Randy Dotinga

Women across the world face high levels of financial burden from breast cancer, a new systematic review and analysis finds. While the burden of the disease is much higher in less-developed countries, about a third of women in Western nations like the United States say the disease has hurt their financial well-being.

When it comes to financial burden, patients with breast cancer are “a highly vulnerable patient population,” said study coauthor Kavitha Ranganathan, MD, of Brigham and Women’s Hospital, Boston, in an interview. “We need to be both strategic and comprehensive with our approach and use evidence-based methods to come up with these comprehensive solutions,” said Dr. Ranganathan, who noted that she’s hearing more from patients who face monetary hurdles.

The findings were published online in JAMA Network Open.

The researchers believe their analysis is the first to attempt to understand financial toxicity (FT) – excessive financial burden – in breast cancer on a global level. This turned out to be a challenge since there’s no standard way to measure FT.

One approach is to look at financial burden in terms of whether patients are suffering from “catastrophic expenditure,” Dr. Ranganathan said. “That’s what the World Bank and other top health and economic organizations have focused on. It means that the cost of care and – whatever it takes to get care – exceeds 10% of total annual household income.”

Another approach is more subjective and based on patient-reported outcomes, she said: “Are patients having to forgo basic subsistence needs like rent and food?”

For the report, researchers analyzed studies that use both approaches to measure FT from breast cancer. The studies came from high-income countries (n = 24, including 19 from the United States) and middle- and low-income countries (n = 10), and ranged in size from 5 to 2,445 subjects.

The analyzed studies were a range of cross-sectional (n = 26), prospective (n = 7), and retrospective designs (n = 1).

The authors pooled the data from 18 studies and estimated that the rate of patients with FT was 35.3% (14 studies, 27.3%-44.4%) in high-income countries and 78.8% (4 studies, 60.4%-90.0%) in the other countries.

The researchers also conducted a separate pooled analysis of only the U.S. studies (n = 11). It found that 34% (27%-43%) of subjects reported FT. The researchers also conducted a new analysis of Canada-only studies (n = 2) and found that 19% (9%-35%) reported FT.

The researchers weren’t able to provide insight into trends in FT in the United States prior to the period of the studies (2014-2021). But raw numbers suggest the percentage of patients facing financial challenges rose over that time, suggesting a possible increase in burden.

Previous research has suggested that breast cancer poses a higher financial burden than other chronic conditions. “Breast cancer care in particular may be associated with high FT given the need for screening and diagnosis, multidisciplinary care, and longitudinal follow-up,” the researchers write. They add that “notably, gender also affects financial security.”

As for limitations, the researchers report that they only analyzed studies in English, and there was a wide variation in approaches used to analyze FT. The analysis “did not account for different health care systems or control for health care–dedicated gross domestic product,” meaning that there’s no way to know for sure that rates were lower in nations with universal health care.

How could the new findings be useful? “They’re eye-opening for health policymakers. Whenever they see these numbers, they will say, ‘Wow, it is really a problem,’ and they’ll start thinking about solutions,” said study coauthor Rania A. Mekary, PhD, MSc, MSc, of Massachusetts College of Pharmacy and Health Sciences in Boston. “When you give them evidence-based data, then they will take it more seriously.”

The researchers call for interventions in several areas including education about early diagnosis and treatment of breast cancer, expansion of health care coverage, programs to help with nonmedical costs, and better resources for breast cancer care.

In an interview, Mary C. Politi, PhD, of Washington University, St. Louis, said the new report is useful “because it examines financial hardship internationally. Some people wonder whether financial hardship is a U.S. problem because of our health care system, which often relies on insurance and a lot of cost-sharing between insurance and patients. However, financial toxicity is prevalent across countries.”

And, she said, “the study is also useful because it encourages us to measure financial hardship and burden in a more uniform way so we can better compare and pool studies.”

Dr. Politi noted that there are ways to help patients now. “Most hospitals and health centers have staff who can talk to patients about their bills. Sometimes, a payment plan can be set up to space out payments,” she said. “Health care teams can try to consolidate care for patients on the same day to reduce parking expenses or time off for work or child care. Sometimes, changing to less expensive but effective generic medications is an option.”

