Patient & Survivor Care

The US Food and Drug Administration (FDA) has used its expedited withdrawal process to rescind its approval of melphalan flufenamide (also called melflufen; Pepaxto, Oncopeptides AB), which it had approved for combined use with dexamethasone to treat some patients with multiple myeloma.

But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.

Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):

“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?

Melphalan Flufenamide is finally completely withdrawn by @US_FDA

But approval by @EMA_News stays.

How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?

Modern day miracle?”
 

EMA: Pepaxti’s Benefits Exceed Its Risks

The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:

“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.

Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.

“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.

The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.

“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
 

Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’

David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.

Liza Simonsson

“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”

Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”

“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
 

FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks

In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.

OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.

In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.

Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:

“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”

“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.

The US Food and Drug Administration (FDA) has used its expedited withdrawal process to rescind its approval of melphalan flufenamide (also called melflufen; Pepaxto, Oncopeptides AB), which it had approved for combined use with dexamethasone to treat some patients with multiple myeloma.

But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.

Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):

“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?

Melphalan Flufenamide is finally completely withdrawn by @US_FDA

But approval by @EMA_News stays.

How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?

Modern day miracle?”
 

EMA: Pepaxti’s Benefits Exceed Its Risks

The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:

“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.

Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.

“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.

The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.

“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
 

Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’

David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.

Liza Simonsson

“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”

Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”

“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
 

FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks

In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.

OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.

In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.

Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:

“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”

“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.

The US Food and Drug Administration (FDA) has used its expedited withdrawal process to rescind its approval of melphalan flufenamide (also called melflufen; Pepaxto, Oncopeptides AB), which it had approved for combined use with dexamethasone to treat some patients with multiple myeloma.

But the European Medicines Agency (EMA) still authorizes the drug’s manufacturer Oncopeptides AB to market the drug, also called Pepaxti, in Europe, Iceland, Lichtenstein, Norway, and the United Kingdom.

Amol Akhade, MBBS, who describes himself as a senior consultant medical and hemato oncologist–bone marrow transplant physician on LinkedIn, raised questions about the inconsistencies between the FDA and EMA’s opinions about these drugs. Dr. Akhad, of Suyog Cancer Clinics in India, posted via the following handle @SuyogCancer on X (Twitter):

“How can one drug and one trial data [have] two diagonally different outcomes from two different drug approval agencies?

Melphalan Flufenamide is finally completely withdrawn by @US_FDA

But approval by @EMA_News stays.

How can be one drug be harmful across one side of Atlantic Ocean and becomes safe and useful on the other side of Atlantic Ocean?

Modern day miracle?”
 

EMA: Pepaxti’s Benefits Exceed Its Risks

The EMA, which could not be reached for comment regarding why the agency was still allowing patients to use the drug, said the following about Pepaxti on its website:

“The European Medicines Agency decided that Pepaxti’s benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.

Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable,” the agency wrote.

“Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pepaxti have been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Pepaxti are continuously monitored. Suspected side effects reported with Pepaxti are carefully evaluated and any necessary action taken to protect patients,” according to the EMA.

The FDA’s final decision, issued on February 23, 2024, follows its warning in 2021 that meflufen plus dexamethasone exposed patients with multiple myeloma to increased risk for death, and its call for withdrawal of the drug in 2022.

“The grounds for withdrawing approval have been met because: (1) the confirmatory study conducted as a condition of accelerated approval did not confirm Pepaxto’s clinical benefit and (2) the available evidence demonstrates that Pepaxto is not shown to be safe or effective under its conditions of use,” Peter Marks, MD, PhD, Director of the FDA Center for Biologics Evaluation and Research, wrote in the final decision document.
 

Oncopeptides AB: Drug ‘Caters to a Large Unmet Need’

David Augustsson, Director of Corporate Affairs, Oncopeptides AB, explained in an interview why he thinks the EMA and FDA’s actions regarding the drug differ from each other.

Liza Simonsson

“The European Medicines Agency had the opinion that the OCEAN study met its primary endpoint by demonstrating superior progression-free survival and it agreed that the potential detriment of overall survival was limited to patients progressing less than 36 months after an autologous stem cell transplant,” he said.“The FDA was not willing to acknowledge the observed clinically relevant differences across patient subgroups in the OCEAN study as confirmed.”

Mr. Augustsson added that this decision will deprive US patients of access to “a drug we believe caters to a large unmet need among elderly multiple myeloma patients with few treatment options left.”

“While we remain confident that we have science on our side we are of course disappointed in the decision [to remove Pepaxto from the US market],” Oncopeptides AB CEO Sofia Heigis said in a statement. “At the same time this is no change to our plans and we will continue to focus all our attention on the commercialization in Europe, progression of our pipeline and rest of world opportunities.”
 

FDA 'Took Swift Action' to Ensure Users of Pepaxto Were Informed of Risks

In February 2021, the FDA used the Accelerated Approval Program to enable certain patients with multiple myeloma to be treated with the peptide conjugated alkylating drug melflufen plus dexamethasone. Under the program, Oncopeptides was required to conduct the phase III randomized, controlled OCEAN clinical trial.

OCEAN enrolled 495 patients with relapsed/refractory multiple myeloma who had 2 to 4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy. Participants in the multinational study received either melflufen plus dexamethasone or pomalidomide plus dexamethasone until disease progression, unacceptable toxicity, or lack of benefit.

In July 2021, the FDA issued an alert that the study results showed increased risk for death in participants treated with melflufen. In October that year, at FDA request, Oncopeptides removed the drug from the US market but continued to provide it to patients already receiving it. In December 2022, the FDA requested that the company withdraw melflufen’s US marketing authorization.

Responding to questions about the timing of the FDA’s most recent decision about Pepaxto and how the decision will affect patient care in the US, the FDA emailed the following statement to this news organization:

“Since the OCEAN trial results for Pepaxto in 2021, the FDA has responded to safety concerns about Pepaxto by issuing a CDER Alert, communicating concerns to Oncopeptides, holding an Oncologic Drugs Advisory Committee meeting in September 2022, and issuing a letter of notice to Oncopeptides in July 2023, proposing to withdraw Pepaxto (NDA 214383). After receiving the notice, Oncopeptides appealed the withdrawal in August 2023. A meeting was held with the Commissioner’s designee, Dr. Peter Marks, Oncopeptides, and others from FDA in October 2023. Dr. Marks reviewed the record and considered the arguments made on appeal and issued a final decision on February 23, 2024. Prior to reaching a decision, the FDA took swift action to ensure those receiving Pepaxto in the post-confirmatory clinical trial were informed of the risks and that no new patients were enrolled in the trial. We also note that it is our understanding that Pepaxto has not been marketed in the U.S. since October 22, 2021.”

“This is the first time FDA has used the amended procedures for withdrawal of accelerated approval that were enacted in 2023, as part of the Food and Drug Omnibus Report Act of 2022 (FDORA),” the agency wrote in a Feb 23 statement. The agency will also remove melflufen from the Approved Drug Products with Therapeutic Equivalence Evaluations, also called the Orange Book.

Cancer patients with behavioral health disorders are significantly less likely to undergo surgical resections, and more likely to experience poor outcomes when they do have surgery, based on data from a new study of nearly 700,000 individuals.

The reason for this association remains unclear, and highlights the need to address existing behavioral health disorders (BHDs), which can be exacerbated after a patient is diagnosed with cancer, wrote Timothy M. Pawlik, MD, of The Ohio State University, Columbus, and colleagues. A cancer diagnosis can cause not only physical stress, but mental, emotional, social, and economic stress that can prompt a new BHD, cause relapse of a previous BHD, or exacerbate a current BHD, the researchers noted.
 

What is Known About BHDs and Cancer?

Although previous studies have shown a possible association between BHDs and increased cancer risk, as well as reduced compliance with care, the effect of BHDs on outcomes in cancer patients undergoing surgical resection has not been examined, wrote Dr. Pawlik and colleagues.

Previous research has focused on the impact of having a preexisting serious mental illness (SMI) such as schizophrenia and bipolar disorder on cancer care.

A 2023 literature review of 27 studies published in the Journal of Medical Imaging and Radiation Sciences showed that patients with preexisting severe mental illness (such as schizophrenia or bipolar disorder) had greater cancer-related mortality. In that study, the researchers also found that patients with severe mental illness were more likely to have metastatic disease at diagnosis, but less likely to receive optimal treatments, than individuals without SMIs.

Many studies also have focused on patients developing mental health problems (including BHDs) after a cancer diagnosis, but the current study is the first known to examine outcomes in those with BHDs before cancer. 
 

Why Was It Important to Conduct This Study?

“BHDs are a diverse set of mental illnesses that affect an individual’s psychosocial wellbeing, potentially resulting in maladaptive behaviors,” Dr. Pawlik said in an interview. BHDs, which include substance abuse, eating disorders, and sleep disorders, are less common than anxiety/depression, but have an estimated prevalence of 1.3%-3.1% among adults in the United States, he said.

What Does the New Study Add?

In the new review by Dr. Pawlik and colleagues, published in the Journal of the American College of Surgeons (Katayama ES. J Am Coll Surg. 2024 Feb 29. doi: 2024. 10.1097/XCS.0000000000000954), BHDs were defined as substance abuse, eating disorders, or sleep disorders, which had not been the focus of previous studies. The researchers reviewed data from 694,836 adult patients with lung, esophageal, gastric, liver, pancreatic, or colorectal cancer between 2018-2021 using the Medicare Standard Analytic files. A total of 46,719 patients (6.7%) had at least one BHD.

Overall, patients with a BHD were significantly less likely than those without a BHD to undergo surgical resection (20.3% vs. 23.4%). Patients with a BHD also had significantly worse long-term postoperative survival than those without BHDs (median 37.1 months vs. 46.6 months) and significantly higher in-hospital costs ($17,432 vs. 16,159, P less than .001 for all).

Among patients who underwent cancer surgery, the odds of any complication were significantly higher for those with a BHD compared to those with no BHD (odds ratio 1.32), as were the odds of a prolonged length of stay (OR 1.67) and 90-day readmission (OR 1.57).

Dr. Pawlik said he was surprised by several of the findings, including that 1 in 15 Medicare beneficiaries had a BHD diagnosis, “with male sex and minority racial status, as well as higher social vulnerability, being associated with a higher prevalence of BHD.”

Also, the independent association of having a BHD with 30%-50% higher odds of a complication, prolonged length of stay, and 90-day readmission was higher than Dr. Pawlik had anticipated.
 

Why Do Patients With BHDs Have Fewer Surgeries and Worse Outcomes?

The reasons for this association were likely multifactorial and may reflect the greater burden of medical comorbidity and chronic illness in many patients with BHDs because of maladaptive lifestyles or poor nutrition status, Dr. Pawlik said.

“Patients with BHDs also likely face barriers to accessing care, which was noted particularly among patients with BHDs who lived in socially vulnerable areas,” he said. BHD patients also were more likely to be treated at low-volume rather than high-volume hospitals, “which undoubtedly contributed in part to worse outcomes in this cohort of patients,” he added.
 

What Can Oncologists Do to Help?

