liver, and female breast cancers.

Consuming alcohol is also associated with numerous risks among people diagnosed with cancer. In the short term, alcohol consumption can worsen postsurgical outcomes as well as impair cognition and amplify cardiotoxicity in patients undergoing chemotherapy. In the long term, drinking alcohol can elevate a person’s risk of recurrence, secondary tumors, and mortality.

The American Society of Clinical Oncology recently issued a statement reinforcing the need to prioritize alcohol consumption as a key modifiable behavioral factor in the cancer control research agenda.

The current American Cancer Society guidelines indicate that it’s best to avoid or, at least, minimize alcohol consumption. Men should limit their intake to no more than two drinks per day and women should have no more than one drink per day.

Despite this data and guidelines, alcohol drinking patterns among cancer survivors in the United States remain poorly understood.

To explore further, the researchers identified 15,199 adult cancer survivors enrolled in the National Institutes of Health’s All of Us Research Program.

Overall, 78% of the cohort – more than 11,800 individuals – were current drinkers. In a typical day, 24% engaged in binge drinking – consuming six or more drinks on a single occasion – and 38% engaged in hazardous drinking. Using the Alcohol Use Disorders Identification Test–Consumption, the researchers classified hazardous drinking as scores of 4 or higher in men and 3 or higher in women.

Drinking patterns looked similar in the subset of 1,839 patients undergoing cancer treatment. In this group, 76% were current drinkers. Among current drinkers, 12% exceeded moderate drinking levels, 23% reported binge drinking, and 38% engaged in hazardous drinking. In this group, men, Hispanics, people diagnosed with cancer before age 18, and smokers were more likely to engage in risky drinking behaviors.

“We know that many people who are diagnosed with cancer continue to drink alcohol, but this study provides much more detailed information about that,” said Farhad Islami, MD, PhD, senior scientific director for cancer disparity research at the American Cancer Society, Atlanta, who was not involved in the study.

Given the degree of drinking identified in this population, Dr. Cao highlighted the importance of talking to patients about alcohol.

“Our findings highlight an opportunity for enhanced support and intervention concerning risky drinking behaviors” in oncology, Dr. Cao said. “Given the societal norms surrounding alcohol and the general lack of awareness of alcohol’s short- and long-term impact on cancer outcomes, gently educating patients/survivors about potential risks while understanding the cultural and societal contexts of drinking can make a difference.”

Dr. Islami agreed that oncologists should talk to their patients about alcohol, “especially those going through active treatment because alcohol may affect the treatment or may be associated with more complications of the treatment.”

“Many people now know that smoking causes cancer, but unfortunately, many people do not know about the association of alcohol with cancer,” he said.

Outside of an awareness gap, there are numerous risk factors for substance abuse among cancer survivors, Marleen Meyers, MD, director of the cancer survivorship program at NYU Langone Perlmutter Cancer Center, New York, explained.

Alcohol can help some cancer survivors dull feelings of isolation, fear, stress, and poor pain management that may accompany their diagnosis and treatment, said Dr. Meyers, who was not involved in the research. That is why “it is important for patients to be honest with their providers and for providers to ask about substance use in a nonjudgmental way.”

In these conversations, oncologists should educate patients about the safety risks associated with alcohol intake during or after treatment and that there is no established “safe” amount of alcohol. Incorporating a mental health screening and questions about a family history of substance abuse can also help identify patients “most at risk so providers can be proactive,” she said.

The study was supported by a grant from the NIH. Dr. Cao, Dr. Islami, and Dr. Meyers report no relevant financial relationships.

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

Alcohol consumption, including risky drinking behaviors, is common among adult cancer survivors, even people currently receiving cancer treatment, new research shows.

An analysis of more than 15,000 adults with a cancer diagnosis revealed that nearly 80% were current drinkers. Among current drinkers, 13% consumed a moderate amount of alcohol in a typical day, while close to 40% engaged in hazardous drinking.

The numbers are “staggering,” Yin Cao, ScD, MPH, of Washington University in St. Louis, said in an interview. “Most concerning is that those on cancer treatment are engaged in a similar level of risky drinking.”

The study was published online in JAMA Network Open.

Drinking alcohol can increase a person’s risk for a variety of cancers, including oral and pharyngeal cancer as well as esophageal, colorectal, liver, and female breast cancers.

Consuming alcohol is also associated with numerous risks among people diagnosed with cancer. In the short term, alcohol consumption can worsen postsurgical outcomes as well as impair cognition and amplify cardiotoxicity in patients undergoing chemotherapy. In the long term, drinking alcohol can elevate a person’s risk of recurrence, secondary tumors, and mortality.

The American Society of Clinical Oncology recently issued a statement reinforcing the need to prioritize alcohol consumption as a key modifiable behavioral factor in the cancer control research agenda.

The current American Cancer Society guidelines indicate that it’s best to avoid or, at least, minimize alcohol consumption. Men should limit their intake to no more than two drinks per day and women should have no more than one drink per day.

Despite this data and guidelines, alcohol drinking patterns among cancer survivors in the United States remain poorly understood.

To explore further, the researchers identified 15,199 adult cancer survivors enrolled in the National Institutes of Health’s All of Us Research Program.

Overall, 78% of the cohort – more than 11,800 individuals – were current drinkers. In a typical day, 24% engaged in binge drinking – consuming six or more drinks on a single occasion – and 38% engaged in hazardous drinking. Using the Alcohol Use Disorders Identification Test–Consumption, the researchers classified hazardous drinking as scores of 4 or higher in men and 3 or higher in women.

Drinking patterns looked similar in the subset of 1,839 patients undergoing cancer treatment. In this group, 76% were current drinkers. Among current drinkers, 12% exceeded moderate drinking levels, 23% reported binge drinking, and 38% engaged in hazardous drinking. In this group, men, Hispanics, people diagnosed with cancer before age 18, and smokers were more likely to engage in risky drinking behaviors.

“We know that many people who are diagnosed with cancer continue to drink alcohol, but this study provides much more detailed information about that,” said Farhad Islami, MD, PhD, senior scientific director for cancer disparity research at the American Cancer Society, Atlanta, who was not involved in the study.

Given the degree of drinking identified in this population, Dr. Cao highlighted the importance of talking to patients about alcohol.

“Our findings highlight an opportunity for enhanced support and intervention concerning risky drinking behaviors” in oncology, Dr. Cao said. “Given the societal norms surrounding alcohol and the general lack of awareness of alcohol’s short- and long-term impact on cancer outcomes, gently educating patients/survivors about potential risks while understanding the cultural and societal contexts of drinking can make a difference.”

Dr. Islami agreed that oncologists should talk to their patients about alcohol, “especially those going through active treatment because alcohol may affect the treatment or may be associated with more complications of the treatment.”

“Many people now know that smoking causes cancer, but unfortunately, many people do not know about the association of alcohol with cancer,” he said.

Outside of an awareness gap, there are numerous risk factors for substance abuse among cancer survivors, Marleen Meyers, MD, director of the cancer survivorship program at NYU Langone Perlmutter Cancer Center, New York, explained.

Alcohol can help some cancer survivors dull feelings of isolation, fear, stress, and poor pain management that may accompany their diagnosis and treatment, said Dr. Meyers, who was not involved in the research. That is why “it is important for patients to be honest with their providers and for providers to ask about substance use in a nonjudgmental way.”

In these conversations, oncologists should educate patients about the safety risks associated with alcohol intake during or after treatment and that there is no established “safe” amount of alcohol. Incorporating a mental health screening and questions about a family history of substance abuse can also help identify patients “most at risk so providers can be proactive,” she said.

The study was supported by a grant from the NIH. Dr. Cao, Dr. Islami, and Dr. Meyers report no relevant financial relationships.

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

Alcohol consumption, including risky drinking behaviors, is common among adult cancer survivors, even people currently receiving cancer treatment, new research shows.

An analysis of more than 15,000 adults with a cancer diagnosis revealed that nearly 80% were current drinkers. Among current drinkers, 13% consumed a moderate amount of alcohol in a typical day, while close to 40% engaged in hazardous drinking.

The numbers are “staggering,” Yin Cao, ScD, MPH, of Washington University in St. Louis, said in an interview. “Most concerning is that those on cancer treatment are engaged in a similar level of risky drinking.”

The study was published online in JAMA Network Open.

Drinking alcohol can increase a person’s risk for a variety of cancers, including oral and pharyngeal cancer as well as esophageal, colorectal, liver, and female breast cancers.

Consuming alcohol is also associated with numerous risks among people diagnosed with cancer. In the short term, alcohol consumption can worsen postsurgical outcomes as well as impair cognition and amplify cardiotoxicity in patients undergoing chemotherapy. In the long term, drinking alcohol can elevate a person’s risk of recurrence, secondary tumors, and mortality.

The American Society of Clinical Oncology recently issued a statement reinforcing the need to prioritize alcohol consumption as a key modifiable behavioral factor in the cancer control research agenda.

The current American Cancer Society guidelines indicate that it’s best to avoid or, at least, minimize alcohol consumption. Men should limit their intake to no more than two drinks per day and women should have no more than one drink per day.

Despite this data and guidelines, alcohol drinking patterns among cancer survivors in the United States remain poorly understood.

To explore further, the researchers identified 15,199 adult cancer survivors enrolled in the National Institutes of Health’s All of Us Research Program.

Overall, 78% of the cohort – more than 11,800 individuals – were current drinkers. In a typical day, 24% engaged in binge drinking – consuming six or more drinks on a single occasion – and 38% engaged in hazardous drinking. Using the Alcohol Use Disorders Identification Test–Consumption, the researchers classified hazardous drinking as scores of 4 or higher in men and 3 or higher in women.