The study authors received support from the National Cancer Institute, the United Nations Institute for Training and Research, the Global Surgery Foundation, the Harvard Global Health Institute, the Connors Center for Women’s Health and Gender Biology, the Center for Surgery and Public Health, and the National Endowment for Plastic Surgery. Dr. Ranganathan and Dr. Mekary report no disclosures. One coauthor reported a patent (BREAST-Q) and codevelopment of QPROMS, owned by Memorial Sloan Kettering Cancer Center. Another author reports salary support from Blue Cross Blue Shield of Michigan through the collaborative quality initiative known as Michigan Social Health Interventions to Eliminate Disparities. Dr. Politi has no disclosures.

Women across the world face high levels of financial burden from breast cancer, a new systematic review and analysis finds. While the burden of the disease is much higher in less-developed countries, about a third of women in Western nations like the United States say the disease has hurt their financial well-being.

When it comes to financial burden, patients with breast cancer are “a highly vulnerable patient population,” said study coauthor Kavitha Ranganathan, MD, of Brigham and Women’s Hospital, Boston, in an interview. “We need to be both strategic and comprehensive with our approach and use evidence-based methods to come up with these comprehensive solutions,” said Dr. Ranganathan, who noted that she’s hearing more from patients who face monetary hurdles.

The findings were published online in JAMA Network Open.

The researchers believe their analysis is the first to attempt to understand financial toxicity (FT) – excessive financial burden – in breast cancer on a global level. This turned out to be a challenge since there’s no standard way to measure FT.

One approach is to look at financial burden in terms of whether patients are suffering from “catastrophic expenditure,” Dr. Ranganathan said. “That’s what the World Bank and other top health and economic organizations have focused on. It means that the cost of care and – whatever it takes to get care – exceeds 10% of total annual household income.”

Another approach is more subjective and based on patient-reported outcomes, she said: “Are patients having to forgo basic subsistence needs like rent and food?”

For the report, researchers analyzed studies that use both approaches to measure FT from breast cancer. The studies came from high-income countries (n = 24, including 19 from the United States) and middle- and low-income countries (n = 10), and ranged in size from 5 to 2,445 subjects.

The analyzed studies were a range of cross-sectional (n = 26), prospective (n = 7), and retrospective designs (n = 1).

The authors pooled the data from 18 studies and estimated that the rate of patients with FT was 35.3% (14 studies, 27.3%-44.4%) in high-income countries and 78.8% (4 studies, 60.4%-90.0%) in the other countries.

The researchers also conducted a separate pooled analysis of only the U.S. studies (n = 11). It found that 34% (27%-43%) of subjects reported FT. The researchers also conducted a new analysis of Canada-only studies (n = 2) and found that 19% (9%-35%) reported FT.

The researchers weren’t able to provide insight into trends in FT in the United States prior to the period of the studies (2014-2021). But raw numbers suggest the percentage of patients facing financial challenges rose over that time, suggesting a possible increase in burden.

Previous research has suggested that breast cancer poses a higher financial burden than other chronic conditions. “Breast cancer care in particular may be associated with high FT given the need for screening and diagnosis, multidisciplinary care, and longitudinal follow-up,” the researchers write. They add that “notably, gender also affects financial security.”

As for limitations, the researchers report that they only analyzed studies in English, and there was a wide variation in approaches used to analyze FT. The analysis “did not account for different health care systems or control for health care–dedicated gross domestic product,” meaning that there’s no way to know for sure that rates were lower in nations with universal health care.

How could the new findings be useful? “They’re eye-opening for health policymakers. Whenever they see these numbers, they will say, ‘Wow, it is really a problem,’ and they’ll start thinking about solutions,” said study coauthor Rania A. Mekary, PhD, MSc, MSc, of Massachusetts College of Pharmacy and Health Sciences in Boston. “When you give them evidence-based data, then they will take it more seriously.”

The researchers call for interventions in several areas including education about early diagnosis and treatment of breast cancer, expansion of health care coverage, programs to help with nonmedical costs, and better resources for breast cancer care.

In an interview, Mary C. Politi, PhD, of Washington University, St. Louis, said the new report is useful “because it examines financial hardship internationally. Some people wonder whether financial hardship is a U.S. problem because of our health care system, which often relies on insurance and a lot of cost-sharing between insurance and patients. However, financial toxicity is prevalent across countries.”

And, she said, “the study is also useful because it encourages us to measure financial hardship and burden in a more uniform way so we can better compare and pool studies.”