The take-home message for clinicians is that BHDs are linked to worse surgical outcomes and higher health care costs in cancer patients, Dr. Pawlik said in an interview.

“Enhanced accessibility to behavioral healthcare, as well as comprehensive policy reform related to mental health services are needed to improve care of patients with BHDs,” he said. “For example, implementing psychiatry compensation programs may encourage practice in vulnerable areas,” he said.

Other strategies include a following a collaborative care model involving mental health professionals working in tandem with primary care and mid-level practitioners and increasing use and establishment of telehealth systems to improve patient access to BHD services, he said.
 

What Are the Limitations?

The study by Dr. Pawlik and colleagues was limited by several factors, including the lack of data on younger patients and the full range of BHDs, as well as underreporting of BHDs and the high copays for mental health care, the researchers noted. However, the results suggest that concomitant BHDs are associated with worse cancer outcomes and higher in-hospital costs, and illustrate the need to screen for and target these conditions in cancer patients, the researchers concluded.

What Are the Next Steps for Research?

The current study involved Medicare beneficiaries aged 65 years or older, and more research is needed to investigate the impact of BHDs among younger cancer patients in whom the prevalence may be higher and the impact of BHDs may be different, Dr. Pawlik said in an interview. In addition, the analysis of BHDs as a composite of substance abuse, eating disorders, and sleep disorders (because the numbers were too small to break out data for each disorder, separately) prevented investigation of potential differences and unique challenges faced by distinct subpopulations of BHD patients, he said.

“Future studies should examine the individual impact of substance abuse, eating disorders, and sleep disorders on access to surgery, as well as the potential different impact that each one of these different BHDs may have on postoperative outcomes,” Dr. Pawlik suggested.

The study was supported by The Ohio State University College of Medicine Roessler Summer Research Scholarship. The researchers had no financial conflicts to disclose.

Cancer patients with behavioral health disorders are significantly less likely to undergo surgical resections, and more likely to experience poor outcomes when they do have surgery, based on data from a new study of nearly 700,000 individuals.

The reason for this association remains unclear, and highlights the need to address existing behavioral health disorders (BHDs), which can be exacerbated after a patient is diagnosed with cancer, wrote Timothy M. Pawlik, MD, of The Ohio State University, Columbus, and colleagues. A cancer diagnosis can cause not only physical stress, but mental, emotional, social, and economic stress that can prompt a new BHD, cause relapse of a previous BHD, or exacerbate a current BHD, the researchers noted.
 

What is Known About BHDs and Cancer?

Although previous studies have shown a possible association between BHDs and increased cancer risk, as well as reduced compliance with care, the effect of BHDs on outcomes in cancer patients undergoing surgical resection has not been examined, wrote Dr. Pawlik and colleagues.

Previous research has focused on the impact of having a preexisting serious mental illness (SMI) such as schizophrenia and bipolar disorder on cancer care.

A 2023 literature review of 27 studies published in the Journal of Medical Imaging and Radiation Sciences showed that patients with preexisting severe mental illness (such as schizophrenia or bipolar disorder) had greater cancer-related mortality. In that study, the researchers also found that patients with severe mental illness were more likely to have metastatic disease at diagnosis, but less likely to receive optimal treatments, than individuals without SMIs.

Many studies also have focused on patients developing mental health problems (including BHDs) after a cancer diagnosis, but the current study is the first known to examine outcomes in those with BHDs before cancer. 
 

Why Was It Important to Conduct This Study?

“BHDs are a diverse set of mental illnesses that affect an individual’s psychosocial wellbeing, potentially resulting in maladaptive behaviors,” Dr. Pawlik said in an interview. BHDs, which include substance abuse, eating disorders, and sleep disorders, are less common than anxiety/depression, but have an estimated prevalence of 1.3%-3.1% among adults in the United States, he said.

What Does the New Study Add?

In the new review by Dr. Pawlik and colleagues, published in the Journal of the American College of Surgeons (Katayama ES. J Am Coll Surg. 2024 Feb 29. doi: 2024. 10.1097/XCS.0000000000000954), BHDs were defined as substance abuse, eating disorders, or sleep disorders, which had not been the focus of previous studies. The researchers reviewed data from 694,836 adult patients with lung, esophageal, gastric, liver, pancreatic, or colorectal cancer between 2018-2021 using the Medicare Standard Analytic files. A total of 46,719 patients (6.7%) had at least one BHD.

Overall, patients with a BHD were significantly less likely than those without a BHD to undergo surgical resection (20.3% vs. 23.4%). Patients with a BHD also had significantly worse long-term postoperative survival than those without BHDs (median 37.1 months vs. 46.6 months) and significantly higher in-hospital costs ($17,432 vs. 16,159, P less than .001 for all).

Among patients who underwent cancer surgery, the odds of any complication were significantly higher for those with a BHD compared to those with no BHD (odds ratio 1.32), as were the odds of a prolonged length of stay (OR 1.67) and 90-day readmission (OR 1.57).

Dr. Pawlik said he was surprised by several of the findings, including that 1 in 15 Medicare beneficiaries had a BHD diagnosis, “with male sex and minority racial status, as well as higher social vulnerability, being associated with a higher prevalence of BHD.”

Also, the independent association of having a BHD with 30%-50% higher odds of a complication, prolonged length of stay, and 90-day readmission was higher than Dr. Pawlik had anticipated.
 

Why Do Patients With BHDs Have Fewer Surgeries and Worse Outcomes?

The reasons for this association were likely multifactorial and may reflect the greater burden of medical comorbidity and chronic illness in many patients with BHDs because of maladaptive lifestyles or poor nutrition status, Dr. Pawlik said.

“Patients with BHDs also likely face barriers to accessing care, which was noted particularly among patients with BHDs who lived in socially vulnerable areas,” he said. BHD patients also were more likely to be treated at low-volume rather than high-volume hospitals, “which undoubtedly contributed in part to worse outcomes in this cohort of patients,” he added.
 

What Can Oncologists Do to Help?

The take-home message for clinicians is that BHDs are linked to worse surgical outcomes and higher health care costs in cancer patients, Dr. Pawlik said in an interview.

“Enhanced accessibility to behavioral healthcare, as well as comprehensive policy reform related to mental health services are needed to improve care of patients with BHDs,” he said. “For example, implementing psychiatry compensation programs may encourage practice in vulnerable areas,” he said.

Other strategies include a following a collaborative care model involving mental health professionals working in tandem with primary care and mid-level practitioners and increasing use and establishment of telehealth systems to improve patient access to BHD services, he said.
 

What Are the Limitations?

The study by Dr. Pawlik and colleagues was limited by several factors, including the lack of data on younger patients and the full range of BHDs, as well as underreporting of BHDs and the high copays for mental health care, the researchers noted. However, the results suggest that concomitant BHDs are associated with worse cancer outcomes and higher in-hospital costs, and illustrate the need to screen for and target these conditions in cancer patients, the researchers concluded.

What Are the Next Steps for Research?

The current study involved Medicare beneficiaries aged 65 years or older, and more research is needed to investigate the impact of BHDs among younger cancer patients in whom the prevalence may be higher and the impact of BHDs may be different, Dr. Pawlik said in an interview. In addition, the analysis of BHDs as a composite of substance abuse, eating disorders, and sleep disorders (because the numbers were too small to break out data for each disorder, separately) prevented investigation of potential differences and unique challenges faced by distinct subpopulations of BHD patients, he said.

“Future studies should examine the individual impact of substance abuse, eating disorders, and sleep disorders on access to surgery, as well as the potential different impact that each one of these different BHDs may have on postoperative outcomes,” Dr. Pawlik suggested.

The study was supported by The Ohio State University College of Medicine Roessler Summer Research Scholarship. The researchers had no financial conflicts to disclose.

Cancer patients with behavioral health disorders are significantly less likely to undergo surgical resections, and more likely to experience poor outcomes when they do have surgery, based on data from a new study of nearly 700,000 individuals.

The reason for this association remains unclear, and highlights the need to address existing behavioral health disorders (BHDs), which can be exacerbated after a patient is diagnosed with cancer, wrote Timothy M. Pawlik, MD, of The Ohio State University, Columbus, and colleagues. A cancer diagnosis can cause not only physical stress, but mental, emotional, social, and economic stress that can prompt a new BHD, cause relapse of a previous BHD, or exacerbate a current BHD, the researchers noted.
 

What is Known About BHDs and Cancer?

Although previous studies have shown a possible association between BHDs and increased cancer risk, as well as reduced compliance with care, the effect of BHDs on outcomes in cancer patients undergoing surgical resection has not been examined, wrote Dr. Pawlik and colleagues.

Previous research has focused on the impact of having a preexisting serious mental illness (SMI) such as schizophrenia and bipolar disorder on cancer care.

A 2023 literature review of 27 studies published in the Journal of Medical Imaging and Radiation Sciences showed that patients with preexisting severe mental illness (such as schizophrenia or bipolar disorder) had greater cancer-related mortality. In that study, the researchers also found that patients with severe mental illness were more likely to have metastatic disease at diagnosis, but less likely to receive optimal treatments, than individuals without SMIs.

Many studies also have focused on patients developing mental health problems (including BHDs) after a cancer diagnosis, but the current study is the first known to examine outcomes in those with BHDs before cancer. 
 

Why Was It Important to Conduct This Study?

“BHDs are a diverse set of mental illnesses that affect an individual’s psychosocial wellbeing, potentially resulting in maladaptive behaviors,” Dr. Pawlik said in an interview. BHDs, which include substance abuse, eating disorders, and sleep disorders, are less common than anxiety/depression, but have an estimated prevalence of 1.3%-3.1% among adults in the United States, he said.

What Does the New Study Add?

In the new review by Dr. Pawlik and colleagues, published in the Journal of the American College of Surgeons (Katayama ES. J Am Coll Surg. 2024 Feb 29. doi: 2024. 10.1097/XCS.0000000000000954), BHDs were defined as substance abuse, eating disorders, or sleep disorders, which had not been the focus of previous studies. The researchers reviewed data from 694,836 adult patients with lung, esophageal, gastric, liver, pancreatic, or colorectal cancer between 2018-2021 using the Medicare Standard Analytic files. A total of 46,719 patients (6.7%) had at least one BHD.

Overall, patients with a BHD were significantly less likely than those without a BHD to undergo surgical resection (20.3% vs. 23.4%). Patients with a BHD also had significantly worse long-term postoperative survival than those without BHDs (median 37.1 months vs. 46.6 months) and significantly higher in-hospital costs ($17,432 vs. 16,159, P less than .001 for all).

Among patients who underwent cancer surgery, the odds of any complication were significantly higher for those with a BHD compared to those with no BHD (odds ratio 1.32), as were the odds of a prolonged length of stay (OR 1.67) and 90-day readmission (OR 1.57).

Dr. Pawlik said he was surprised by several of the findings, including that 1 in 15 Medicare beneficiaries had a BHD diagnosis, “with male sex and minority racial status, as well as higher social vulnerability, being associated with a higher prevalence of BHD.”

Also, the independent association of having a BHD with 30%-50% higher odds of a complication, prolonged length of stay, and 90-day readmission was higher than Dr. Pawlik had anticipated.
 