Drinking patterns looked similar in the subset of 1,839 patients undergoing cancer treatment. In this group, 76% were current drinkers. Among current drinkers, 12% exceeded moderate drinking levels, 23% reported binge drinking, and 38% engaged in hazardous drinking. In this group, men, Hispanics, people diagnosed with cancer before age 18, and smokers were more likely to engage in risky drinking behaviors.

“We know that many people who are diagnosed with cancer continue to drink alcohol, but this study provides much more detailed information about that,” said Farhad Islami, MD, PhD, senior scientific director for cancer disparity research at the American Cancer Society, Atlanta, who was not involved in the study.

Given the degree of drinking identified in this population, Dr. Cao highlighted the importance of talking to patients about alcohol.

“Our findings highlight an opportunity for enhanced support and intervention concerning risky drinking behaviors” in oncology, Dr. Cao said. “Given the societal norms surrounding alcohol and the general lack of awareness of alcohol’s short- and long-term impact on cancer outcomes, gently educating patients/survivors about potential risks while understanding the cultural and societal contexts of drinking can make a difference.”

Dr. Islami agreed that oncologists should talk to their patients about alcohol, “especially those going through active treatment because alcohol may affect the treatment or may be associated with more complications of the treatment.”

“Many people now know that smoking causes cancer, but unfortunately, many people do not know about the association of alcohol with cancer,” he said.

Outside of an awareness gap, there are numerous risk factors for substance abuse among cancer survivors, Marleen Meyers, MD, director of the cancer survivorship program at NYU Langone Perlmutter Cancer Center, New York, explained.

Alcohol can help some cancer survivors dull feelings of isolation, fear, stress, and poor pain management that may accompany their diagnosis and treatment, said Dr. Meyers, who was not involved in the research. That is why “it is important for patients to be honest with their providers and for providers to ask about substance use in a nonjudgmental way.”

In these conversations, oncologists should educate patients about the safety risks associated with alcohol intake during or after treatment and that there is no established “safe” amount of alcohol. Incorporating a mental health screening and questions about a family history of substance abuse can also help identify patients “most at risk so providers can be proactive,” she said.

The study was supported by a grant from the NIH. Dr. Cao, Dr. Islami, and Dr. Meyers report no relevant financial relationships.

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

The results of a recent study in JAMA Oncology suggest that even short periods of intense, intermittent physical activity are associated with a lower risk for cancer. This activity could be a promising measure for cancer prevention in people who otherwise find it difficult to exercise regularly.

Periods of intense, intermittent physical activity are short phases of strenuous physical exercise that normally last for 1 or 2 minutes, such as a short sprint for the bus or walking up the stairs. In the prospective cohort study conducted in a large group of unathletic adults, researchers investigated a potential dose-effect relationship between intense and daily intermittent physical activity and the cancer incidence rate.

Using data gathered from wearable arm trackers, the researchers analyzed the physical activity of 22,398 people with an average age of 62 years from the UK Biobank. Of these participants, 54.8% were women. After a median follow-up of 6.7 years, corresponding to 149,650 person-years, they determined the general cancer incidence rate in this cohort and the incidence rate of 13 kinds of cancer associated with minimal physical activity (physical-activity related cancers).

Over the study period, 2,356 cancer events occurred, of which 1,084 could be attributed to kinds of cancer associated with minimal physical activity. Nearly all of the intense physical activity (92.3%) was achieved in bursts of up to 1 minute.
 

Four minutes

The daily duration of activity was almost linearly associated with the outcome, wrote Emmanuel Stamatakis, PhD, professor of physical activity, lifestyle, and population health at the University of Sydney. “The dose-effect curve was more vertical, and the extent of the risk reduction for kinds of cancer associated with minimal activity was larger than for the overall cancer incidence rate.”

For example, the lowest dose of intense, intermittent physical activity of up to 1 minute was generally 3.4 minutes per day for cancer in general and 3.7 minutes per day for cancer associated with minimal activity (hazard ratio, 0.83 and 0.72, respectively).

“The results of the study with an average follow-up time of almost 7 years suggest that people with a little less than 4 minutes per day of sporadic intense activity had an overall 17% lower risk of cancer,” wrote Yvonne Wengström, PhD, professor of nursing at Karolinska Institutet in Stockholm, in an accompanying editorial.

For kinds of cancer possibly associated with minimal activity, the researchers found the risk to be reduced by 28% through daily intermittent physical activity. “Even a few minutes of short, intense physical exercise in people with less leisure activity could lower their cancer risk,” wrote Dr. Wengström and colleagues.

Only at the end of 2022 did the data from Dr. Stamatakis and his colleagues suggest a correlation between a little more than 4 minutes of intense physical activity per day and a lower risk for cardiovascular diseases, cancer, and overall mortality in athletes and nonathletes.
 

Wearable arm trackers

The authors of the recent study used an existing cohort’s activity data from an earlier substudy of the UK Biobank that measured acceleration in the wrist. The movement behavior here was recorded over a period of 7 days in more than 90,000 people between 2013 and 2015.

Dr. Wengström and her colleagues rated the arm trackers to be more reliable than the questionnaires that were completed by the subjects. “One strength of the present study is that physical activity was evaluated with the help of wrist acceleration meters, even though nonathletes were defined using the questionnaire data.”

Information about the general lifestyle of healthy living people also had to be included. Dr. Wengström believes that the researchers succeeded in this, because they adjusted the analyses for the following important factors:

• Age.
• Sex.
• Body mass index.
• Level of education.
• Smoking status.
• Alcohol consumption.
• Duration of sleep.
• Fruit and vegetable consumption.
• Medication intake.
• Parental cancer history.

Clinical implications

According to Dr. Wengström, more studies are required to see whether the results of this study can also be transferred to patients who already have a cancer disease. This is because patients with cancer such as premenopausal and postmenopausal women with breast cancer diseases, who have different biologies and hormonal environments, are affected differently by physical activity.

However, physical activity does play a role in patients with cancer “since physical fitness improves muscle strength, cancer-related fatigue, and the survivors’ quality of life,” said Dr. Wengström. However, it is still important to find the correct amount of physical activity for each group of patients and for each patient. Nevertheless, “any physical activity is better than none,” wrote Dr. Wengström and her colleagues.

This article was translated from Medscape’s German edition. A version of this article appeared on Medscape.com.

The results of a recent study in JAMA Oncology suggest that even short periods of intense, intermittent physical activity are associated with a lower risk for cancer. This activity could be a promising measure for cancer prevention in people who otherwise find it difficult to exercise regularly.

Periods of intense, intermittent physical activity are short phases of strenuous physical exercise that normally last for 1 or 2 minutes, such as a short sprint for the bus or walking up the stairs. In the prospective cohort study conducted in a large group of unathletic adults, researchers investigated a potential dose-effect relationship between intense and daily intermittent physical activity and the cancer incidence rate.

Using data gathered from wearable arm trackers, the researchers analyzed the physical activity of 22,398 people with an average age of 62 years from the UK Biobank. Of these participants, 54.8% were women. After a median follow-up of 6.7 years, corresponding to 149,650 person-years, they determined the general cancer incidence rate in this cohort and the incidence rate of 13 kinds of cancer associated with minimal physical activity (physical-activity related cancers).

Over the study period, 2,356 cancer events occurred, of which 1,084 could be attributed to kinds of cancer associated with minimal physical activity. Nearly all of the intense physical activity (92.3%) was achieved in bursts of up to 1 minute.
 

Four minutes

The daily duration of activity was almost linearly associated with the outcome, wrote Emmanuel Stamatakis, PhD, professor of physical activity, lifestyle, and population health at the University of Sydney. “The dose-effect curve was more vertical, and the extent of the risk reduction for kinds of cancer associated with minimal activity was larger than for the overall cancer incidence rate.”

For example, the lowest dose of intense, intermittent physical activity of up to 1 minute was generally 3.4 minutes per day for cancer in general and 3.7 minutes per day for cancer associated with minimal activity (hazard ratio, 0.83 and 0.72, respectively).

“The results of the study with an average follow-up time of almost 7 years suggest that people with a little less than 4 minutes per day of sporadic intense activity had an overall 17% lower risk of cancer,” wrote Yvonne Wengström, PhD, professor of nursing at Karolinska Institutet in Stockholm, in an accompanying editorial.

For kinds of cancer possibly associated with minimal activity, the researchers found the risk to be reduced by 28% through daily intermittent physical activity. “Even a few minutes of short, intense physical exercise in people with less leisure activity could lower their cancer risk,” wrote Dr. Wengström and colleagues.

Only at the end of 2022 did the data from Dr. Stamatakis and his colleagues suggest a correlation between a little more than 4 minutes of intense physical activity per day and a lower risk for cardiovascular diseases, cancer, and overall mortality in athletes and nonathletes.
 

Wearable arm trackers

The authors of the recent study used an existing cohort’s activity data from an earlier substudy of the UK Biobank that measured acceleration in the wrist. The movement behavior here was recorded over a period of 7 days in more than 90,000 people between 2013 and 2015.

Dr. Wengström and her colleagues rated the arm trackers to be more reliable than the questionnaires that were completed by the subjects. “One strength of the present study is that physical activity was evaluated with the help of wrist acceleration meters, even though nonathletes were defined using the questionnaire data.”

Information about the general lifestyle of healthy living people also had to be included. Dr. Wengström believes that the researchers succeeded in this, because they adjusted the analyses for the following important factors:

• Age.
• Sex.
• Body mass index.
• Level of education.
• Smoking status.
• Alcohol consumption.
• Duration of sleep.
• Fruit and vegetable consumption.
• Medication intake.
• Parental cancer history.

Clinical implications

According to Dr. Wengström, more studies are required to see whether the results of this study can also be transferred to patients who already have a cancer disease. This is because patients with cancer such as premenopausal and postmenopausal women with breast cancer diseases, who have different biologies and hormonal environments, are affected differently by physical activity.