Dr. Politi noted that there are ways to help patients now. “Most hospitals and health centers have staff who can talk to patients about their bills. Sometimes, a payment plan can be set up to space out payments,” she said. “Health care teams can try to consolidate care for patients on the same day to reduce parking expenses or time off for work or child care. Sometimes, changing to less expensive but effective generic medications is an option.”

The study authors received support from the National Cancer Institute, the United Nations Institute for Training and Research, the Global Surgery Foundation, the Harvard Global Health Institute, the Connors Center for Women’s Health and Gender Biology, the Center for Surgery and Public Health, and the National Endowment for Plastic Surgery. Dr. Ranganathan and Dr. Mekary report no disclosures. One coauthor reported a patent (BREAST-Q) and codevelopment of QPROMS, owned by Memorial Sloan Kettering Cancer Center. Another author reports salary support from Blue Cross Blue Shield of Michigan through the collaborative quality initiative known as Michigan Social Health Interventions to Eliminate Disparities. Dr. Politi has no disclosures.

Women across the world face high levels of financial burden from breast cancer, a new systematic review and analysis finds. While the burden of the disease is much higher in less-developed countries, about a third of women in Western nations like the United States say the disease has hurt their financial well-being.

When it comes to financial burden, patients with breast cancer are “a highly vulnerable patient population,” said study coauthor Kavitha Ranganathan, MD, of Brigham and Women’s Hospital, Boston, in an interview. “We need to be both strategic and comprehensive with our approach and use evidence-based methods to come up with these comprehensive solutions,” said Dr. Ranganathan, who noted that she’s hearing more from patients who face monetary hurdles.

The findings were published online in JAMA Network Open.

The researchers believe their analysis is the first to attempt to understand financial toxicity (FT) – excessive financial burden – in breast cancer on a global level. This turned out to be a challenge since there’s no standard way to measure FT.

One approach is to look at financial burden in terms of whether patients are suffering from “catastrophic expenditure,” Dr. Ranganathan said. “That’s what the World Bank and other top health and economic organizations have focused on. It means that the cost of care and – whatever it takes to get care – exceeds 10% of total annual household income.”

Another approach is more subjective and based on patient-reported outcomes, she said: “Are patients having to forgo basic subsistence needs like rent and food?”

For the report, researchers analyzed studies that use both approaches to measure FT from breast cancer. The studies came from high-income countries (n = 24, including 19 from the United States) and middle- and low-income countries (n = 10), and ranged in size from 5 to 2,445 subjects.

The analyzed studies were a range of cross-sectional (n = 26), prospective (n = 7), and retrospective designs (n = 1).

The authors pooled the data from 18 studies and estimated that the rate of patients with FT was 35.3% (14 studies, 27.3%-44.4%) in high-income countries and 78.8% (4 studies, 60.4%-90.0%) in the other countries.

The researchers also conducted a separate pooled analysis of only the U.S. studies (n = 11). It found that 34% (27%-43%) of subjects reported FT. The researchers also conducted a new analysis of Canada-only studies (n = 2) and found that 19% (9%-35%) reported FT.

The researchers weren’t able to provide insight into trends in FT in the United States prior to the period of the studies (2014-2021). But raw numbers suggest the percentage of patients facing financial challenges rose over that time, suggesting a possible increase in burden.

Previous research has suggested that breast cancer poses a higher financial burden than other chronic conditions. “Breast cancer care in particular may be associated with high FT given the need for screening and diagnosis, multidisciplinary care, and longitudinal follow-up,” the researchers write. They add that “notably, gender also affects financial security.”

As for limitations, the researchers report that they only analyzed studies in English, and there was a wide variation in approaches used to analyze FT. The analysis “did not account for different health care systems or control for health care–dedicated gross domestic product,” meaning that there’s no way to know for sure that rates were lower in nations with universal health care.

How could the new findings be useful? “They’re eye-opening for health policymakers. Whenever they see these numbers, they will say, ‘Wow, it is really a problem,’ and they’ll start thinking about solutions,” said study coauthor Rania A. Mekary, PhD, MSc, MSc, of Massachusetts College of Pharmacy and Health Sciences in Boston. “When you give them evidence-based data, then they will take it more seriously.”

The researchers call for interventions in several areas including education about early diagnosis and treatment of breast cancer, expansion of health care coverage, programs to help with nonmedical costs, and better resources for breast cancer care.