Why Do Patients With BHDs Have Fewer Surgeries and Worse Outcomes?

The reasons for this association were likely multifactorial and may reflect the greater burden of medical comorbidity and chronic illness in many patients with BHDs because of maladaptive lifestyles or poor nutrition status, Dr. Pawlik said.

“Patients with BHDs also likely face barriers to accessing care, which was noted particularly among patients with BHDs who lived in socially vulnerable areas,” he said. BHD patients also were more likely to be treated at low-volume rather than high-volume hospitals, “which undoubtedly contributed in part to worse outcomes in this cohort of patients,” he added.
 

What Can Oncologists Do to Help?

The take-home message for clinicians is that BHDs are linked to worse surgical outcomes and higher health care costs in cancer patients, Dr. Pawlik said in an interview.

“Enhanced accessibility to behavioral healthcare, as well as comprehensive policy reform related to mental health services are needed to improve care of patients with BHDs,” he said. “For example, implementing psychiatry compensation programs may encourage practice in vulnerable areas,” he said.

Other strategies include a following a collaborative care model involving mental health professionals working in tandem with primary care and mid-level practitioners and increasing use and establishment of telehealth systems to improve patient access to BHD services, he said.
 

What Are the Limitations?

The study by Dr. Pawlik and colleagues was limited by several factors, including the lack of data on younger patients and the full range of BHDs, as well as underreporting of BHDs and the high copays for mental health care, the researchers noted. However, the results suggest that concomitant BHDs are associated with worse cancer outcomes and higher in-hospital costs, and illustrate the need to screen for and target these conditions in cancer patients, the researchers concluded.

What Are the Next Steps for Research?

The current study involved Medicare beneficiaries aged 65 years or older, and more research is needed to investigate the impact of BHDs among younger cancer patients in whom the prevalence may be higher and the impact of BHDs may be different, Dr. Pawlik said in an interview. In addition, the analysis of BHDs as a composite of substance abuse, eating disorders, and sleep disorders (because the numbers were too small to break out data for each disorder, separately) prevented investigation of potential differences and unique challenges faced by distinct subpopulations of BHD patients, he said.

“Future studies should examine the individual impact of substance abuse, eating disorders, and sleep disorders on access to surgery, as well as the potential different impact that each one of these different BHDs may have on postoperative outcomes,” Dr. Pawlik suggested.

The study was supported by The Ohio State University College of Medicine Roessler Summer Research Scholarship. The researchers had no financial conflicts to disclose.

Several clinical trials in leukemia and lymphoma have started enrolling recently. Maybe one of your patients could benefit from taking part?

Hematological malignancy scheduled for a human leukocyte antigen–mismatched unrelated donor transplant. Adult patients in this situation who are younger than 66 years may be eligible for a randomized, open-label, phase 2 study run by the Center for International Blood and Bone Marrow Transplant Research.

The purpose of the study is to test whether cyclophosphamide, which is given to prevent a dreaded complication of stem cell transplantation called graft-versus-host disease, can be safely reduced without increasing infection or reducing protection. All participants will receive cyclophosphamide on days 3 and 4 post transplant. One group will receive a reduced dose of cyclophosphamide (25 mg/kg per dose), and the other will be given a usual dose (37.5 mg/kg).

Sites in Michigan, Missouri, Oregon, Virginia, and Washington started recruiting for 190 participants in December 2023. Study centers in Florida, Massachusetts, New York, and Wisconsin are also planned. Infection-free survival is the primary endpoint, and overall survival is a secondary measure. Quality of life (QoL) is not recorded. More details at clinicaltrials.gov.

Untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Adults who are newly diagnosed with this type of cancer and have active disease may wish to consider a randomized, open-label, phase 3 trial testing an experimental Bruton tyrosine kinase (BTK) inhibitor, nemtabrutinib (from Merck Sharp & Dohme), against standard-of-care BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence).

BTK inhibitors target B-cell proliferation in B-cell cancers such as CLL/SLL and allow for chemotherapy-free treatment of some hematological malignancies. In this study, until disease progression, unacceptable toxicity, or another reason for discontinuation occurs, participants will take daily oral nemtabrutinib, ibrutinib, or acalabrutinib.

The study opened in December 2023 in Pennsylvania, Washington, Taiwan, Israel, and the United Kingdom seeking 1200 participants. The primary outcomes are objective response rate and progression-free survival. Overall survival is a secondary outcome, and QoL is not measured. More details at clinicaltrials.gov.

Relapsed or refractory leukemia with a KMT2A-gene rearrangement (KMT2A-r). Children aged 1 month to younger than 6 years with this diagnosis may be able to join an open-label, nonrandomized, Children’s Oncology Group phase 2 study to determine the most tolerable and/or effective dose of an experimental oral drug called revumenib when added to chemotherapy.

KMT2A-gene alterations are associated with a poor prognosis in leukemia. These alterations cause blood cells to dedifferentiate and start proliferating uncontrollably as leukemia cells. The expression of the damaged KMT2A gene relies on a protein called menin. Revumenib, from Syndax Pharmaceuticals, blocks menin and prevents expression of KMT2A.

Children in the study will receive two different regimens of revumenib in combination with chemotherapy for up to a year, or until disease progression or unacceptable toxicity, and will then be followed for up to 5 years. Trial centers in 12 US states opened their doors in January 2024 looking for 78 participants. Toxicities and minimal residual disease are the primary outcomes; overall survival is a secondary outcome, and QoL is not assessed. More details at clinicaltrials.gov.

Previously untreated follicular lymphoma or diffuse large B-cell lymphoma. Adults with one of these types of lymphoma may be eligible for one of three open-label, randomized, phase 3 trials testing odronextamab (from Regeneron). This bispecific antibody is designed to ‘lock together’ CD20 on cancer cells with CD3-expressing cancer-killing T cells. It has shown anti-lymphoma activity in heavily pretreated patients.

Late in 2023, three phase 3 trials turned the spotlight on treatment-naive patients and started recruiting 2115 participants to assess odronextamab in this setting. The trial OLYMPIA-1 will compare odronextamab with standard-of-care rituximab (Rituxan) plus chemotherapy in follicular lymphoma. OLYMPIA-2 will test the drug in combination with chemotherapy, also in follicular lymphoma. OLYMPIA-3 will evaluate odronextamab plus chemotherapy against rituximab and chemotherapy in people with large B-cell lymphoma.

All study drugs, including odronextamab, will be administered by intravenous infusion, and participants will be followed for up to 5 years. Research centers across eight US states and Australia, Czechia, France, Italy, Poland, Spain, Turkey, and Thailand are currently accepting participants for the three trials. The primary outcomes are various measures of toxicity and complete response at 30 months in the follicular lymphoma studies and toxicity and progression-free survival in large B-cell lymphoma. All three trials are measuring overall survival and QoL as secondary endpoints.

Previously untreated stage II, III, or IV follicular lymphoma. Adults with this type of cancer may be eligible to participate in a randomized, open-label, phase 3 study testing whether an experimental therapy called epcoritamab (from AbbVie) improves disease response and is tolerable when added to standard therapy. For up to 120 weeks, one group of participants will receive a combination of intravenous rituximab and oral lenalidomide (Revlimid), while a second group will also receive subcutaneous injections of epcoritamab. Some participants may be offered investigators’ choice of chemotherapy as well.

Sites across Iowa, Maryland, Missouri, Ohio, Washington, and Montana started welcoming their 900 participants in February 2024. The primary outcome is complete response at 30 months. Overall survival and QoL are secondary outcomes. More details at clinicaltrials.gov.

Relapsed or refractory mantle cell lymphoma. Adults facing one of these clinical scenarios can join an Academic and Community Cancer Research United open label, phase 2 trial examining the effectiveness of combining tafasitamab (Monjuvi), lenalidomide, and venetoclax (Venclexta) for such patients.

Frontline therapy does not cure mantle cell lymphoma, and continued relapses are common. In this situation, treatments can include acalabrutinib, ibrutinib, stem cell transplantation, venetoclax, lenalidomide, and rituximab.

In this study, participants will take venetoclax and lenalidomide daily and receive intravenous tafasitamab every 2 weeks after an initial ramp-up period as per clinic standards. Participants will be followed for 5 years after entering the trial. The Mayo Clinic in Rochester, Minnesota, began recruiting the planned 100 trial participants in January 2024. The primary outcome is objective response rate; overall survival is a secondary outcome, and QoL will not be tracked. More details at clinicaltrials.gov.

All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

Several clinical trials in leukemia and lymphoma have started enrolling recently. Maybe one of your patients could benefit from taking part?

Hematological malignancy scheduled for a human leukocyte antigen–mismatched unrelated donor transplant. Adult patients in this situation who are younger than 66 years may be eligible for a randomized, open-label, phase 2 study run by the Center for International Blood and Bone Marrow Transplant Research.

The purpose of the study is to test whether cyclophosphamide, which is given to prevent a dreaded complication of stem cell transplantation called graft-versus-host disease, can be safely reduced without increasing infection or reducing protection. All participants will receive cyclophosphamide on days 3 and 4 post transplant. One group will receive a reduced dose of cyclophosphamide (25 mg/kg per dose), and the other will be given a usual dose (37.5 mg/kg).

Sites in Michigan, Missouri, Oregon, Virginia, and Washington started recruiting for 190 participants in December 2023. Study centers in Florida, Massachusetts, New York, and Wisconsin are also planned. Infection-free survival is the primary endpoint, and overall survival is a secondary measure. Quality of life (QoL) is not recorded. More details at clinicaltrials.gov.

Untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Adults who are newly diagnosed with this type of cancer and have active disease may wish to consider a randomized, open-label, phase 3 trial testing an experimental Bruton tyrosine kinase (BTK) inhibitor, nemtabrutinib (from Merck Sharp & Dohme), against standard-of-care BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence).

BTK inhibitors target B-cell proliferation in B-cell cancers such as CLL/SLL and allow for chemotherapy-free treatment of some hematological malignancies. In this study, until disease progression, unacceptable toxicity, or another reason for discontinuation occurs, participants will take daily oral nemtabrutinib, ibrutinib, or acalabrutinib.

The study opened in December 2023 in Pennsylvania, Washington, Taiwan, Israel, and the United Kingdom seeking 1200 participants. The primary outcomes are objective response rate and progression-free survival. Overall survival is a secondary outcome, and QoL is not measured. More details at clinicaltrials.gov.

Relapsed or refractory leukemia with a KMT2A-gene rearrangement (KMT2A-r). Children aged 1 month to younger than 6 years with this diagnosis may be able to join an open-label, nonrandomized, Children’s Oncology Group phase 2 study to determine the most tolerable and/or effective dose of an experimental oral drug called revumenib when added to chemotherapy.

KMT2A-gene alterations are associated with a poor prognosis in leukemia. These alterations cause blood cells to dedifferentiate and start proliferating uncontrollably as leukemia cells. The expression of the damaged KMT2A gene relies on a protein called menin. Revumenib, from Syndax Pharmaceuticals, blocks menin and prevents expression of KMT2A.