However, physical activity does play a role in patients with cancer “since physical fitness improves muscle strength, cancer-related fatigue, and the survivors’ quality of life,” said Dr. Wengström. However, it is still important to find the correct amount of physical activity for each group of patients and for each patient. Nevertheless, “any physical activity is better than none,” wrote Dr. Wengström and her colleagues.

This article was translated from Medscape’s German edition. A version of this article appeared on Medscape.com.

The results of a recent study in JAMA Oncology suggest that even short periods of intense, intermittent physical activity are associated with a lower risk for cancer. This activity could be a promising measure for cancer prevention in people who otherwise find it difficult to exercise regularly.

Periods of intense, intermittent physical activity are short phases of strenuous physical exercise that normally last for 1 or 2 minutes, such as a short sprint for the bus or walking up the stairs. In the prospective cohort study conducted in a large group of unathletic adults, researchers investigated a potential dose-effect relationship between intense and daily intermittent physical activity and the cancer incidence rate.

Using data gathered from wearable arm trackers, the researchers analyzed the physical activity of 22,398 people with an average age of 62 years from the UK Biobank. Of these participants, 54.8% were women. After a median follow-up of 6.7 years, corresponding to 149,650 person-years, they determined the general cancer incidence rate in this cohort and the incidence rate of 13 kinds of cancer associated with minimal physical activity (physical-activity related cancers).

Over the study period, 2,356 cancer events occurred, of which 1,084 could be attributed to kinds of cancer associated with minimal physical activity. Nearly all of the intense physical activity (92.3%) was achieved in bursts of up to 1 minute.
 

Four minutes

The daily duration of activity was almost linearly associated with the outcome, wrote Emmanuel Stamatakis, PhD, professor of physical activity, lifestyle, and population health at the University of Sydney. “The dose-effect curve was more vertical, and the extent of the risk reduction for kinds of cancer associated with minimal activity was larger than for the overall cancer incidence rate.”

For example, the lowest dose of intense, intermittent physical activity of up to 1 minute was generally 3.4 minutes per day for cancer in general and 3.7 minutes per day for cancer associated with minimal activity (hazard ratio, 0.83 and 0.72, respectively).

“The results of the study with an average follow-up time of almost 7 years suggest that people with a little less than 4 minutes per day of sporadic intense activity had an overall 17% lower risk of cancer,” wrote Yvonne Wengström, PhD, professor of nursing at Karolinska Institutet in Stockholm, in an accompanying editorial.

For kinds of cancer possibly associated with minimal activity, the researchers found the risk to be reduced by 28% through daily intermittent physical activity. “Even a few minutes of short, intense physical exercise in people with less leisure activity could lower their cancer risk,” wrote Dr. Wengström and colleagues.

Only at the end of 2022 did the data from Dr. Stamatakis and his colleagues suggest a correlation between a little more than 4 minutes of intense physical activity per day and a lower risk for cardiovascular diseases, cancer, and overall mortality in athletes and nonathletes.
 

Wearable arm trackers

The authors of the recent study used an existing cohort’s activity data from an earlier substudy of the UK Biobank that measured acceleration in the wrist. The movement behavior here was recorded over a period of 7 days in more than 90,000 people between 2013 and 2015.

Dr. Wengström and her colleagues rated the arm trackers to be more reliable than the questionnaires that were completed by the subjects. “One strength of the present study is that physical activity was evaluated with the help of wrist acceleration meters, even though nonathletes were defined using the questionnaire data.”

Information about the general lifestyle of healthy living people also had to be included. Dr. Wengström believes that the researchers succeeded in this, because they adjusted the analyses for the following important factors:

• Age.
• Sex.
• Body mass index.
• Level of education.
• Smoking status.
• Alcohol consumption.
• Duration of sleep.
• Fruit and vegetable consumption.
• Medication intake.
• Parental cancer history.

Clinical implications

According to Dr. Wengström, more studies are required to see whether the results of this study can also be transferred to patients who already have a cancer disease. This is because patients with cancer such as premenopausal and postmenopausal women with breast cancer diseases, who have different biologies and hormonal environments, are affected differently by physical activity.

However, physical activity does play a role in patients with cancer “since physical fitness improves muscle strength, cancer-related fatigue, and the survivors’ quality of life,” said Dr. Wengström. However, it is still important to find the correct amount of physical activity for each group of patients and for each patient. Nevertheless, “any physical activity is better than none,” wrote Dr. Wengström and her colleagues.

This article was translated from Medscape’s German edition. A version of this article appeared on Medscape.com.

People under the age of 50 are becoming more likely to be diagnosed with cancer, according to comprehensive new data.

From 2010 to 2019, the rate of cancer diagnoses rose from 100 to 103 cases per 100,000 people, according to the study, published in JAMA Network Open. The increases were driven by jumps in certain types of cancer and within specific age, racial, and ethnic groups. Researchers analyzed data for more than 560,000 people under age 50 who were diagnosed with cancer during the 9-year period.

Breast cancer remained the most common type of cancer to affect younger people, while the most striking increase was seen in gastrointestinal cancers. The rate of people with GI cancers rose 15%.

Women were more likely to be diagnosed with cancer, whereas the rate of cancer among men under age 50 declined by 5%. When the researchers analyzed the data based on a person’s race or ethnicity, they found that cancer rates were increasing among people who are Asian, Pacific Islander, Hispanic, American Indian, or Alaska Native. The rate of cancer among Black people declined and was steady among White people.

The only age group that saw cancer rates increase was 30- to 39-year-olds. One of the top concerns for younger people with cancer is that there is a greater risk for the cancer to spread.

The cancer rate has been declining among older people, the researchers noted. One doctor told The Washington Post that it’s urgent that the reasons for the increases among young people be understood.

“If we don’t understand what’s causing this risk and we can’t do something to change it, we’re afraid that as time goes on, it’s going to become a bigger and bigger challenge,” said Paul Oberstein, MD, director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center, New York. He was not involved in the study.

It’s unclear why cancer rates are rising among young people, but some possible reasons are obesity, alcohol use, smoking, poor sleep, sedentary lifestyle, and things in the environment like pollution and carcinogens, the Post reported.

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

People under the age of 50 are becoming more likely to be diagnosed with cancer, according to comprehensive new data.

From 2010 to 2019, the rate of cancer diagnoses rose from 100 to 103 cases per 100,000 people, according to the study, published in JAMA Network Open. The increases were driven by jumps in certain types of cancer and within specific age, racial, and ethnic groups. Researchers analyzed data for more than 560,000 people under age 50 who were diagnosed with cancer during the 9-year period.

Breast cancer remained the most common type of cancer to affect younger people, while the most striking increase was seen in gastrointestinal cancers. The rate of people with GI cancers rose 15%.

Women were more likely to be diagnosed with cancer, whereas the rate of cancer among men under age 50 declined by 5%. When the researchers analyzed the data based on a person’s race or ethnicity, they found that cancer rates were increasing among people who are Asian, Pacific Islander, Hispanic, American Indian, or Alaska Native. The rate of cancer among Black people declined and was steady among White people.

The only age group that saw cancer rates increase was 30- to 39-year-olds. One of the top concerns for younger people with cancer is that there is a greater risk for the cancer to spread.

The cancer rate has been declining among older people, the researchers noted. One doctor told The Washington Post that it’s urgent that the reasons for the increases among young people be understood.

“If we don’t understand what’s causing this risk and we can’t do something to change it, we’re afraid that as time goes on, it’s going to become a bigger and bigger challenge,” said Paul Oberstein, MD, director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center, New York. He was not involved in the study.

It’s unclear why cancer rates are rising among young people, but some possible reasons are obesity, alcohol use, smoking, poor sleep, sedentary lifestyle, and things in the environment like pollution and carcinogens, the Post reported.

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

People under the age of 50 are becoming more likely to be diagnosed with cancer, according to comprehensive new data.

From 2010 to 2019, the rate of cancer diagnoses rose from 100 to 103 cases per 100,000 people, according to the study, published in JAMA Network Open. The increases were driven by jumps in certain types of cancer and within specific age, racial, and ethnic groups. Researchers analyzed data for more than 560,000 people under age 50 who were diagnosed with cancer during the 9-year period.

Breast cancer remained the most common type of cancer to affect younger people, while the most striking increase was seen in gastrointestinal cancers. The rate of people with GI cancers rose 15%.

Women were more likely to be diagnosed with cancer, whereas the rate of cancer among men under age 50 declined by 5%. When the researchers analyzed the data based on a person’s race or ethnicity, they found that cancer rates were increasing among people who are Asian, Pacific Islander, Hispanic, American Indian, or Alaska Native. The rate of cancer among Black people declined and was steady among White people.

The only age group that saw cancer rates increase was 30- to 39-year-olds. One of the top concerns for younger people with cancer is that there is a greater risk for the cancer to spread.

The cancer rate has been declining among older people, the researchers noted. One doctor told The Washington Post that it’s urgent that the reasons for the increases among young people be understood.

“If we don’t understand what’s causing this risk and we can’t do something to change it, we’re afraid that as time goes on, it’s going to become a bigger and bigger challenge,” said Paul Oberstein, MD, director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center, New York. He was not involved in the study.

It’s unclear why cancer rates are rising among young people, but some possible reasons are obesity, alcohol use, smoking, poor sleep, sedentary lifestyle, and things in the environment like pollution and carcinogens, the Post reported.

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

For carefully selected patients with colorectal cancer (CRC), a liver transplant may offer long-term survival and potentially even cure unresectable liver metastases.

Findings from a Norwegian review of 61 patients who had liver transplants for unresectable colorectal liver metastases found half of patients were still alive at 5 years, and about one in five appeared to be cured at 10 years.

“It seems likely that there is a small group of patients with unresectable colorectal liver metastases who should be considered for transplant, and long-term survival and possibly cure are achievable in these patients with appropriate selection,” Ryan Ellis, MD, and Michael D’Angelica, MD, wrote in a commentary published alongside the study in JAMA Surgery.