In an interview, Mary C. Politi, PhD, of Washington University, St. Louis, said the new report is useful “because it examines financial hardship internationally. Some people wonder whether financial hardship is a U.S. problem because of our health care system, which often relies on insurance and a lot of cost-sharing between insurance and patients. However, financial toxicity is prevalent across countries.”

And, she said, “the study is also useful because it encourages us to measure financial hardship and burden in a more uniform way so we can better compare and pool studies.”

Dr. Politi noted that there are ways to help patients now. “Most hospitals and health centers have staff who can talk to patients about their bills. Sometimes, a payment plan can be set up to space out payments,” she said. “Health care teams can try to consolidate care for patients on the same day to reduce parking expenses or time off for work or child care. Sometimes, changing to less expensive but effective generic medications is an option.”

The study authors received support from the National Cancer Institute, the United Nations Institute for Training and Research, the Global Surgery Foundation, the Harvard Global Health Institute, the Connors Center for Women’s Health and Gender Biology, the Center for Surgery and Public Health, and the National Endowment for Plastic Surgery. Dr. Ranganathan and Dr. Mekary report no disclosures. One coauthor reported a patent (BREAST-Q) and codevelopment of QPROMS, owned by Memorial Sloan Kettering Cancer Center. Another author reports salary support from Blue Cross Blue Shield of Michigan through the collaborative quality initiative known as Michigan Social Health Interventions to Eliminate Disparities. Dr. Politi has no disclosures.

Thanks to treatment advancements, patients with chronic lymphocytic leukemia (CLL) are living much longer – and at greater risk of developing other types of cancer. A new Dutch study has found that patients with CLL face higher risks of second primary malignancies (SPM) than the rest of the population, especially those who were treated with antineoplastic therapy.

The report, which appeared in January in Blood Cancer Journal, found that patients diagnosed with CLL between 1989 and 2019 were 63% more likely to were diagnosed with SPM than a matched population: standardized incidence ratio = 1.63, 95% confidence interval (CI), 1.59-1.68.

“Our results provide patients and their treating physicians with an overview of the risk of SPM development. This information can be used in treatment decision-making and for planning appropriate surveillance activities and interventions,” study lead author Lina van der Straten, MD, PhD, of the Albert Schweitzer Hospital and Erasmus University Medical Center in the Netherlands, said in an interview.

Ohio State University hematologist David Bond, MD, who’s familiar with the findings, said in an interview that “it’s been well-established that patients with CLL are at increased risk for second primary malignancies. This is thought to be due to impaired immune surveillance and possibly carcinogenic effects of CLL treatments.” It’s not clear, he said, “whether the rate of second cancers differs between chemoimmunotherapy-treated patients and those receiving newer oral kinase inhibitors.”

Previous research into CLL and SPM has been sparse, Dr. van der Straten said, and most studies haven’t looked at SPM over time and taken into account the widespread use of chemoimmunotherapy and agents such as ibrutinib and venetoclax.

It’s important to study this topic, she said, since “cancers diagnosed after the CLL diagnosis can outweigh the improved longevity and contribute to excess morbidity and mortality in long-term CLL survivors.”

With the help of the Netherlands Cancer Registry, researchers tracked 24,815 patients with CLL who were diagnosed over the 20-year period; 4,369 developed SPM. “We demonstrated that the risk of SPM development was higher than in the general population with an excess of 125 malignancies per 10,000 person-years in the CLL cohort,” Dr. van der Straten said. “The risk of SPM development was found to be heightened in solid and hematological cancers. Patients with CLL had an increased risk of developing cancers at the following sites or types: skin, acute myeloid leukemia, soft-tissue sarcomas, thyroid, kidney, unknown primary localization, non-Hodgkin lymphomas, lung and bronchus, and colon and rectum.”

Specifically, the study reports that “elevated risk was observed for solid (SIR = 1.67; 95% CI, 1.65-1.75) and hematological SPMs (SIR = 1.42; 95% CI, 1.24-1.62). The highest risk for SPMs was noted beyond 5 years post diagnosis (SIR = 1.70; 95% CI, 1.62-1.77), for male individuals (SIR = 1.70; 95% CI, 1.64-1.77), and patients aged 18-69 years (SR = 1.92; 95% CI, 1.79-2.05).