Children in the study will receive two different regimens of revumenib in combination with chemotherapy for up to a year, or until disease progression or unacceptable toxicity, and will then be followed for up to 5 years. Trial centers in 12 US states opened their doors in January 2024 looking for 78 participants. Toxicities and minimal residual disease are the primary outcomes; overall survival is a secondary outcome, and QoL is not assessed. More details at clinicaltrials.gov.

Previously untreated follicular lymphoma or diffuse large B-cell lymphoma. Adults with one of these types of lymphoma may be eligible for one of three open-label, randomized, phase 3 trials testing odronextamab (from Regeneron). This bispecific antibody is designed to ‘lock together’ CD20 on cancer cells with CD3-expressing cancer-killing T cells. It has shown anti-lymphoma activity in heavily pretreated patients.

Late in 2023, three phase 3 trials turned the spotlight on treatment-naive patients and started recruiting 2115 participants to assess odronextamab in this setting. The trial OLYMPIA-1 will compare odronextamab with standard-of-care rituximab (Rituxan) plus chemotherapy in follicular lymphoma. OLYMPIA-2 will test the drug in combination with chemotherapy, also in follicular lymphoma. OLYMPIA-3 will evaluate odronextamab plus chemotherapy against rituximab and chemotherapy in people with large B-cell lymphoma.

All study drugs, including odronextamab, will be administered by intravenous infusion, and participants will be followed for up to 5 years. Research centers across eight US states and Australia, Czechia, France, Italy, Poland, Spain, Turkey, and Thailand are currently accepting participants for the three trials. The primary outcomes are various measures of toxicity and complete response at 30 months in the follicular lymphoma studies and toxicity and progression-free survival in large B-cell lymphoma. All three trials are measuring overall survival and QoL as secondary endpoints.

Previously untreated stage II, III, or IV follicular lymphoma. Adults with this type of cancer may be eligible to participate in a randomized, open-label, phase 3 study testing whether an experimental therapy called epcoritamab (from AbbVie) improves disease response and is tolerable when added to standard therapy. For up to 120 weeks, one group of participants will receive a combination of intravenous rituximab and oral lenalidomide (Revlimid), while a second group will also receive subcutaneous injections of epcoritamab. Some participants may be offered investigators’ choice of chemotherapy as well.

Sites across Iowa, Maryland, Missouri, Ohio, Washington, and Montana started welcoming their 900 participants in February 2024. The primary outcome is complete response at 30 months. Overall survival and QoL are secondary outcomes. More details at clinicaltrials.gov.

Relapsed or refractory mantle cell lymphoma. Adults facing one of these clinical scenarios can join an Academic and Community Cancer Research United open label, phase 2 trial examining the effectiveness of combining tafasitamab (Monjuvi), lenalidomide, and venetoclax (Venclexta) for such patients.

Frontline therapy does not cure mantle cell lymphoma, and continued relapses are common. In this situation, treatments can include acalabrutinib, ibrutinib, stem cell transplantation, venetoclax, lenalidomide, and rituximab.

In this study, participants will take venetoclax and lenalidomide daily and receive intravenous tafasitamab every 2 weeks after an initial ramp-up period as per clinic standards. Participants will be followed for 5 years after entering the trial. The Mayo Clinic in Rochester, Minnesota, began recruiting the planned 100 trial participants in January 2024. The primary outcome is objective response rate; overall survival is a secondary outcome, and QoL will not be tracked. More details at clinicaltrials.gov.

All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

Several clinical trials in leukemia and lymphoma have started enrolling recently. Maybe one of your patients could benefit from taking part?

Hematological malignancy scheduled for a human leukocyte antigen–mismatched unrelated donor transplant. Adult patients in this situation who are younger than 66 years may be eligible for a randomized, open-label, phase 2 study run by the Center for International Blood and Bone Marrow Transplant Research.

The purpose of the study is to test whether cyclophosphamide, which is given to prevent a dreaded complication of stem cell transplantation called graft-versus-host disease, can be safely reduced without increasing infection or reducing protection. All participants will receive cyclophosphamide on days 3 and 4 post transplant. One group will receive a reduced dose of cyclophosphamide (25 mg/kg per dose), and the other will be given a usual dose (37.5 mg/kg).

Sites in Michigan, Missouri, Oregon, Virginia, and Washington started recruiting for 190 participants in December 2023. Study centers in Florida, Massachusetts, New York, and Wisconsin are also planned. Infection-free survival is the primary endpoint, and overall survival is a secondary measure. Quality of life (QoL) is not recorded. More details at clinicaltrials.gov.

Untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Adults who are newly diagnosed with this type of cancer and have active disease may wish to consider a randomized, open-label, phase 3 trial testing an experimental Bruton tyrosine kinase (BTK) inhibitor, nemtabrutinib (from Merck Sharp & Dohme), against standard-of-care BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence).

BTK inhibitors target B-cell proliferation in B-cell cancers such as CLL/SLL and allow for chemotherapy-free treatment of some hematological malignancies. In this study, until disease progression, unacceptable toxicity, or another reason for discontinuation occurs, participants will take daily oral nemtabrutinib, ibrutinib, or acalabrutinib.

The study opened in December 2023 in Pennsylvania, Washington, Taiwan, Israel, and the United Kingdom seeking 1200 participants. The primary outcomes are objective response rate and progression-free survival. Overall survival is a secondary outcome, and QoL is not measured. More details at clinicaltrials.gov.

Relapsed or refractory leukemia with a KMT2A-gene rearrangement (KMT2A-r). Children aged 1 month to younger than 6 years with this diagnosis may be able to join an open-label, nonrandomized, Children’s Oncology Group phase 2 study to determine the most tolerable and/or effective dose of an experimental oral drug called revumenib when added to chemotherapy.

KMT2A-gene alterations are associated with a poor prognosis in leukemia. These alterations cause blood cells to dedifferentiate and start proliferating uncontrollably as leukemia cells. The expression of the damaged KMT2A gene relies on a protein called menin. Revumenib, from Syndax Pharmaceuticals, blocks menin and prevents expression of KMT2A.

Children in the study will receive two different regimens of revumenib in combination with chemotherapy for up to a year, or until disease progression or unacceptable toxicity, and will then be followed for up to 5 years. Trial centers in 12 US states opened their doors in January 2024 looking for 78 participants. Toxicities and minimal residual disease are the primary outcomes; overall survival is a secondary outcome, and QoL is not assessed. More details at clinicaltrials.gov.

Previously untreated follicular lymphoma or diffuse large B-cell lymphoma. Adults with one of these types of lymphoma may be eligible for one of three open-label, randomized, phase 3 trials testing odronextamab (from Regeneron). This bispecific antibody is designed to ‘lock together’ CD20 on cancer cells with CD3-expressing cancer-killing T cells. It has shown anti-lymphoma activity in heavily pretreated patients.

Late in 2023, three phase 3 trials turned the spotlight on treatment-naive patients and started recruiting 2115 participants to assess odronextamab in this setting. The trial OLYMPIA-1 will compare odronextamab with standard-of-care rituximab (Rituxan) plus chemotherapy in follicular lymphoma. OLYMPIA-2 will test the drug in combination with chemotherapy, also in follicular lymphoma. OLYMPIA-3 will evaluate odronextamab plus chemotherapy against rituximab and chemotherapy in people with large B-cell lymphoma.

All study drugs, including odronextamab, will be administered by intravenous infusion, and participants will be followed for up to 5 years. Research centers across eight US states and Australia, Czechia, France, Italy, Poland, Spain, Turkey, and Thailand are currently accepting participants for the three trials. The primary outcomes are various measures of toxicity and complete response at 30 months in the follicular lymphoma studies and toxicity and progression-free survival in large B-cell lymphoma. All three trials are measuring overall survival and QoL as secondary endpoints.

Previously untreated stage II, III, or IV follicular lymphoma. Adults with this type of cancer may be eligible to participate in a randomized, open-label, phase 3 study testing whether an experimental therapy called epcoritamab (from AbbVie) improves disease response and is tolerable when added to standard therapy. For up to 120 weeks, one group of participants will receive a combination of intravenous rituximab and oral lenalidomide (Revlimid), while a second group will also receive subcutaneous injections of epcoritamab. Some participants may be offered investigators’ choice of chemotherapy as well.

Sites across Iowa, Maryland, Missouri, Ohio, Washington, and Montana started welcoming their 900 participants in February 2024. The primary outcome is complete response at 30 months. Overall survival and QoL are secondary outcomes. More details at clinicaltrials.gov.

Relapsed or refractory mantle cell lymphoma. Adults facing one of these clinical scenarios can join an Academic and Community Cancer Research United open label, phase 2 trial examining the effectiveness of combining tafasitamab (Monjuvi), lenalidomide, and venetoclax (Venclexta) for such patients.

Frontline therapy does not cure mantle cell lymphoma, and continued relapses are common. In this situation, treatments can include acalabrutinib, ibrutinib, stem cell transplantation, venetoclax, lenalidomide, and rituximab.

In this study, participants will take venetoclax and lenalidomide daily and receive intravenous tafasitamab every 2 weeks after an initial ramp-up period as per clinic standards. Participants will be followed for 5 years after entering the trial. The Mayo Clinic in Rochester, Minnesota, began recruiting the planned 100 trial participants in January 2024. The primary outcome is objective response rate; overall survival is a secondary outcome, and QoL will not be tracked. More details at clinicaltrials.gov.

All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

TOPLINE:

Doxorubicin increases the risk for breast cancer in women with Hodgkin lymphoma, suggesting the need for increased surveillance.

METHODOLOGY:

• Doxorubicin is a mainstay of Hodgkin lymphoma treatment.
• Studies suggest that girls with Hodgkin lymphoma who receive doxorubicin have a higher risk for breast cancer later in life, but it is unclear if women treated as adults face that same risk.
• To find out, investigators reviewed breast cancer incidence in 1964 Dutch women, ages 15-50, who were treated for Hodgkin lymphoma from 1975 to 2008.
• Patients had survived for at least 5 years, and 57% received doxorubicin.

TAKEAWAY:

• Women treated with doxorubicin had a 40% higher risk for breast cancer, and that risk was independent of age of treatment, receipt of chest radiation, and the use of gonadotoxic agents.
• The risk for breast cancer with doxorubicin was dose-dependent, with each 100 mg/m2 dose increment increasing the risk by 18%.
• The findings held whether women were treated years ago or more recently, despite the evolution of treatment strategies for Hodgkin lymphoma.
• After 30 years of follow-up, nearly one in five survivors (20.8%) developed breast cancer. It took 20 years for the elevated risk for breast cancer following treatment with doxorubicin to emerge.

IN PRACTICE:

The study suggests that adolescent and adult women survivors of Hodgkin lymphoma who received doxorubicin have an increased risk for breast cancer, and this risk is independent of age at first Hodgkin lymphoma treatment, receipt of chest radiotherapy, and gonadotoxic treatment, the authors concluded. “Our results have implications for [breast cancer] surveillance guidelines for [Hodgkin lymphoma] survivors and treatment strategies for patients with newly diagnosed” Hodgkin lymphoma.