The core question, however, is how to identify patients who will benefit the most from a liver transplant, said Dr. Ellis and Dr. D’Angelica, both surgical oncologists in the Hepatopancreatobiliary Service at Memorial Sloan Kettering Cancer Center, New York. Looking closely at who did well in this analysis can offer clues to appropriate patient selection, the editorialists said.

Three decades ago, the oncology community had largely abandoned liver transplant in this population after studies showed overall 5-year survival of less than 20%. Some patients, however, did better, which prompted the Norwegian investigators to attempt to refine patient selection.

In the current prospective nonrandomized study, 61 patients had liver transplants for unresectable metastases at Oslo University Hospital from 2006 to 2020.

The researchers reported a median overall survival of 60.3 months, with about half of patients (50.4%) alive at 5 years.

Most patients (78.3%) experienced a relapse after liver transplant, with a median time to relapse of 9 months and with most occurring within 2 years of transplant. Median overall survival from time of relapse was 37.1 months, with 5-year survival at nearly 35% in this group and with one patient still alive 156 months after relapse.

The remaining 21.7% of patients (n = 13) did not experience a relapse post-transplant at their last follow-up.

Given the variety of responses to liver transplant, how can experts differentiate patients who will benefit most from those who won’t?

The researchers looked at several factors, including Oslo score and Fong Clinical Risk Score. The Oslo score assesses overall survival among liver transplant patients, while the Fong score predicts recurrence risk for patients with CRC liver metastasis following resection. These scores assign one point for each adverse prognostic factor.

Among the 10 patients who had an Oslo Score of 0, median overall survival was 151.6 months, and the 5-year and 10-year survival rates reached nearly 89%. Among the 27 patients with an Oslo Score of 1, median overall survival was 60.3 months, and 5-year overall survival was 54.7%. No patients with an Oslo score of 4 lived for 5 years.

As for FCRS, median overall survival was 164.9 months among those with a score of 1, 90.5 months among those with a score of 2, 59.9 months for those with a score of 3, 32.8 months for those with a score of 4, and 25.3 months for those with the highest score of 5 (P < .001). Overall, these patients had 5-year overall survival of 100%, 63.9%, 49.4%, 33.3%, and 0%, respectively.

In addition to Oslo and Fong scores, metabolic tumor volume on PET scan (PET-MTV) was also a good prognostic factor for survival. Among the 40 patients with MTV values less than 70 cm³, median 5-year overall survival was nearly 67%, while those with values above 70 cm³ had a median 5-year overall survival of 23.3%.

Additional harbingers of low 5-year survival, in addition to higher Oslo and Fong scores and PET-MTV above 70 cm³, included a tumor size greater than 5.5 cm, progressive disease while receiving chemotherapy, primary tumors in the ascending colon, tumor burden scores of 9 or higher, and nine or more liver lesions.

Overall, the current analysis can help oncologists identify patients who may benefit from a liver transplant.

The findings indicate that “patients with liver-only metastases and favorable pretransplant prognostic scoring [have] long-term survival comparable with conventional indications for liver transplant, thus providing a potential curative treatment option in patients otherwise offered only palliative care,” said investigators led by Svein Dueland, MD, PhD, a member of the Transplant Oncology Research Group at Oslo University Hospital.

Perhaps “the most compelling argument in favor of liver transplant lies in the likely curative potential evidenced by the 13 disease-free patients,” Dr. Ellis and Dr. D’Angelica wrote.

But even some patients who had early recurrences did well following transplant. The investigators noted that early recurrences in this population aren’t as dire as in other settings because they generally manifest as slow growing lung metastases that can be caught early and resected with curative intent.

A major hurdle to broader use of liver transplants in this population is the scarcity of donor grafts. To manage demand, the investigators suggested “extended-criteria donor grafts” – grafts that don’t meet ideal criteria – and the use of the RAPID technique for liver transplant, which opens the door to using one graft for two patients and using living donors with low risk to the donor.

Another challenge will be identifying patients with unresectable colorectal liver metastases who may experience long-term survival following transplant and possibly a cure. “We all will need to keep a sharp eye out for these patients – they might be hard to find!” Dr. Ellis and Dr. D’Angelica wrote.

The study was supported by Oslo University Hospital, the Norwegian Cancer Society, and South-Eastern Norway Regional Health Authority. The investigators and editorialists report no relevant financial relationships.

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

For carefully selected patients with colorectal cancer (CRC), a liver transplant may offer long-term survival and potentially even cure unresectable liver metastases.

Findings from a Norwegian review of 61 patients who had liver transplants for unresectable colorectal liver metastases found half of patients were still alive at 5 years, and about one in five appeared to be cured at 10 years.

“It seems likely that there is a small group of patients with unresectable colorectal liver metastases who should be considered for transplant, and long-term survival and possibly cure are achievable in these patients with appropriate selection,” Ryan Ellis, MD, and Michael D’Angelica, MD, wrote in a commentary published alongside the study in JAMA Surgery.

The core question, however, is how to identify patients who will benefit the most from a liver transplant, said Dr. Ellis and Dr. D’Angelica, both surgical oncologists in the Hepatopancreatobiliary Service at Memorial Sloan Kettering Cancer Center, New York. Looking closely at who did well in this analysis can offer clues to appropriate patient selection, the editorialists said.

Three decades ago, the oncology community had largely abandoned liver transplant in this population after studies showed overall 5-year survival of less than 20%. Some patients, however, did better, which prompted the Norwegian investigators to attempt to refine patient selection.

In the current prospective nonrandomized study, 61 patients had liver transplants for unresectable metastases at Oslo University Hospital from 2006 to 2020.

The researchers reported a median overall survival of 60.3 months, with about half of patients (50.4%) alive at 5 years.

Most patients (78.3%) experienced a relapse after liver transplant, with a median time to relapse of 9 months and with most occurring within 2 years of transplant. Median overall survival from time of relapse was 37.1 months, with 5-year survival at nearly 35% in this group and with one patient still alive 156 months after relapse.

The remaining 21.7% of patients (n = 13) did not experience a relapse post-transplant at their last follow-up.

Given the variety of responses to liver transplant, how can experts differentiate patients who will benefit most from those who won’t?

The researchers looked at several factors, including Oslo score and Fong Clinical Risk Score. The Oslo score assesses overall survival among liver transplant patients, while the Fong score predicts recurrence risk for patients with CRC liver metastasis following resection. These scores assign one point for each adverse prognostic factor.

Among the 10 patients who had an Oslo Score of 0, median overall survival was 151.6 months, and the 5-year and 10-year survival rates reached nearly 89%. Among the 27 patients with an Oslo Score of 1, median overall survival was 60.3 months, and 5-year overall survival was 54.7%. No patients with an Oslo score of 4 lived for 5 years.

As for FCRS, median overall survival was 164.9 months among those with a score of 1, 90.5 months among those with a score of 2, 59.9 months for those with a score of 3, 32.8 months for those with a score of 4, and 25.3 months for those with the highest score of 5 (P < .001). Overall, these patients had 5-year overall survival of 100%, 63.9%, 49.4%, 33.3%, and 0%, respectively.

In addition to Oslo and Fong scores, metabolic tumor volume on PET scan (PET-MTV) was also a good prognostic factor for survival. Among the 40 patients with MTV values less than 70 cm³, median 5-year overall survival was nearly 67%, while those with values above 70 cm³ had a median 5-year overall survival of 23.3%.

Additional harbingers of low 5-year survival, in addition to higher Oslo and Fong scores and PET-MTV above 70 cm³, included a tumor size greater than 5.5 cm, progressive disease while receiving chemotherapy, primary tumors in the ascending colon, tumor burden scores of 9 or higher, and nine or more liver lesions.

Overall, the current analysis can help oncologists identify patients who may benefit from a liver transplant.

The findings indicate that “patients with liver-only metastases and favorable pretransplant prognostic scoring [have] long-term survival comparable with conventional indications for liver transplant, thus providing a potential curative treatment option in patients otherwise offered only palliative care,” said investigators led by Svein Dueland, MD, PhD, a member of the Transplant Oncology Research Group at Oslo University Hospital.

Perhaps “the most compelling argument in favor of liver transplant lies in the likely curative potential evidenced by the 13 disease-free patients,” Dr. Ellis and Dr. D’Angelica wrote.

But even some patients who had early recurrences did well following transplant. The investigators noted that early recurrences in this population aren’t as dire as in other settings because they generally manifest as slow growing lung metastases that can be caught early and resected with curative intent.

A major hurdle to broader use of liver transplants in this population is the scarcity of donor grafts. To manage demand, the investigators suggested “extended-criteria donor grafts” – grafts that don’t meet ideal criteria – and the use of the RAPID technique for liver transplant, which opens the door to using one graft for two patients and using living donors with low risk to the donor.

Another challenge will be identifying patients with unresectable colorectal liver metastases who may experience long-term survival following transplant and possibly a cure. “We all will need to keep a sharp eye out for these patients – they might be hard to find!” Dr. Ellis and Dr. D’Angelica wrote.

The study was supported by Oslo University Hospital, the Norwegian Cancer Society, and South-Eastern Norway Regional Health Authority. The investigators and editorialists report no relevant financial relationships.

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

For carefully selected patients with colorectal cancer (CRC), a liver transplant may offer long-term survival and potentially even cure unresectable liver metastases.

Findings from a Norwegian review of 61 patients who had liver transplants for unresectable colorectal liver metastases found half of patients were still alive at 5 years, and about one in five appeared to be cured at 10 years.

“It seems likely that there is a small group of patients with unresectable colorectal liver metastases who should be considered for transplant, and long-term survival and possibly cure are achievable in these patients with appropriate selection,” Ryan Ellis, MD, and Michael D’Angelica, MD, wrote in a commentary published alongside the study in JAMA Surgery.