SOURCE:

The study, led by Suzanne Neppelenbroek of the Netherlands Cancer Institute, Amsterdam, was published February 15 in the Journal of Clinical Oncology. 

LIMITATIONS:

Recruitment ended in 2008 before the advent of newer treatments such as antibody-drug conjugates and immune checkpoint inhibitors.

DISCLOSURES:

The work was funded by the Dutch Cancer Society. Several authors reported ties to Lilly, AbbVie, Amgen, and other companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Doxorubicin increases the risk for breast cancer in women with Hodgkin lymphoma, suggesting the need for increased surveillance.

METHODOLOGY:

• Doxorubicin is a mainstay of Hodgkin lymphoma treatment.
• Studies suggest that girls with Hodgkin lymphoma who receive doxorubicin have a higher risk for breast cancer later in life, but it is unclear if women treated as adults face that same risk.
• To find out, investigators reviewed breast cancer incidence in 1964 Dutch women, ages 15-50, who were treated for Hodgkin lymphoma from 1975 to 2008.
• Patients had survived for at least 5 years, and 57% received doxorubicin.

TAKEAWAY:

• Women treated with doxorubicin had a 40% higher risk for breast cancer, and that risk was independent of age of treatment, receipt of chest radiation, and the use of gonadotoxic agents.
• The risk for breast cancer with doxorubicin was dose-dependent, with each 100 mg/m2 dose increment increasing the risk by 18%.
• The findings held whether women were treated years ago or more recently, despite the evolution of treatment strategies for Hodgkin lymphoma.
• After 30 years of follow-up, nearly one in five survivors (20.8%) developed breast cancer. It took 20 years for the elevated risk for breast cancer following treatment with doxorubicin to emerge.

IN PRACTICE:

The study suggests that adolescent and adult women survivors of Hodgkin lymphoma who received doxorubicin have an increased risk for breast cancer, and this risk is independent of age at first Hodgkin lymphoma treatment, receipt of chest radiotherapy, and gonadotoxic treatment, the authors concluded. “Our results have implications for [breast cancer] surveillance guidelines for [Hodgkin lymphoma] survivors and treatment strategies for patients with newly diagnosed” Hodgkin lymphoma.

SOURCE:

The study, led by Suzanne Neppelenbroek of the Netherlands Cancer Institute, Amsterdam, was published February 15 in the Journal of Clinical Oncology. 

LIMITATIONS:

Recruitment ended in 2008 before the advent of newer treatments such as antibody-drug conjugates and immune checkpoint inhibitors.

DISCLOSURES:

The work was funded by the Dutch Cancer Society. Several authors reported ties to Lilly, AbbVie, Amgen, and other companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Doxorubicin increases the risk for breast cancer in women with Hodgkin lymphoma, suggesting the need for increased surveillance.

METHODOLOGY:

• Doxorubicin is a mainstay of Hodgkin lymphoma treatment.
• Studies suggest that girls with Hodgkin lymphoma who receive doxorubicin have a higher risk for breast cancer later in life, but it is unclear if women treated as adults face that same risk.
• To find out, investigators reviewed breast cancer incidence in 1964 Dutch women, ages 15-50, who were treated for Hodgkin lymphoma from 1975 to 2008.
• Patients had survived for at least 5 years, and 57% received doxorubicin.

TAKEAWAY:

• Women treated with doxorubicin had a 40% higher risk for breast cancer, and that risk was independent of age of treatment, receipt of chest radiation, and the use of gonadotoxic agents.
• The risk for breast cancer with doxorubicin was dose-dependent, with each 100 mg/m2 dose increment increasing the risk by 18%.
• The findings held whether women were treated years ago or more recently, despite the evolution of treatment strategies for Hodgkin lymphoma.
• After 30 years of follow-up, nearly one in five survivors (20.8%) developed breast cancer. It took 20 years for the elevated risk for breast cancer following treatment with doxorubicin to emerge.

IN PRACTICE:

The study suggests that adolescent and adult women survivors of Hodgkin lymphoma who received doxorubicin have an increased risk for breast cancer, and this risk is independent of age at first Hodgkin lymphoma treatment, receipt of chest radiotherapy, and gonadotoxic treatment, the authors concluded. “Our results have implications for [breast cancer] surveillance guidelines for [Hodgkin lymphoma] survivors and treatment strategies for patients with newly diagnosed” Hodgkin lymphoma.

SOURCE:

The study, led by Suzanne Neppelenbroek of the Netherlands Cancer Institute, Amsterdam, was published February 15 in the Journal of Clinical Oncology. 

LIMITATIONS:

Recruitment ended in 2008 before the advent of newer treatments such as antibody-drug conjugates and immune checkpoint inhibitors.

DISCLOSURES:

The work was funded by the Dutch Cancer Society. Several authors reported ties to Lilly, AbbVie, Amgen, and other companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Radiation exposure to the pulmonary veins during radiotherapy (RT) for non–small cell lung cancer (NSCLC) raises the risk for atrial fibrillation (AF), according to new findings.

METHODOLOGY:

• Arrhythmia — with AF being the most common type — affects roughly 11% of patients following lung cancer RT.
• Given RT’s recognized impact on cardiac tissues over time, researchers hypothesized that the dosage affecting pulmonary veins might contribute to the observed increased rates of AF after RT.
• To investigate, researchers looked back at 420 patients with NSCLC (52% women, median age 70) undergoing definitive RT (± chemo) with modern planning techniques at 55 Gy in 20 once-daily fractions over 4 weeks.
• Most patients underwent treatment planning using volumetric modulated arc therapy (50%) or static gantry intensity-modulated RT (20%). Chemotherapy was administered in a minority of cases (33%).
• Pulmonary veins were contoured on planning CT scans, and dose metrics were calculated. The association between pulmonary veins dose and incidence of new AF was evaluated, with AF verified by a cardiologist.

TAKEAWAY:

• Out of the entire cohort, 26 patients (6%) developed AF a median of 13 months after treatment. All cases of AF were grade 3 except for two grade 4 events.
• Radiation dose to the left and right pulmonary veins was significantly associated with incident AF. Dose volumes most strongly associated with AF were ≥ 55 Gy (V55) on the left and ≥ 10 Gy (V10) on the right.
• The risk for AF increased by 2% per percentage point increase in the left pulmonary veins V55 and 1% in the right pulmonary veins V10. The associations were statistically significant after accounting for cardiovascular factors and risk for death risk.
• The area under the curve for prediction of AF events was 0.64 (P = .02) for the left pulmonary veins V55 and 0.61 (P = .03) for the right pulmonary veins V10. The optimal thresholds for predicting AF were 2% and 54%, respectively.

IN PRACTICE:

“The implications of these data are that actively sparing these structures could reduce the incidence of [AF], and where this is not possible, patients identified as being at high risk of AF could undergo active screening during follow-up,” the researchers said, adding that further validation of these findings should take place before implementation.

SOURCE:

The study, with first author Gerard M. Walls, MB, MRCP, Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast, Northern Ireland, was published online on January 4 in Radiotherapy and Oncology .

LIMITATIONS:

This was a single-center, retrospective study with a small number of AF events. The study may have underestimated the relationship between pulmonary vein irradiation and new AF events. The findings needed validation in larger datasets.

DISCLOSURES:

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

A version of this article appeared on Medscape.com.

TOPLINE:

Radiation exposure to the pulmonary veins during radiotherapy (RT) for non–small cell lung cancer (NSCLC) raises the risk for atrial fibrillation (AF), according to new findings.

METHODOLOGY:

• Arrhythmia — with AF being the most common type — affects roughly 11% of patients following lung cancer RT.
• Given RT’s recognized impact on cardiac tissues over time, researchers hypothesized that the dosage affecting pulmonary veins might contribute to the observed increased rates of AF after RT.
• To investigate, researchers looked back at 420 patients with NSCLC (52% women, median age 70) undergoing definitive RT (± chemo) with modern planning techniques at 55 Gy in 20 once-daily fractions over 4 weeks.
• Most patients underwent treatment planning using volumetric modulated arc therapy (50%) or static gantry intensity-modulated RT (20%). Chemotherapy was administered in a minority of cases (33%).
• Pulmonary veins were contoured on planning CT scans, and dose metrics were calculated. The association between pulmonary veins dose and incidence of new AF was evaluated, with AF verified by a cardiologist.

TAKEAWAY:

• Out of the entire cohort, 26 patients (6%) developed AF a median of 13 months after treatment. All cases of AF were grade 3 except for two grade 4 events.
• Radiation dose to the left and right pulmonary veins was significantly associated with incident AF. Dose volumes most strongly associated with AF were ≥ 55 Gy (V55) on the left and ≥ 10 Gy (V10) on the right.
• The risk for AF increased by 2% per percentage point increase in the left pulmonary veins V55 and 1% in the right pulmonary veins V10. The associations were statistically significant after accounting for cardiovascular factors and risk for death risk.
• The area under the curve for prediction of AF events was 0.64 (P = .02) for the left pulmonary veins V55 and 0.61 (P = .03) for the right pulmonary veins V10. The optimal thresholds for predicting AF were 2% and 54%, respectively.

IN PRACTICE:

“The implications of these data are that actively sparing these structures could reduce the incidence of [AF], and where this is not possible, patients identified as being at high risk of AF could undergo active screening during follow-up,” the researchers said, adding that further validation of these findings should take place before implementation.

SOURCE:

The study, with first author Gerard M. Walls, MB, MRCP, Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast, Northern Ireland, was published online on January 4 in Radiotherapy and Oncology .

LIMITATIONS:

This was a single-center, retrospective study with a small number of AF events. The study may have underestimated the relationship between pulmonary vein irradiation and new AF events. The findings needed validation in larger datasets.

DISCLOSURES:

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

A version of this article appeared on Medscape.com.

TOPLINE:

Radiation exposure to the pulmonary veins during radiotherapy (RT) for non–small cell lung cancer (NSCLC) raises the risk for atrial fibrillation (AF), according to new findings.

METHODOLOGY:

• Arrhythmia — with AF being the most common type — affects roughly 11% of patients following lung cancer RT.
• Given RT’s recognized impact on cardiac tissues over time, researchers hypothesized that the dosage affecting pulmonary veins might contribute to the observed increased rates of AF after RT.
• To investigate, researchers looked back at 420 patients with NSCLC (52% women, median age 70) undergoing definitive RT (± chemo) with modern planning techniques at 55 Gy in 20 once-daily fractions over 4 weeks.
• Most patients underwent treatment planning using volumetric modulated arc therapy (50%) or static gantry intensity-modulated RT (20%). Chemotherapy was administered in a minority of cases (33%).
• Pulmonary veins were contoured on planning CT scans, and dose metrics were calculated. The association between pulmonary veins dose and incidence of new AF was evaluated, with AF verified by a cardiologist.

TAKEAWAY:

• Out of the entire cohort, 26 patients (6%) developed AF a median of 13 months after treatment. All cases of AF were grade 3 except for two grade 4 events.
• Radiation dose to the left and right pulmonary veins was significantly associated with incident AF. Dose volumes most strongly associated with AF were ≥ 55 Gy (V55) on the left and ≥ 10 Gy (V10) on the right.
• The risk for AF increased by 2% per percentage point increase in the left pulmonary veins V55 and 1% in the right pulmonary veins V10. The associations were statistically significant after accounting for cardiovascular factors and risk for death risk.
• The area under the curve for prediction of AF events was 0.64 (P = .02) for the left pulmonary veins V55 and 0.61 (P = .03) for the right pulmonary veins V10. The optimal thresholds for predicting AF were 2% and 54%, respectively.

IN PRACTICE:

“The implications of these data are that actively sparing these structures could reduce the incidence of [AF], and where this is not possible, patients identified as being at high risk of AF could undergo active screening during follow-up,” the researchers said, adding that further validation of these findings should take place before implementation.

SOURCE:

The study, with first author Gerard M. Walls, MB, MRCP, Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast, Northern Ireland, was published online on January 4 in Radiotherapy and Oncology .

LIMITATIONS:

This was a single-center, retrospective study with a small number of AF events. The study may have underestimated the relationship between pulmonary vein irradiation and new AF events. The findings needed validation in larger datasets.

DISCLOSURES:

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

A version of this article appeared on Medscape.com.

Food emulsifiers are among the most widespread food additives. A large cohort study highlighted an association between the consumption of certain emulsifiers and an increased risk for certain cancers, particularly breast and prostate cancer.

Ultraprocessed foods constitute a significant part of our diet, representing approximately 30% of energy intake in France.

Large epidemiologic studies have already linked diets rich in ultraprocessed products to an increased risk for cardiovascular diseases, diabetes, obesity, and mortality. Possible explanations for this association include the presence of additives, particularly emulsifiers. These additives are intended to improve the texture and shelf life of foods.

Recent experimental studies have shown that emulsifiers alter the gut microbiota and may lead to low-grade inflammation. Dysbiosis and chronic inflammation not only increase the risk for inflammatory bowel diseases but are also implicated in the etiology of several other chronic pathologies and certain extraintestinal cancers.

The NutriNet-Santé study provided extensive information on the dietary habits of > 100,000 French participants. A new analysis was conducted, examining the possible link between the presence of emulsifiers in the diet and cancer occurrence. Data from 92,000 participants (78.8% women) were utilized. They covered an average follow-up of 6.7 years, during which 2604 cancer cases were diagnosed, including 750 breast cancers, 322 prostate cancers, and 207 colorectal cancers.

In this cohort, the risk for cancer increased with a higher presence in the diet of products containing certain emulsifiers widely used in industrial food in Europe: Carrageenans (E407), mono- and diglycerides of fatty acids (E471), pectins (E440), and sodium carbonate (E500).

Notably, the highest consumption of mono- and diglycerides of fatty acids (E471) was associated with a 15% increase in the risk for all types of cancer, a 24% increase in breast cancer risk, and a 46% increase in prostate cancer risk. The highest consumption of carrageenans (E407) was associated with a 28% increase in breast cancer risk.

In an analysis by menopausal status, the risk for breast cancer before menopause was associated with high consumption of diphosphates (E450; 45% increase), pectins (E440; 55% increase), and sodium bicarbonate (E500; 48% increase). No link was found between emulsifier consumption and colorectal cancer risk. While some associations were observed for other emulsifiers, they did not persist in sensitivity analyses.

The European Food Safety Agency recently evaluated the risks of emulsifiers, however, and found no safety issues or need to limit daily consumption of several of them, notably E471.

It is certain that cancer is multifactorial, and a single factor (here, exposure to emulsifiers) will not significantly increase the risk. However, while not essential to human health, emulsifiers are widely prevalent in the global market. Therefore, if causality is established, the increased risk could translate into a significant number of preventable cancers at the population level. Confirmation of this causal link will need to be obtained through experimental and epidemiological studies.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Food emulsifiers are among the most widespread food additives. A large cohort study highlighted an association between the consumption of certain emulsifiers and an increased risk for certain cancers, particularly breast and prostate cancer.

Ultraprocessed foods constitute a significant part of our diet, representing approximately 30% of energy intake in France.

Large epidemiologic studies have already linked diets rich in ultraprocessed products to an increased risk for cardiovascular diseases, diabetes, obesity, and mortality. Possible explanations for this association include the presence of additives, particularly emulsifiers. These additives are intended to improve the texture and shelf life of foods.

Recent experimental studies have shown that emulsifiers alter the gut microbiota and may lead to low-grade inflammation. Dysbiosis and chronic inflammation not only increase the risk for inflammatory bowel diseases but are also implicated in the etiology of several other chronic pathologies and certain extraintestinal cancers.

The NutriNet-Santé study provided extensive information on the dietary habits of > 100,000 French participants. A new analysis was conducted, examining the possible link between the presence of emulsifiers in the diet and cancer occurrence. Data from 92,000 participants (78.8% women) were utilized. They covered an average follow-up of 6.7 years, during which 2604 cancer cases were diagnosed, including 750 breast cancers, 322 prostate cancers, and 207 colorectal cancers.

In this cohort, the risk for cancer increased with a higher presence in the diet of products containing certain emulsifiers widely used in industrial food in Europe: Carrageenans (E407), mono- and diglycerides of fatty acids (E471), pectins (E440), and sodium carbonate (E500).

Notably, the highest consumption of mono- and diglycerides of fatty acids (E471) was associated with a 15% increase in the risk for all types of cancer, a 24% increase in breast cancer risk, and a 46% increase in prostate cancer risk. The highest consumption of carrageenans (E407) was associated with a 28% increase in breast cancer risk.

In an analysis by menopausal status, the risk for breast cancer before menopause was associated with high consumption of diphosphates (E450; 45% increase), pectins (E440; 55% increase), and sodium bicarbonate (E500; 48% increase). No link was found between emulsifier consumption and colorectal cancer risk. While some associations were observed for other emulsifiers, they did not persist in sensitivity analyses.

The European Food Safety Agency recently evaluated the risks of emulsifiers, however, and found no safety issues or need to limit daily consumption of several of them, notably E471.

It is certain that cancer is multifactorial, and a single factor (here, exposure to emulsifiers) will not significantly increase the risk. However, while not essential to human health, emulsifiers are widely prevalent in the global market. Therefore, if causality is established, the increased risk could translate into a significant number of preventable cancers at the population level. Confirmation of this causal link will need to be obtained through experimental and epidemiological studies.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Food emulsifiers are among the most widespread food additives. A large cohort study highlighted an association between the consumption of certain emulsifiers and an increased risk for certain cancers, particularly breast and prostate cancer.

Ultraprocessed foods constitute a significant part of our diet, representing approximately 30% of energy intake in France.

Large epidemiologic studies have already linked diets rich in ultraprocessed products to an increased risk for cardiovascular diseases, diabetes, obesity, and mortality. Possible explanations for this association include the presence of additives, particularly emulsifiers. These additives are intended to improve the texture and shelf life of foods.

Recent experimental studies have shown that emulsifiers alter the gut microbiota and may lead to low-grade inflammation. Dysbiosis and chronic inflammation not only increase the risk for inflammatory bowel diseases but are also implicated in the etiology of several other chronic pathologies and certain extraintestinal cancers.

The NutriNet-Santé study provided extensive information on the dietary habits of > 100,000 French participants. A new analysis was conducted, examining the possible link between the presence of emulsifiers in the diet and cancer occurrence. Data from 92,000 participants (78.8% women) were utilized. They covered an average follow-up of 6.7 years, during which 2604 cancer cases were diagnosed, including 750 breast cancers, 322 prostate cancers, and 207 colorectal cancers.

In this cohort, the risk for cancer increased with a higher presence in the diet of products containing certain emulsifiers widely used in industrial food in Europe: Carrageenans (E407), mono- and diglycerides of fatty acids (E471), pectins (E440), and sodium carbonate (E500).

Notably, the highest consumption of mono- and diglycerides of fatty acids (E471) was associated with a 15% increase in the risk for all types of cancer, a 24% increase in breast cancer risk, and a 46% increase in prostate cancer risk. The highest consumption of carrageenans (E407) was associated with a 28% increase in breast cancer risk.

In an analysis by menopausal status, the risk for breast cancer before menopause was associated with high consumption of diphosphates (E450; 45% increase), pectins (E440; 55% increase), and sodium bicarbonate (E500; 48% increase). No link was found between emulsifier consumption and colorectal cancer risk. While some associations were observed for other emulsifiers, they did not persist in sensitivity analyses.

The European Food Safety Agency recently evaluated the risks of emulsifiers, however, and found no safety issues or need to limit daily consumption of several of them, notably E471.

It is certain that cancer is multifactorial, and a single factor (here, exposure to emulsifiers) will not significantly increase the risk. However, while not essential to human health, emulsifiers are widely prevalent in the global market. Therefore, if causality is established, the increased risk could translate into a significant number of preventable cancers at the population level. Confirmation of this causal link will need to be obtained through experimental and epidemiological studies.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

One of my abiding interests, part of my daily routine as a cancer physician, is considering whether we should or should not recommend adjuvant therapy for patients who have just had potentially curative resection of their colorectal cancer.

Our group, the QUASAR Group, made a very significant contribution in terms of trials and knowledge in this field. One of the things that we still need to discuss and think about in our wider community is the impact of adjuvant chemotherapy in older patients.

Colorectal cancer is a disease of the elderly, with the median age of presentation around 72. We know that, at presentation, more than 50% of patients are aged 65 or over and one third of patients are 75 or over. It’s a disease predominantly of the elderly. Are we justified in giving combination chemotherapy with oxaliplatin to high-risk resected colorectal cancer patients?

There’s a very nice report of a meta-analysis by Dottorini and colleagues that came out recently in the Journal of Clinical Oncology. It’s an excellent group. They did their meta-analytical work according to a strict, rational protocol. Their statistical analyses were on point, and they collected data from all the relevant trials.

According to the results of their study, it could be concluded that the addition of oxaliplatin to adjuvant therapy for resected high-risk colorectal cancer in older patients — patients older than 70 — doesn’t result in any statistically significant gain in terms of preventing recurrences or saving lives.

When we did our QUASAR trials, initially we were looking at control vs fluoropyrimidine chemotherapy. Although there was an overall impact on survival of the whole trial group (the 5000 patients in our study), when we looked by decile, there was a significant diminution of benefit even to fluoropyrimidine therapy in our trial in patients aged 70 or above. I think this careful meta-analysis must make us question the use of oxaliplatin in elderly patients.

What could the explanation be? Why could the well-known and described benefits of oxaliplatin, particularly for stage III disease, attenuate in older people? It may be to do with reduction in dose intensity. Older people have more side effects; therefore, the chemotherapy isn’t completed as planned. Although, increasingly these days, we tend only to be giving 3 months of treatment.

Is there something biologically in terms of the biology or the somatic mutational landscape of the tumor in older people? I don’t think so. Certainly, in terms of their capacity, in terms of stem cell reserve to be as resistant to the side effects of chemotherapy as younger people, we know that does attenuate with age.