The core question, however, is how to identify patients who will benefit the most from a liver transplant, said Dr. Ellis and Dr. D’Angelica, both surgical oncologists in the Hepatopancreatobiliary Service at Memorial Sloan Kettering Cancer Center, New York. Looking closely at who did well in this analysis can offer clues to appropriate patient selection, the editorialists said.

Three decades ago, the oncology community had largely abandoned liver transplant in this population after studies showed overall 5-year survival of less than 20%. Some patients, however, did better, which prompted the Norwegian investigators to attempt to refine patient selection.

In the current prospective nonrandomized study, 61 patients had liver transplants for unresectable metastases at Oslo University Hospital from 2006 to 2020.

The researchers reported a median overall survival of 60.3 months, with about half of patients (50.4%) alive at 5 years.

Most patients (78.3%) experienced a relapse after liver transplant, with a median time to relapse of 9 months and with most occurring within 2 years of transplant. Median overall survival from time of relapse was 37.1 months, with 5-year survival at nearly 35% in this group and with one patient still alive 156 months after relapse.

The remaining 21.7% of patients (n = 13) did not experience a relapse post-transplant at their last follow-up.

Given the variety of responses to liver transplant, how can experts differentiate patients who will benefit most from those who won’t?

The researchers looked at several factors, including Oslo score and Fong Clinical Risk Score. The Oslo score assesses overall survival among liver transplant patients, while the Fong score predicts recurrence risk for patients with CRC liver metastasis following resection. These scores assign one point for each adverse prognostic factor.

Among the 10 patients who had an Oslo Score of 0, median overall survival was 151.6 months, and the 5-year and 10-year survival rates reached nearly 89%. Among the 27 patients with an Oslo Score of 1, median overall survival was 60.3 months, and 5-year overall survival was 54.7%. No patients with an Oslo score of 4 lived for 5 years.

As for FCRS, median overall survival was 164.9 months among those with a score of 1, 90.5 months among those with a score of 2, 59.9 months for those with a score of 3, 32.8 months for those with a score of 4, and 25.3 months for those with the highest score of 5 (P < .001). Overall, these patients had 5-year overall survival of 100%, 63.9%, 49.4%, 33.3%, and 0%, respectively.

In addition to Oslo and Fong scores, metabolic tumor volume on PET scan (PET-MTV) was also a good prognostic factor for survival. Among the 40 patients with MTV values less than 70 cm³, median 5-year overall survival was nearly 67%, while those with values above 70 cm³ had a median 5-year overall survival of 23.3%.

Additional harbingers of low 5-year survival, in addition to higher Oslo and Fong scores and PET-MTV above 70 cm³, included a tumor size greater than 5.5 cm, progressive disease while receiving chemotherapy, primary tumors in the ascending colon, tumor burden scores of 9 or higher, and nine or more liver lesions.

Overall, the current analysis can help oncologists identify patients who may benefit from a liver transplant.

The findings indicate that “patients with liver-only metastases and favorable pretransplant prognostic scoring [have] long-term survival comparable with conventional indications for liver transplant, thus providing a potential curative treatment option in patients otherwise offered only palliative care,” said investigators led by Svein Dueland, MD, PhD, a member of the Transplant Oncology Research Group at Oslo University Hospital.

Perhaps “the most compelling argument in favor of liver transplant lies in the likely curative potential evidenced by the 13 disease-free patients,” Dr. Ellis and Dr. D’Angelica wrote.

But even some patients who had early recurrences did well following transplant. The investigators noted that early recurrences in this population aren’t as dire as in other settings because they generally manifest as slow growing lung metastases that can be caught early and resected with curative intent.

A major hurdle to broader use of liver transplants in this population is the scarcity of donor grafts. To manage demand, the investigators suggested “extended-criteria donor grafts” – grafts that don’t meet ideal criteria – and the use of the RAPID technique for liver transplant, which opens the door to using one graft for two patients and using living donors with low risk to the donor.

Another challenge will be identifying patients with unresectable colorectal liver metastases who may experience long-term survival following transplant and possibly a cure. “We all will need to keep a sharp eye out for these patients – they might be hard to find!” Dr. Ellis and Dr. D’Angelica wrote.

The study was supported by Oslo University Hospital, the Norwegian Cancer Society, and South-Eastern Norway Regional Health Authority. The investigators and editorialists report no relevant financial relationships.

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

Ethylene oxide is a compound used to sterilize more than 20 billion devices sold in the U.S. every year. Although this sterilization process helps keep medical devices – and patients – safe, the odorless, flammable gas may also be harming people who live near sterilization plants and who may inhale the compound, which has been linked to an elevated risk of cancer.

Regulatory agencies are currently feuding over the best way to address the dilemma: preserving patient safety versus protecting public health. Lawmakers are weighing in on the matter, which has been the source of multiple civil lawsuits filed by individuals who say they have suffered health problems as a result of exposure to ethylene oxide.

The Environmental Protection Agency and the U.S. Food and Drug Administration agree that use of the compound should be limited, but they are at odds about how quickly limits should be put in place, according to Axios.

A new commercial standard for ethylene oxide proposed by the EPA in April would impose stricter emission restrictions for sterilization facilities and chemical plants – a move that would cut ethylene oxide emissions by 80%, the EPA estimates.

While the FDA says it “shares concerns about the release of ethylene oxide at unsafe levels into the environment,” the agency cautions that moving too fast to cut emissions would disrupt the medical supply chain, which is already experiencing turbulence. The U.S. has been facing the worst drug supply shortages in a decade in addition to severe medical device shortages.

Currently, other methods of sterilization cannot replace the use of ethylene oxide for many devices. Ethylene oxide is used to sterilize about half of all medical devices in the U.S., the FDA says. Given the country’s reliance on this compound for sterilization, the FDA says it is “equally concerned about the potential impact of shortages of sterilized medical devices that would result from disruptions in commercial sterilizer facility operations.”

In 2019, Illinois temporarily closed a sterilization facility over concern regarding ethylene oxide emissions. The closure caused a shortage of a pediatric breathing tube.

Some lawmakers agree that an Interior-Environment bill would require FDA certification that any action by the EPA would not cause a medical device shortage.

The FDA has been working to identify safe alternatives to ethylene oxide for sterilizing medical supplies as well as strategies to reduce emissions of ethylene oxide by capturing the gas or by turning it into a harmless byproduct. In 2019, the FDA launched a pilot program to incentivize companies to develop new sterilization technologies.

“The FDA remains focused in our commitment to encourage novel ways to sterilize medical devices while reducing adverse impacts on the environment and public health and developing solutions to avoid potential shortages of devices that the American public relies upon,” the agency said.

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

Ethylene oxide is a compound used to sterilize more than 20 billion devices sold in the U.S. every year. Although this sterilization process helps keep medical devices – and patients – safe, the odorless, flammable gas may also be harming people who live near sterilization plants and who may inhale the compound, which has been linked to an elevated risk of cancer.

Regulatory agencies are currently feuding over the best way to address the dilemma: preserving patient safety versus protecting public health. Lawmakers are weighing in on the matter, which has been the source of multiple civil lawsuits filed by individuals who say they have suffered health problems as a result of exposure to ethylene oxide.

The Environmental Protection Agency and the U.S. Food and Drug Administration agree that use of the compound should be limited, but they are at odds about how quickly limits should be put in place, according to Axios.

A new commercial standard for ethylene oxide proposed by the EPA in April would impose stricter emission restrictions for sterilization facilities and chemical plants – a move that would cut ethylene oxide emissions by 80%, the EPA estimates.

While the FDA says it “shares concerns about the release of ethylene oxide at unsafe levels into the environment,” the agency cautions that moving too fast to cut emissions would disrupt the medical supply chain, which is already experiencing turbulence. The U.S. has been facing the worst drug supply shortages in a decade in addition to severe medical device shortages.

Currently, other methods of sterilization cannot replace the use of ethylene oxide for many devices. Ethylene oxide is used to sterilize about half of all medical devices in the U.S., the FDA says. Given the country’s reliance on this compound for sterilization, the FDA says it is “equally concerned about the potential impact of shortages of sterilized medical devices that would result from disruptions in commercial sterilizer facility operations.”

In 2019, Illinois temporarily closed a sterilization facility over concern regarding ethylene oxide emissions. The closure caused a shortage of a pediatric breathing tube.

Some lawmakers agree that an Interior-Environment bill would require FDA certification that any action by the EPA would not cause a medical device shortage.

The FDA has been working to identify safe alternatives to ethylene oxide for sterilizing medical supplies as well as strategies to reduce emissions of ethylene oxide by capturing the gas or by turning it into a harmless byproduct. In 2019, the FDA launched a pilot program to incentivize companies to develop new sterilization technologies.

“The FDA remains focused in our commitment to encourage novel ways to sterilize medical devices while reducing adverse impacts on the environment and public health and developing solutions to avoid potential shortages of devices that the American public relies upon,” the agency said.

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

Ethylene oxide is a compound used to sterilize more than 20 billion devices sold in the U.S. every year. Although this sterilization process helps keep medical devices – and patients – safe, the odorless, flammable gas may also be harming people who live near sterilization plants and who may inhale the compound, which has been linked to an elevated risk of cancer.

Regulatory agencies are currently feuding over the best way to address the dilemma: preserving patient safety versus protecting public health. Lawmakers are weighing in on the matter, which has been the source of multiple civil lawsuits filed by individuals who say they have suffered health problems as a result of exposure to ethylene oxide.

The Environmental Protection Agency and the U.S. Food and Drug Administration agree that use of the compound should be limited, but they are at odds about how quickly limits should be put in place, according to Axios.