Food for thought: The majority of patients I see in the clinic for the adjuvant treatment are elderly. The majority are coming these days with high-risk stage II or stage III disease. There is a real question mark about whether we should be using oxaliplatin at all.

Clearly, one would say that we need more trials of chemotherapy in older folk to see if the addition of drugs like oxaliplatin to a fluoropyrimidine backbone really does make a difference. I’ve said many times before that we, the medical community recommending adjuvant treatment, need to have better risk stratifiers. We need to have better prognostic markers. We need to have better indices that would allow us to perhaps consider these combination treatments in a more focused group of patients who may have a higher risk for recurrence.

Have a look at the paper and see what you think. I think it’s well done. It’s certainly given me pause for thought about the treatment that we will offer our elderly patients.

Have a think about it. Let me know if there are any comments that you’d like to make. For the time being, over and out.

Dr. Kerr is Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom. He disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, and Roche.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

One of my abiding interests, part of my daily routine as a cancer physician, is considering whether we should or should not recommend adjuvant therapy for patients who have just had potentially curative resection of their colorectal cancer.

Our group, the QUASAR Group, made a very significant contribution in terms of trials and knowledge in this field. One of the things that we still need to discuss and think about in our wider community is the impact of adjuvant chemotherapy in older patients.

Colorectal cancer is a disease of the elderly, with the median age of presentation around 72. We know that, at presentation, more than 50% of patients are aged 65 or over and one third of patients are 75 or over. It’s a disease predominantly of the elderly. Are we justified in giving combination chemotherapy with oxaliplatin to high-risk resected colorectal cancer patients?

There’s a very nice report of a meta-analysis by Dottorini and colleagues that came out recently in the Journal of Clinical Oncology. It’s an excellent group. They did their meta-analytical work according to a strict, rational protocol. Their statistical analyses were on point, and they collected data from all the relevant trials.

According to the results of their study, it could be concluded that the addition of oxaliplatin to adjuvant therapy for resected high-risk colorectal cancer in older patients — patients older than 70 — doesn’t result in any statistically significant gain in terms of preventing recurrences or saving lives.

When we did our QUASAR trials, initially we were looking at control vs fluoropyrimidine chemotherapy. Although there was an overall impact on survival of the whole trial group (the 5000 patients in our study), when we looked by decile, there was a significant diminution of benefit even to fluoropyrimidine therapy in our trial in patients aged 70 or above. I think this careful meta-analysis must make us question the use of oxaliplatin in elderly patients.

What could the explanation be? Why could the well-known and described benefits of oxaliplatin, particularly for stage III disease, attenuate in older people? It may be to do with reduction in dose intensity. Older people have more side effects; therefore, the chemotherapy isn’t completed as planned. Although, increasingly these days, we tend only to be giving 3 months of treatment.

Is there something biologically in terms of the biology or the somatic mutational landscape of the tumor in older people? I don’t think so. Certainly, in terms of their capacity, in terms of stem cell reserve to be as resistant to the side effects of chemotherapy as younger people, we know that does attenuate with age.

Food for thought: The majority of patients I see in the clinic for the adjuvant treatment are elderly. The majority are coming these days with high-risk stage II or stage III disease. There is a real question mark about whether we should be using oxaliplatin at all.

Clearly, one would say that we need more trials of chemotherapy in older folk to see if the addition of drugs like oxaliplatin to a fluoropyrimidine backbone really does make a difference. I’ve said many times before that we, the medical community recommending adjuvant treatment, need to have better risk stratifiers. We need to have better prognostic markers. We need to have better indices that would allow us to perhaps consider these combination treatments in a more focused group of patients who may have a higher risk for recurrence.

Have a look at the paper and see what you think. I think it’s well done. It’s certainly given me pause for thought about the treatment that we will offer our elderly patients.

Have a think about it. Let me know if there are any comments that you’d like to make. For the time being, over and out.

Dr. Kerr is Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom. He disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, and Roche.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

One of my abiding interests, part of my daily routine as a cancer physician, is considering whether we should or should not recommend adjuvant therapy for patients who have just had potentially curative resection of their colorectal cancer.

Our group, the QUASAR Group, made a very significant contribution in terms of trials and knowledge in this field. One of the things that we still need to discuss and think about in our wider community is the impact of adjuvant chemotherapy in older patients.

Colorectal cancer is a disease of the elderly, with the median age of presentation around 72. We know that, at presentation, more than 50% of patients are aged 65 or over and one third of patients are 75 or over. It’s a disease predominantly of the elderly. Are we justified in giving combination chemotherapy with oxaliplatin to high-risk resected colorectal cancer patients?

There’s a very nice report of a meta-analysis by Dottorini and colleagues that came out recently in the Journal of Clinical Oncology. It’s an excellent group. They did their meta-analytical work according to a strict, rational protocol. Their statistical analyses were on point, and they collected data from all the relevant trials.

According to the results of their study, it could be concluded that the addition of oxaliplatin to adjuvant therapy for resected high-risk colorectal cancer in older patients — patients older than 70 — doesn’t result in any statistically significant gain in terms of preventing recurrences or saving lives.

When we did our QUASAR trials, initially we were looking at control vs fluoropyrimidine chemotherapy. Although there was an overall impact on survival of the whole trial group (the 5000 patients in our study), when we looked by decile, there was a significant diminution of benefit even to fluoropyrimidine therapy in our trial in patients aged 70 or above. I think this careful meta-analysis must make us question the use of oxaliplatin in elderly patients.

What could the explanation be? Why could the well-known and described benefits of oxaliplatin, particularly for stage III disease, attenuate in older people? It may be to do with reduction in dose intensity. Older people have more side effects; therefore, the chemotherapy isn’t completed as planned. Although, increasingly these days, we tend only to be giving 3 months of treatment.

Is there something biologically in terms of the biology or the somatic mutational landscape of the tumor in older people? I don’t think so. Certainly, in terms of their capacity, in terms of stem cell reserve to be as resistant to the side effects of chemotherapy as younger people, we know that does attenuate with age.

Food for thought: The majority of patients I see in the clinic for the adjuvant treatment are elderly. The majority are coming these days with high-risk stage II or stage III disease. There is a real question mark about whether we should be using oxaliplatin at all.

Clearly, one would say that we need more trials of chemotherapy in older folk to see if the addition of drugs like oxaliplatin to a fluoropyrimidine backbone really does make a difference. I’ve said many times before that we, the medical community recommending adjuvant treatment, need to have better risk stratifiers. We need to have better prognostic markers. We need to have better indices that would allow us to perhaps consider these combination treatments in a more focused group of patients who may have a higher risk for recurrence.

Have a look at the paper and see what you think. I think it’s well done. It’s certainly given me pause for thought about the treatment that we will offer our elderly patients.

Have a think about it. Let me know if there are any comments that you’d like to make. For the time being, over and out.

Dr. Kerr is Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom. He disclosed ties with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer HealthCare Pharmaceuticals, Genomic Health, Merck Serono, and Roche.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m delighted to talk about a very interesting topic in this commentary. This is an area that we generally don’t discuss, but it’s one that’s obviously very topical, which includes the question of social media.

The paper I’m referring to is entitled, “More Than a Song and Dance”: Exploration of Patient Perspectives and Educational Quality of Gynecologic Cancer Content on TikTok. The paper was published in Gynecologic Oncology in 2023.

The investigators, very interestingly, looked at the most common hashtags for the five most common gynecologic cancers on TikTok. They had a total of 466.7 million views. They looked at 430 of the 500 top posts that were eligible, looked at 11 central themes, did an objective analysis of educational content based on published strategy for looking at this.

What they found, unfortunately but not surprisingly, overall was that the educational quality and reliability were quite poor. They also noticed considerable differences in disparities based on racial background and really emphasized in their analysis not only how common it is for individuals to look at this content on TikTok but also concerns about what it is that the public, patients, and their families are actually seeing.

This, of course, specifically relates to gynecologic cancers, but almost certainly relates to other cancers as well. Clearly, this is a topic that needs to be discussed widely. It’s very complex and very controversial, but when you think about the information that might be provided to our patients and their families going to social media, it’s important that we understand what they’re seeing, what they’re hearing, what they’re viewing, and the impact this might have on their care and outcomes.

I encourage you to read this very interesting paper if you have an interest in this topic. Again, it was recently published in Gynecologic Oncology. I thank you for your attention.

Dr. Markman is professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California; president of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline and AstraZeneca.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m delighted to talk about a very interesting topic in this commentary. This is an area that we generally don’t discuss, but it’s one that’s obviously very topical, which includes the question of social media.

The paper I’m referring to is entitled, “More Than a Song and Dance”: Exploration of Patient Perspectives and Educational Quality of Gynecologic Cancer Content on TikTok. The paper was published in Gynecologic Oncology in 2023.

The investigators, very interestingly, looked at the most common hashtags for the five most common gynecologic cancers on TikTok. They had a total of 466.7 million views. They looked at 430 of the 500 top posts that were eligible, looked at 11 central themes, did an objective analysis of educational content based on published strategy for looking at this.

What they found, unfortunately but not surprisingly, overall was that the educational quality and reliability were quite poor. They also noticed considerable differences in disparities based on racial background and really emphasized in their analysis not only how common it is for individuals to look at this content on TikTok but also concerns about what it is that the public, patients, and their families are actually seeing.

This, of course, specifically relates to gynecologic cancers, but almost certainly relates to other cancers as well. Clearly, this is a topic that needs to be discussed widely. It’s very complex and very controversial, but when you think about the information that might be provided to our patients and their families going to social media, it’s important that we understand what they’re seeing, what they’re hearing, what they’re viewing, and the impact this might have on their care and outcomes.

I encourage you to read this very interesting paper if you have an interest in this topic. Again, it was recently published in Gynecologic Oncology. I thank you for your attention.

Dr. Markman is professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California; president of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline and AstraZeneca.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m delighted to talk about a very interesting topic in this commentary. This is an area that we generally don’t discuss, but it’s one that’s obviously very topical, which includes the question of social media.

The paper I’m referring to is entitled, “More Than a Song and Dance”: Exploration of Patient Perspectives and Educational Quality of Gynecologic Cancer Content on TikTok. The paper was published in Gynecologic Oncology in 2023.

The investigators, very interestingly, looked at the most common hashtags for the five most common gynecologic cancers on TikTok. They had a total of 466.7 million views. They looked at 430 of the 500 top posts that were eligible, looked at 11 central themes, did an objective analysis of educational content based on published strategy for looking at this.

What they found, unfortunately but not surprisingly, overall was that the educational quality and reliability were quite poor. They also noticed considerable differences in disparities based on racial background and really emphasized in their analysis not only how common it is for individuals to look at this content on TikTok but also concerns about what it is that the public, patients, and their families are actually seeing.

This, of course, specifically relates to gynecologic cancers, but almost certainly relates to other cancers as well. Clearly, this is a topic that needs to be discussed widely. It’s very complex and very controversial, but when you think about the information that might be provided to our patients and their families going to social media, it’s important that we understand what they’re seeing, what they’re hearing, what they’re viewing, and the impact this might have on their care and outcomes.