A new commercial standard for ethylene oxide proposed by the EPA in April would impose stricter emission restrictions for sterilization facilities and chemical plants – a move that would cut ethylene oxide emissions by 80%, the EPA estimates.

While the FDA says it “shares concerns about the release of ethylene oxide at unsafe levels into the environment,” the agency cautions that moving too fast to cut emissions would disrupt the medical supply chain, which is already experiencing turbulence. The U.S. has been facing the worst drug supply shortages in a decade in addition to severe medical device shortages.

Currently, other methods of sterilization cannot replace the use of ethylene oxide for many devices. Ethylene oxide is used to sterilize about half of all medical devices in the U.S., the FDA says. Given the country’s reliance on this compound for sterilization, the FDA says it is “equally concerned about the potential impact of shortages of sterilized medical devices that would result from disruptions in commercial sterilizer facility operations.”

In 2019, Illinois temporarily closed a sterilization facility over concern regarding ethylene oxide emissions. The closure caused a shortage of a pediatric breathing tube.

Some lawmakers agree that an Interior-Environment bill would require FDA certification that any action by the EPA would not cause a medical device shortage.

The FDA has been working to identify safe alternatives to ethylene oxide for sterilizing medical supplies as well as strategies to reduce emissions of ethylene oxide by capturing the gas or by turning it into a harmless byproduct. In 2019, the FDA launched a pilot program to incentivize companies to develop new sterilization technologies.

“The FDA remains focused in our commitment to encourage novel ways to sterilize medical devices while reducing adverse impacts on the environment and public health and developing solutions to avoid potential shortages of devices that the American public relies upon,” the agency said.

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

Providing access to clinical trials for veteran and active-duty military patients can be a challenge, but many trials are now recruiting patients from those populations. Some trials explicitly recruit patients seeking care at the US Department of Veterans Affairs (VA), US Department of Defense (DoD) Military Health System, and Indian Health Service. The VA Office of Research and Development alone supported > 7260 research projects in 2022, and many more are sponsored by Walter Reed National Medical Center and other major defense and VA facilities. The clinical trials listed below are all open as of July 20, 2023; have at least 1 VA or DoD location recruiting patients; and are focused on treatments for lymphoma, leukemia, and esophageal cancer. For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.

Lymphoma

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin’s Lymphomas

Targeted drug therapies have greatly improved outcomes for patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma. However, single drug therapies have limitations, therefore, the current study is evaluating a novel oral combination of targeted drugs as a way of overcoming these limitations. This study will determine the efficacy of the triple combination therapy, DTRM-555, in patients with R/R CLL or R/R non-Hodgkin’s lymphoma.

ID: NCT04305444

Sponsor: Zhejiang DTRM Biopharma

Locations: 8 locations, including Memphis VA Medical Center

Randomized Phase IIB Trial of Oral Azacytidine Plus Romidepsin Versus Investigator’s Choice in PTCL (PTCL)

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphoma (NHL) originating from mature (or post-thymic or ‘peripheral’) T-lymphocytes and NK cells. They are considered very aggressive and are often resistant to conventional chemotherapy.

This study employs a stratified randomization with equal allocation within strata of patients to receive oral 5-azacytidine (AZA) plus romidepsin (ROMI) versus prespecified investigator choice (ROMI, belinostat, pralatrexate or gemcitabine), for the treatment of relapsed or refractory (R/R) PTCL. The dose and schedule of AZA/ROMI has been determined from a phase I clinical trial of the combination. The primary objective of this study is to estimate the progression-free survival (PFS) among patients receiving the combination compared to single agent of choice.

ID: NCT04747236

Sponsor: Collaborator: University of Virginia; Celgene

Locations: 4 locations, including VA Long Beach Health Care System

Connect® Lymphoma Disease Registry: A US-Based Prospective Observational Cohort Study

This Disease Registry is designed to capture the patient characteristics, practice patterns, and therapeutic strategies evaluated in community and academic centers when treating relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), and R/R follicular lymphoma (FL). The data collected in this Registry will facilitate the evaluation of the current treatment landscape for non-Hodgkin lymphoma (NHL), including the clinical effectiveness, safety. No investigational product or drug will be administered as part of this study. Enrolled patients will receive treatment and evaluations for their disease according to the standard of care and routine clinical practice at each study site. All treatments that patients receive for their disease will be recorded, including any previous lymphoma treatments. Clinical outcomes will be documented as part of an objective clinical assessment. In addition, patient-reported health-related quality of life (HRQoL) outcomes data will be collected from patients using various validated instruments. Social support data will also be collected.

ID: NCT04982471

Sponsor: Celgene

Locations: 60 locations, including VA Central California Health Care System, Harry S. Truman Memorial Veterans’ Hospital, and Brooke Army Medical Center

Obinutuzumab With or Without Umbralisib,Lenalidomide, or Combination Chemotherapy in Treating Patients With Relapsed or Refractory Grade I-IIIa Follicular Lymphoma

This phase II trial studies how well obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy work in treating patients with grade I-IIIa follicular lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with obinutuzumab, may induce changes in the body’s immune system and may interfere with the ability of tumor cells to grow and spread. Umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Chemotherapy drugs, such as cyclophosphamide, doxorubicin, vincristine, prednisone, and bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy will work better in treating patients with grade I-IIIa follicular lymphoma.

ID: NCT03269669

Sponsor: National Cancer Institute (NCI)

Locations: 427 locations, including VA Palo Alto Health Care System

Brentuximab Vedotin and Nivolumab With or Without Ipilimumab in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

This phase I/II trial studies the side effects and best dose of ipilimumab and nivolumab when given together with brentuximab vedotin, and how well they work in treating patients with Hodgkin lymphoma that has returned after a period of improvement (recurrent) or has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body’s immune system attack the cancer and may interfere with the ability of cancer cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30-positive cancer cells in a targeted way and delivers vedotin to kill them. It is not known whether giving brentuximab vedotin and nivolumab with or without ipilimumab may kill more cancer cells.

ID: NCT01896999

Sponsor: National Cancer Institute (NCI)

Locations: 486 locations, including Walter Reed National Military Medical Center

 

 

Leukemia

Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study

This phase III trial compares early treatment with venetoclax and obinutuzumab versus delayed treatment with venetoclax and obinutuzumab in patients with newly diagnosed high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with the venetoclax and obinutuzumab early (before patients have symptoms) may have better outcomes for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma compared to starting treatment with the venetoclax and obinutuzumab after patients show symptoms.

ID: NCT04269902

Sponsor: National Cancer Institute (NCI)

Locations: 545 locations, Tibor Rubin VA Medical Center, Minneapolis VA Medical Center, and Durham VA Medical Center

Testing the Use of Steroids and TyrosineKinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults

This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-cell Engager (‘BiTE’) that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.

ID: NCT04530565

Sponsor: National Cancer Institute (NCI)

Locations: 180 locations, including Walter Reed National Military Medical Center

Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia (ASC2ESCALATE)

This will be a multicenter Phase II open-label study of asciminib in CML-CP patients who have been previously treated with one prior ATP-binding site TKI with discontinuation due to treatment failure, warning or intolerance. (2L patient cohort). In addition, newly diagnosed CML-CP patients who may have received up to 4 weeks of prior TKI are included in a separate 1L patient cohort.

ID: NCT05384587

Sponsor: Novartis

Locations: 26 locations, including VA Puget Sound Health Care System

Connect® Myeloid Disease Registry

This Disease Registry will collect data on patient characteristics, treatment patterns and clinical outcomes. The objective is to describe how patients with myeloid diseases are treated; and to build a knowledge base regarding the effectiveness and safety of first-line and subsequent treatment regimens in both community and academic settings. Enrolled patients will receive treatment and evaluations for their disease according to the standard of care and routine clinical practice at each study site. All treatments that patients receive for their disease will be recorded, including initial treatment and any subsequent therapy. Data on treatment outcomes, including response rates as measured by the treating physician, evidence of progression, survival, and patient-reported outcomes will be collected quarterly on the electronic CRF.

ID: NCT01688011

Sponsor: Celgene

Locations: 240 locations, including VA Central California Health Care System, John D. Dingell VA Medical Center, Manchester VA Medical Center, Dallas VA Medical Center, White River Junction VA Medical Center, and VA Caribbean Healthcare System

Esophageal Cancer

Non-endoscopic Esophageal Sampling to Detect Barrett’s Esophagus and Esophageal Cancer in Veterans

This study seeks to incorporate non-endoscopic detection method (Esocheck/Esoguard) in primary care practice and test whether this screening modality increases the positive predictive value of upper endoscopy and increases the detection of Barrett’s esophagus and esophageal cancer.

Currently, BE is diagnosed only when patients undergo endoscopy with esophagogastroduodenoscopy (EGD). However, due to the high cost of EGD and the lack of a randomized controlled trials supporting its efficacy, endoscopy to screen for BE is not routinely recommended. Current guidelines do recommend sedated EGD in patients with multiple BE risk factors, refractory GERD, or alarm symptoms. This strategy fails to detect BE in patients whose symptoms are well controlled with either over the counter medications or physician prescribed therapies. It also fails to detect BE in asymptomatic subjects who comprise 40% of those that develop EAC. Thus, < 10% of EACs are diagnosed as early stage lesions caught by surveillance of patients with previously detected BE. Ablative nonsurgical therapies that have been developed for preventing cancer in patients with BE with high-grade dysplasia over the past decade will have little impact and the 5-year survival for EACs will remain a dismal 18% unless more effective programs for identifying BE and early EAC are developed.

Esocheck/Esoguard is a FDA approved device designed to sample the distal esophagus and analyze the collected material for presence of two methylated DNA markers. The Specific Aims of this study are:

To determine sensitivity, specificity, positive and negative predictive value of Esocheck/Esoguard performed in routine practice for detecting BE in an at risk Veteran population

To compare the yield of detected BE using EGD alone vs. stepwise molecular diagnostics(Esocheck/Esoguard) and endoscopic screening strategy (EGD) in at risk Veteran population.

ID: NCT05210049

Sponsor: Cleveland VA Medical Research and Education Foundation

Location: Louis Stokes Cleveland VA Medical Center

Progression of Gastroesophageal Reflux Disease and Barrett’s Esophagus and the Creation of a Barrett’s Registry

The purpose of this study is to determine or evaluate the risk factors such as smoking, family history etc. that cause esophageal cancer and to determine the genetic changes that lead to esophageal cancer. The investigators hypothesis is that systematic collection of data on the natural history of GERD and BE patients and risk factors for development of BE in patients with chronic GERD and progression of BE to dysplasia and adenocarcinoma will provide useful information to develop a decision model for risk stratification and risk reduction strategies in these patients.

ID: NCT00574327

Sponsor: Midwest Biomedical Research Foundation

Location: Kansas City VA Medical Center

Providing access to clinical trials for veteran and active-duty military patients can be a challenge, but many trials are now recruiting patients from those populations. Some trials explicitly recruit patients seeking care at the US Department of Veterans Affairs (VA), US Department of Defense (DoD) Military Health System, and Indian Health Service. The VA Office of Research and Development alone supported > 7260 research projects in 2022, and many more are sponsored by Walter Reed National Medical Center and other major defense and VA facilities. The clinical trials listed below are all open as of July 20, 2023; have at least 1 VA or DoD location recruiting patients; and are focused on treatments for lymphoma, leukemia, and esophageal cancer. For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.

Lymphoma

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin’s Lymphomas

Targeted drug therapies have greatly improved outcomes for patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma. However, single drug therapies have limitations, therefore, the current study is evaluating a novel oral combination of targeted drugs as a way of overcoming these limitations. This study will determine the efficacy of the triple combination therapy, DTRM-555, in patients with R/R CLL or R/R non-Hodgkin’s lymphoma.

ID: NCT04305444

Sponsor: Zhejiang DTRM Biopharma

Locations: 8 locations, including Memphis VA Medical Center

Randomized Phase IIB Trial of Oral Azacytidine Plus Romidepsin Versus Investigator’s Choice in PTCL (PTCL)

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphoma (NHL) originating from mature (or post-thymic or ‘peripheral’) T-lymphocytes and NK cells. They are considered very aggressive and are often resistant to conventional chemotherapy.

This study employs a stratified randomization with equal allocation within strata of patients to receive oral 5-azacytidine (AZA) plus romidepsin (ROMI) versus prespecified investigator choice (ROMI, belinostat, pralatrexate or gemcitabine), for the treatment of relapsed or refractory (R/R) PTCL. The dose and schedule of AZA/ROMI has been determined from a phase I clinical trial of the combination. The primary objective of this study is to estimate the progression-free survival (PFS) among patients receiving the combination compared to single agent of choice.

ID: NCT04747236

Sponsor: Collaborator: University of Virginia; Celgene

Locations: 4 locations, including VA Long Beach Health Care System

Connect® Lymphoma Disease Registry: A US-Based Prospective Observational Cohort Study

This Disease Registry is designed to capture the patient characteristics, practice patterns, and therapeutic strategies evaluated in community and academic centers when treating relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), and R/R follicular lymphoma (FL). The data collected in this Registry will facilitate the evaluation of the current treatment landscape for non-Hodgkin lymphoma (NHL), including the clinical effectiveness, safety. No investigational product or drug will be administered as part of this study. Enrolled patients will receive treatment and evaluations for their disease according to the standard of care and routine clinical practice at each study site. All treatments that patients receive for their disease will be recorded, including any previous lymphoma treatments. Clinical outcomes will be documented as part of an objective clinical assessment. In addition, patient-reported health-related quality of life (HRQoL) outcomes data will be collected from patients using various validated instruments. Social support data will also be collected.

ID: NCT04982471

Sponsor: Celgene

Locations: 60 locations, including VA Central California Health Care System, Harry S. Truman Memorial Veterans’ Hospital, and Brooke Army Medical Center

Obinutuzumab With or Without Umbralisib,Lenalidomide, or Combination Chemotherapy in Treating Patients With Relapsed or Refractory Grade I-IIIa Follicular Lymphoma

This phase II trial studies how well obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy work in treating patients with grade I-IIIa follicular lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with obinutuzumab, may induce changes in the body’s immune system and may interfere with the ability of tumor cells to grow and spread. Umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Chemotherapy drugs, such as cyclophosphamide, doxorubicin, vincristine, prednisone, and bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy will work better in treating patients with grade I-IIIa follicular lymphoma.

ID: NCT03269669

Sponsor: National Cancer Institute (NCI)

Locations: 427 locations, including VA Palo Alto Health Care System

Brentuximab Vedotin and Nivolumab With or Without Ipilimumab in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

This phase I/II trial studies the side effects and best dose of ipilimumab and nivolumab when given together with brentuximab vedotin, and how well they work in treating patients with Hodgkin lymphoma that has returned after a period of improvement (recurrent) or has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body’s immune system attack the cancer and may interfere with the ability of cancer cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30-positive cancer cells in a targeted way and delivers vedotin to kill them. It is not known whether giving brentuximab vedotin and nivolumab with or without ipilimumab may kill more cancer cells.

ID: NCT01896999

Sponsor: National Cancer Institute (NCI)

Locations: 486 locations, including Walter Reed National Military Medical Center

 

 

Leukemia

Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study

This phase III trial compares early treatment with venetoclax and obinutuzumab versus delayed treatment with venetoclax and obinutuzumab in patients with newly diagnosed high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with the venetoclax and obinutuzumab early (before patients have symptoms) may have better outcomes for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma compared to starting treatment with the venetoclax and obinutuzumab after patients show symptoms.

ID: NCT04269902

Sponsor: National Cancer Institute (NCI)

Locations: 545 locations, Tibor Rubin VA Medical Center, Minneapolis VA Medical Center, and Durham VA Medical Center

Testing the Use of Steroids and TyrosineKinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults

This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-cell Engager (‘BiTE’) that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.

ID: NCT04530565

Sponsor: National Cancer Institute (NCI)

Locations: 180 locations, including Walter Reed National Military Medical Center

Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia (ASC2ESCALATE)

This will be a multicenter Phase II open-label study of asciminib in CML-CP patients who have been previously treated with one prior ATP-binding site TKI with discontinuation due to treatment failure, warning or intolerance. (2L patient cohort). In addition, newly diagnosed CML-CP patients who may have received up to 4 weeks of prior TKI are included in a separate 1L patient cohort.

ID: NCT05384587

Sponsor: Novartis

Locations: 26 locations, including VA Puget Sound Health Care System

Connect® Myeloid Disease Registry

This Disease Registry will collect data on patient characteristics, treatment patterns and clinical outcomes. The objective is to describe how patients with myeloid diseases are treated; and to build a knowledge base regarding the effectiveness and safety of first-line and subsequent treatment regimens in both community and academic settings. Enrolled patients will receive treatment and evaluations for their disease according to the standard of care and routine clinical practice at each study site. All treatments that patients receive for their disease will be recorded, including initial treatment and any subsequent therapy. Data on treatment outcomes, including response rates as measured by the treating physician, evidence of progression, survival, and patient-reported outcomes will be collected quarterly on the electronic CRF.

ID: NCT01688011

Sponsor: Celgene

Locations: 240 locations, including VA Central California Health Care System, John D. Dingell VA Medical Center, Manchester VA Medical Center, Dallas VA Medical Center, White River Junction VA Medical Center, and VA Caribbean Healthcare System

Esophageal Cancer

Non-endoscopic Esophageal Sampling to Detect Barrett’s Esophagus and Esophageal Cancer in Veterans

This study seeks to incorporate non-endoscopic detection method (Esocheck/Esoguard) in primary care practice and test whether this screening modality increases the positive predictive value of upper endoscopy and increases the detection of Barrett’s esophagus and esophageal cancer.

Currently, BE is diagnosed only when patients undergo endoscopy with esophagogastroduodenoscopy (EGD). However, due to the high cost of EGD and the lack of a randomized controlled trials supporting its efficacy, endoscopy to screen for BE is not routinely recommended. Current guidelines do recommend sedated EGD in patients with multiple BE risk factors, refractory GERD, or alarm symptoms. This strategy fails to detect BE in patients whose symptoms are well controlled with either over the counter medications or physician prescribed therapies. It also fails to detect BE in asymptomatic subjects who comprise 40% of those that develop EAC. Thus, < 10% of EACs are diagnosed as early stage lesions caught by surveillance of patients with previously detected BE. Ablative nonsurgical therapies that have been developed for preventing cancer in patients with BE with high-grade dysplasia over the past decade will have little impact and the 5-year survival for EACs will remain a dismal 18% unless more effective programs for identifying BE and early EAC are developed.

Esocheck/Esoguard is a FDA approved device designed to sample the distal esophagus and analyze the collected material for presence of two methylated DNA markers. The Specific Aims of this study are:

To determine sensitivity, specificity, positive and negative predictive value of Esocheck/Esoguard performed in routine practice for detecting BE in an at risk Veteran population

To compare the yield of detected BE using EGD alone vs. stepwise molecular diagnostics(Esocheck/Esoguard) and endoscopic screening strategy (EGD) in at risk Veteran population.

ID: NCT05210049

Sponsor: Cleveland VA Medical Research and Education Foundation

Location: Louis Stokes Cleveland VA Medical Center

Progression of Gastroesophageal Reflux Disease and Barrett’s Esophagus and the Creation of a Barrett’s Registry

The purpose of this study is to determine or evaluate the risk factors such as smoking, family history etc. that cause esophageal cancer and to determine the genetic changes that lead to esophageal cancer. The investigators hypothesis is that systematic collection of data on the natural history of GERD and BE patients and risk factors for development of BE in patients with chronic GERD and progression of BE to dysplasia and adenocarcinoma will provide useful information to develop a decision model for risk stratification and risk reduction strategies in these patients.