I encourage you to read this very interesting paper if you have an interest in this topic. Again, it was recently published in Gynecologic Oncology. I thank you for your attention.

Dr. Markman is professor, Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, California; president of Medicine & Science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline and AstraZeneca.

A version of this article appeared on Medscape.com.

Communicating bad news to patients is one of the most stressful and challenging clinical tasks for any physician, regardless of his or her specialty. Delivering bad news to a patient or their close relative is demanding because the information provided during the dialogue can substantially alter the person’s perspective on life. This task is more frequent for physicians caring for oncology patients and can also affect the physician’s emotional state.

The manner in which bad news is communicated plays a significant role in the psychological burden on the patient, and various communication techniques and guidelines have been developed to enable physicians to perform this difficult task effectively.

Revealing bad news in person whenever possible, to address the emotional responses of patients or relatives, is part of the prevailing expert recommendations. However, it has been acknowledged that in certain situations, communicating bad news over the phone is more feasible.

Since the beginning of the COVID-19 pandemic, the disclosure of bad news over the phone has become a necessary substitute for in-person visits and an integral part of clinical practice worldwide. It remains to be clarified what the real psychological impact on patients and their closest relatives is when delivering bad news over the phone compared with delivering it in person.

Right and Wrong Ways

The most popular guideline for communicating bad news is SPIKES, a six-phase protocol with a special application for cancer patients. It is used in various countries (eg, the United States, France, and Germany) as a guide for this sensitive practice and for training in communication skills in this context. The SPIKES acronym refers to the following six recommended steps for delivering bad news:

• Setting: Set up the conversation.
• Perception: Assess the patient’s perception.
• Invitation: Ask the patient what he or she would like to know.
• Knowledge: Provide the patient with knowledge and information, breaking it down into small parts.
• Emotions: Acknowledge and empathetically address the patient’s emotions.
• Strategy and Summary: Summarize and define a medical action plan.

The lesson from SPIKES is that when a person experiences strong emotions, it is difficult to continue discussing anything, and they will struggle to hear anything. Allowing for silence is fundamental. In addition, empathy allows the patient to express his or her feelings and concerns, as well as provide support. The aim is not to argue but to allow the expression of emotions without criticism. However, these recommendations are primarily based on expert opinion and less on empirical evidence, due to the difficulty of studies in assessing patient outcomes in various phases of these protocols.

A recent study analyzed the differences in psychological distress between patients who received bad news over the phone vs those who received it in person. The study was a systematic review and meta-analysis.

The investigators examined 5944 studies, including 11 qualitative analysis studies, nine meta-analyses, and four randomized controlled trials.

In a set of studies ranging from moderate to good quality, no difference in psychological distress was found when bad news was disclosed over the phone compared with in person, regarding anxiety, depression, and posttraumatic stress disorder.

There was no average difference in patient satisfaction levels when bad news was delivered over the phone compared with in person. The risk for dissatisfaction was similar between groups.

Clinical Practice Guidelines

The demand for telemedicine, including the disclosure of bad news, is growing despite the limited knowledge of potential adverse effects. The results of existing studies suggest that the mode of disclosure may play a secondary role, and the manner in which bad news is communicated may be more important.

Therefore, it is paramount to prepare patients or their families for the possibility of receiving bad news well in advance and, during the conversation, to ensure first and foremost that they are in an appropriate environment. The structure and content of the conversation may be relevant, and adhering to dedicated communication strategies can be a wise choice for the physician and the interlocutor.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Communicating bad news to patients is one of the most stressful and challenging clinical tasks for any physician, regardless of his or her specialty. Delivering bad news to a patient or their close relative is demanding because the information provided during the dialogue can substantially alter the person’s perspective on life. This task is more frequent for physicians caring for oncology patients and can also affect the physician’s emotional state.

The manner in which bad news is communicated plays a significant role in the psychological burden on the patient, and various communication techniques and guidelines have been developed to enable physicians to perform this difficult task effectively.

Revealing bad news in person whenever possible, to address the emotional responses of patients or relatives, is part of the prevailing expert recommendations. However, it has been acknowledged that in certain situations, communicating bad news over the phone is more feasible.

Since the beginning of the COVID-19 pandemic, the disclosure of bad news over the phone has become a necessary substitute for in-person visits and an integral part of clinical practice worldwide. It remains to be clarified what the real psychological impact on patients and their closest relatives is when delivering bad news over the phone compared with delivering it in person.

Right and Wrong Ways

The most popular guideline for communicating bad news is SPIKES, a six-phase protocol with a special application for cancer patients. It is used in various countries (eg, the United States, France, and Germany) as a guide for this sensitive practice and for training in communication skills in this context. The SPIKES acronym refers to the following six recommended steps for delivering bad news:

• Setting: Set up the conversation.
• Perception: Assess the patient’s perception.
• Invitation: Ask the patient what he or she would like to know.
• Knowledge: Provide the patient with knowledge and information, breaking it down into small parts.
• Emotions: Acknowledge and empathetically address the patient’s emotions.
• Strategy and Summary: Summarize and define a medical action plan.

The lesson from SPIKES is that when a person experiences strong emotions, it is difficult to continue discussing anything, and they will struggle to hear anything. Allowing for silence is fundamental. In addition, empathy allows the patient to express his or her feelings and concerns, as well as provide support. The aim is not to argue but to allow the expression of emotions without criticism. However, these recommendations are primarily based on expert opinion and less on empirical evidence, due to the difficulty of studies in assessing patient outcomes in various phases of these protocols.

A recent study analyzed the differences in psychological distress between patients who received bad news over the phone vs those who received it in person. The study was a systematic review and meta-analysis.

The investigators examined 5944 studies, including 11 qualitative analysis studies, nine meta-analyses, and four randomized controlled trials.

In a set of studies ranging from moderate to good quality, no difference in psychological distress was found when bad news was disclosed over the phone compared with in person, regarding anxiety, depression, and posttraumatic stress disorder.

There was no average difference in patient satisfaction levels when bad news was delivered over the phone compared with in person. The risk for dissatisfaction was similar between groups.

Clinical Practice Guidelines

The demand for telemedicine, including the disclosure of bad news, is growing despite the limited knowledge of potential adverse effects. The results of existing studies suggest that the mode of disclosure may play a secondary role, and the manner in which bad news is communicated may be more important.

Therefore, it is paramount to prepare patients or their families for the possibility of receiving bad news well in advance and, during the conversation, to ensure first and foremost that they are in an appropriate environment. The structure and content of the conversation may be relevant, and adhering to dedicated communication strategies can be a wise choice for the physician and the interlocutor.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Communicating bad news to patients is one of the most stressful and challenging clinical tasks for any physician, regardless of his or her specialty. Delivering bad news to a patient or their close relative is demanding because the information provided during the dialogue can substantially alter the person’s perspective on life. This task is more frequent for physicians caring for oncology patients and can also affect the physician’s emotional state.

The manner in which bad news is communicated plays a significant role in the psychological burden on the patient, and various communication techniques and guidelines have been developed to enable physicians to perform this difficult task effectively.

Revealing bad news in person whenever possible, to address the emotional responses of patients or relatives, is part of the prevailing expert recommendations. However, it has been acknowledged that in certain situations, communicating bad news over the phone is more feasible.

Since the beginning of the COVID-19 pandemic, the disclosure of bad news over the phone has become a necessary substitute for in-person visits and an integral part of clinical practice worldwide. It remains to be clarified what the real psychological impact on patients and their closest relatives is when delivering bad news over the phone compared with delivering it in person.

Right and Wrong Ways

The most popular guideline for communicating bad news is SPIKES, a six-phase protocol with a special application for cancer patients. It is used in various countries (eg, the United States, France, and Germany) as a guide for this sensitive practice and for training in communication skills in this context. The SPIKES acronym refers to the following six recommended steps for delivering bad news:

• Setting: Set up the conversation.
• Perception: Assess the patient’s perception.
• Invitation: Ask the patient what he or she would like to know.
• Knowledge: Provide the patient with knowledge and information, breaking it down into small parts.
• Emotions: Acknowledge and empathetically address the patient’s emotions.
• Strategy and Summary: Summarize and define a medical action plan.

The lesson from SPIKES is that when a person experiences strong emotions, it is difficult to continue discussing anything, and they will struggle to hear anything. Allowing for silence is fundamental. In addition, empathy allows the patient to express his or her feelings and concerns, as well as provide support. The aim is not to argue but to allow the expression of emotions without criticism. However, these recommendations are primarily based on expert opinion and less on empirical evidence, due to the difficulty of studies in assessing patient outcomes in various phases of these protocols.

A recent study analyzed the differences in psychological distress between patients who received bad news over the phone vs those who received it in person. The study was a systematic review and meta-analysis.

The investigators examined 5944 studies, including 11 qualitative analysis studies, nine meta-analyses, and four randomized controlled trials.

In a set of studies ranging from moderate to good quality, no difference in psychological distress was found when bad news was disclosed over the phone compared with in person, regarding anxiety, depression, and posttraumatic stress disorder.

There was no average difference in patient satisfaction levels when bad news was delivered over the phone compared with in person. The risk for dissatisfaction was similar between groups.

Clinical Practice Guidelines

The demand for telemedicine, including the disclosure of bad news, is growing despite the limited knowledge of potential adverse effects. The results of existing studies suggest that the mode of disclosure may play a secondary role, and the manner in which bad news is communicated may be more important.

Therefore, it is paramount to prepare patients or their families for the possibility of receiving bad news well in advance and, during the conversation, to ensure first and foremost that they are in an appropriate environment. The structure and content of the conversation may be relevant, and adhering to dedicated communication strategies can be a wise choice for the physician and the interlocutor.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

A group of 16 Democratic legislators on the House Committee on Oversight and Reform has demanded in a letter that the drugmaker Pfizer present details on how the company is responding to shortages of the generic chemotherapy drugs carboplatin, cisplatin, and methotrexate.

In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.

A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”

What is the basis for concern?

All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.

What has the government done in response to the recent shortages?

The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.

What can the lawmakers expect to achieve with their letter?

By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”

Why did the committee target Pfizer specifically?

Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”

The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.

What is being demanded of Pfizer?

Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.

A group of 16 Democratic legislators on the House Committee on Oversight and Reform has demanded in a letter that the drugmaker Pfizer present details on how the company is responding to shortages of the generic chemotherapy drugs carboplatin, cisplatin, and methotrexate.

In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.

A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”

What is the basis for concern?

All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.

What has the government done in response to the recent shortages?

The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.

What can the lawmakers expect to achieve with their letter?

By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”

Why did the committee target Pfizer specifically?

Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”

The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.

What is being demanded of Pfizer?

Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.

A group of 16 Democratic legislators on the House Committee on Oversight and Reform has demanded in a letter that the drugmaker Pfizer present details on how the company is responding to shortages of the generic chemotherapy drugs carboplatin, cisplatin, and methotrexate.

In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.

A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”

What is the basis for concern?

All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.

What has the government done in response to the recent shortages?

The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.

What can the lawmakers expect to achieve with their letter?

By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”

Why did the committee target Pfizer specifically?

Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”

The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.

What is being demanded of Pfizer?

Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.