ID: NCT00574327

Sponsor: Midwest Biomedical Research Foundation

Location: Kansas City VA Medical Center

Providing access to clinical trials for veteran and active-duty military patients can be a challenge, but many trials are now recruiting patients from those populations. Some trials explicitly recruit patients seeking care at the US Department of Veterans Affairs (VA), US Department of Defense (DoD) Military Health System, and Indian Health Service. The VA Office of Research and Development alone supported > 7260 research projects in 2022, and many more are sponsored by Walter Reed National Medical Center and other major defense and VA facilities. The clinical trials listed below are all open as of July 20, 2023; have at least 1 VA or DoD location recruiting patients; and are focused on treatments for lymphoma, leukemia, and esophageal cancer. For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.

Lymphoma

Study of a Triple Combination Therapy, DTRM-555, in Patients With R/R CLL or R/R Non-Hodgkin’s Lymphomas

Targeted drug therapies have greatly improved outcomes for patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma. However, single drug therapies have limitations, therefore, the current study is evaluating a novel oral combination of targeted drugs as a way of overcoming these limitations. This study will determine the efficacy of the triple combination therapy, DTRM-555, in patients with R/R CLL or R/R non-Hodgkin’s lymphoma.

ID: NCT04305444

Sponsor: Zhejiang DTRM Biopharma

Locations: 8 locations, including Memphis VA Medical Center

Randomized Phase IIB Trial of Oral Azacytidine Plus Romidepsin Versus Investigator’s Choice in PTCL (PTCL)

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphoma (NHL) originating from mature (or post-thymic or ‘peripheral’) T-lymphocytes and NK cells. They are considered very aggressive and are often resistant to conventional chemotherapy.

This study employs a stratified randomization with equal allocation within strata of patients to receive oral 5-azacytidine (AZA) plus romidepsin (ROMI) versus prespecified investigator choice (ROMI, belinostat, pralatrexate or gemcitabine), for the treatment of relapsed or refractory (R/R) PTCL. The dose and schedule of AZA/ROMI has been determined from a phase I clinical trial of the combination. The primary objective of this study is to estimate the progression-free survival (PFS) among patients receiving the combination compared to single agent of choice.

ID: NCT04747236

Sponsor: Collaborator: University of Virginia; Celgene

Locations: 4 locations, including VA Long Beach Health Care System

Connect® Lymphoma Disease Registry: A US-Based Prospective Observational Cohort Study

This Disease Registry is designed to capture the patient characteristics, practice patterns, and therapeutic strategies evaluated in community and academic centers when treating relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), and R/R follicular lymphoma (FL). The data collected in this Registry will facilitate the evaluation of the current treatment landscape for non-Hodgkin lymphoma (NHL), including the clinical effectiveness, safety. No investigational product or drug will be administered as part of this study. Enrolled patients will receive treatment and evaluations for their disease according to the standard of care and routine clinical practice at each study site. All treatments that patients receive for their disease will be recorded, including any previous lymphoma treatments. Clinical outcomes will be documented as part of an objective clinical assessment. In addition, patient-reported health-related quality of life (HRQoL) outcomes data will be collected from patients using various validated instruments. Social support data will also be collected.

ID: NCT04982471

Sponsor: Celgene

Locations: 60 locations, including VA Central California Health Care System, Harry S. Truman Memorial Veterans’ Hospital, and Brooke Army Medical Center

Obinutuzumab With or Without Umbralisib,Lenalidomide, or Combination Chemotherapy in Treating Patients With Relapsed or Refractory Grade I-IIIa Follicular Lymphoma

This phase II trial studies how well obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy work in treating patients with grade I-IIIa follicular lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with obinutuzumab, may induce changes in the body’s immune system and may interfere with the ability of tumor cells to grow and spread. Umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Chemotherapy drugs, such as cyclophosphamide, doxorubicin, vincristine, prednisone, and bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy will work better in treating patients with grade I-IIIa follicular lymphoma.

ID: NCT03269669

Sponsor: National Cancer Institute (NCI)

Locations: 427 locations, including VA Palo Alto Health Care System

Brentuximab Vedotin and Nivolumab With or Without Ipilimumab in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

This phase I/II trial studies the side effects and best dose of ipilimumab and nivolumab when given together with brentuximab vedotin, and how well they work in treating patients with Hodgkin lymphoma that has returned after a period of improvement (recurrent) or has not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body’s immune system attack the cancer and may interfere with the ability of cancer cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30-positive cancer cells in a targeted way and delivers vedotin to kill them. It is not known whether giving brentuximab vedotin and nivolumab with or without ipilimumab may kill more cancer cells.

ID: NCT01896999

Sponsor: National Cancer Institute (NCI)

Locations: 486 locations, including Walter Reed National Military Medical Center

 

 

Leukemia

Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study

This phase III trial compares early treatment with venetoclax and obinutuzumab versus delayed treatment with venetoclax and obinutuzumab in patients with newly diagnosed high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with the venetoclax and obinutuzumab early (before patients have symptoms) may have better outcomes for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma compared to starting treatment with the venetoclax and obinutuzumab after patients show symptoms.

ID: NCT04269902

Sponsor: National Cancer Institute (NCI)

Locations: 545 locations, Tibor Rubin VA Medical Center, Minneapolis VA Medical Center, and Durham VA Medical Center

Testing the Use of Steroids and TyrosineKinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults

This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-cell Engager (‘BiTE’) that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.

ID: NCT04530565

Sponsor: National Cancer Institute (NCI)

Locations: 180 locations, including Walter Reed National Military Medical Center

Asciminib Monotherapy, With Dose Escalation, for 2nd and 1st Line Chronic Myelogenous Leukemia (ASC2ESCALATE)

This will be a multicenter Phase II open-label study of asciminib in CML-CP patients who have been previously treated with one prior ATP-binding site TKI with discontinuation due to treatment failure, warning or intolerance. (2L patient cohort). In addition, newly diagnosed CML-CP patients who may have received up to 4 weeks of prior TKI are included in a separate 1L patient cohort.

ID: NCT05384587

Sponsor: Novartis

Locations: 26 locations, including VA Puget Sound Health Care System

Connect® Myeloid Disease Registry

This Disease Registry will collect data on patient characteristics, treatment patterns and clinical outcomes. The objective is to describe how patients with myeloid diseases are treated; and to build a knowledge base regarding the effectiveness and safety of first-line and subsequent treatment regimens in both community and academic settings. Enrolled patients will receive treatment and evaluations for their disease according to the standard of care and routine clinical practice at each study site. All treatments that patients receive for their disease will be recorded, including initial treatment and any subsequent therapy. Data on treatment outcomes, including response rates as measured by the treating physician, evidence of progression, survival, and patient-reported outcomes will be collected quarterly on the electronic CRF.

ID: NCT01688011

Sponsor: Celgene

Locations: 240 locations, including VA Central California Health Care System, John D. Dingell VA Medical Center, Manchester VA Medical Center, Dallas VA Medical Center, White River Junction VA Medical Center, and VA Caribbean Healthcare System

Esophageal Cancer

Non-endoscopic Esophageal Sampling to Detect Barrett’s Esophagus and Esophageal Cancer in Veterans

This study seeks to incorporate non-endoscopic detection method (Esocheck/Esoguard) in primary care practice and test whether this screening modality increases the positive predictive value of upper endoscopy and increases the detection of Barrett’s esophagus and esophageal cancer.

Currently, BE is diagnosed only when patients undergo endoscopy with esophagogastroduodenoscopy (EGD). However, due to the high cost of EGD and the lack of a randomized controlled trials supporting its efficacy, endoscopy to screen for BE is not routinely recommended. Current guidelines do recommend sedated EGD in patients with multiple BE risk factors, refractory GERD, or alarm symptoms. This strategy fails to detect BE in patients whose symptoms are well controlled with either over the counter medications or physician prescribed therapies. It also fails to detect BE in asymptomatic subjects who comprise 40% of those that develop EAC. Thus, < 10% of EACs are diagnosed as early stage lesions caught by surveillance of patients with previously detected BE. Ablative nonsurgical therapies that have been developed for preventing cancer in patients with BE with high-grade dysplasia over the past decade will have little impact and the 5-year survival for EACs will remain a dismal 18% unless more effective programs for identifying BE and early EAC are developed.

Esocheck/Esoguard is a FDA approved device designed to sample the distal esophagus and analyze the collected material for presence of two methylated DNA markers. The Specific Aims of this study are:

To determine sensitivity, specificity, positive and negative predictive value of Esocheck/Esoguard performed in routine practice for detecting BE in an at risk Veteran population

To compare the yield of detected BE using EGD alone vs. stepwise molecular diagnostics(Esocheck/Esoguard) and endoscopic screening strategy (EGD) in at risk Veteran population.

ID: NCT05210049

Sponsor: Cleveland VA Medical Research and Education Foundation

Location: Louis Stokes Cleveland VA Medical Center

Progression of Gastroesophageal Reflux Disease and Barrett’s Esophagus and the Creation of a Barrett’s Registry

The purpose of this study is to determine or evaluate the risk factors such as smoking, family history etc. that cause esophageal cancer and to determine the genetic changes that lead to esophageal cancer. The investigators hypothesis is that systematic collection of data on the natural history of GERD and BE patients and risk factors for development of BE in patients with chronic GERD and progression of BE to dysplasia and adenocarcinoma will provide useful information to develop a decision model for risk stratification and risk reduction strategies in these patients.

ID: NCT00574327

Sponsor: Midwest Biomedical Research Foundation

Location: Kansas City VA Medical Center