“Patients with CLL exposed to treatment have a higher risk of SPM development than patients who will never receive therapy,” Dr. van der Straten said. Research has shown that “treatment with fludarabine, cyclophosphamide, and rituximab has been associated with a 2.38 increased risk for SPM development, particularly acute myeloid leukemia. Indeed, we found an increased risk for hematological malignancies in patients diagnosed between 2003-2009 and 2010-2019, which might be explained by the broader administration of fludarabine-based strategies in these calendar periods.”

Multiple factors could explain the higher risk of SPM in patients with CLL, including “a dysregulated immune system, treatment-related effects, and surveillance bias,” Dr. van der Straten said. “In addition, it is proposed that the immune dysfunctional nature of CLL might enhance the effect of common carcinogens, such as UV exposure and smoking, in increasing the probability of skin and respiratory cancers.”

She added that “the risk and the spectrum of SPMs were comparable for the 2003-2009 and 2010-2019 periods, suggesting that both the introduction of chemoimmunotherapy and, in part, targeted therapies did not dramatically alter the SPM landscape. However, due to the short follow-up period for the small cohort of patients receiving targeted therapies, further research is warranted.”

Dr. Bond said the findings “are largely in line with prior studies and strengthen their conclusions. Immune surveillance appears to be critical to reducing the risk for some but not all malignancies including lung cancer and melanoma, and the treatments given for CLL can cause immune suppression and thus may increase the risk.”

Moving forward, he said, “this research highlights the importance of second cancers to patients with CLL. It also highlights the need for secondary cancer screening for CLL patients, patient education to avoid known cancer risk factors including smoking and excess UV light exposure, and the need as a field to continue to invest in research into characteristics of second cancers and mitigation strategies.”

Study funding was not reported. The authors and Dr. Bond report no disclosures.

Thanks to treatment advancements, patients with chronic lymphocytic leukemia (CLL) are living much longer – and at greater risk of developing other types of cancer. A new Dutch study has found that patients with CLL face higher risks of second primary malignancies (SPM) than the rest of the population, especially those who were treated with antineoplastic therapy.

The report, which appeared in January in Blood Cancer Journal, found that patients diagnosed with CLL between 1989 and 2019 were 63% more likely to were diagnosed with SPM than a matched population: standardized incidence ratio = 1.63, 95% confidence interval (CI), 1.59-1.68.

“Our results provide patients and their treating physicians with an overview of the risk of SPM development. This information can be used in treatment decision-making and for planning appropriate surveillance activities and interventions,” study lead author Lina van der Straten, MD, PhD, of the Albert Schweitzer Hospital and Erasmus University Medical Center in the Netherlands, said in an interview.

Ohio State University hematologist David Bond, MD, who’s familiar with the findings, said in an interview that “it’s been well-established that patients with CLL are at increased risk for second primary malignancies. This is thought to be due to impaired immune surveillance and possibly carcinogenic effects of CLL treatments.” It’s not clear, he said, “whether the rate of second cancers differs between chemoimmunotherapy-treated patients and those receiving newer oral kinase inhibitors.”

Previous research into CLL and SPM has been sparse, Dr. van der Straten said, and most studies haven’t looked at SPM over time and taken into account the widespread use of chemoimmunotherapy and agents such as ibrutinib and venetoclax.

It’s important to study this topic, she said, since “cancers diagnosed after the CLL diagnosis can outweigh the improved longevity and contribute to excess morbidity and mortality in long-term CLL survivors.”

With the help of the Netherlands Cancer Registry, researchers tracked 24,815 patients with CLL who were diagnosed over the 20-year period; 4,369 developed SPM. “We demonstrated that the risk of SPM development was higher than in the general population with an excess of 125 malignancies per 10,000 person-years in the CLL cohort,” Dr. van der Straten said. “The risk of SPM development was found to be heightened in solid and hematological cancers. Patients with CLL had an increased risk of developing cancers at the following sites or types: skin, acute myeloid leukemia, soft-tissue sarcomas, thyroid, kidney, unknown primary localization, non-Hodgkin lymphomas, lung and bronchus, and colon and rectum.”

Specifically, the study reports that “elevated risk was observed for solid (SIR = 1.67; 95% CI, 1.65-1.75) and hematological SPMs (SIR = 1.42; 95% CI, 1.24-1.62). The highest risk for SPMs was noted beyond 5 years post diagnosis (SIR = 1.70; 95% CI, 1.62-1.77), for male individuals (SIR = 1.70; 95% CI, 1.64-1.77), and patients aged 18-69 years (SR = 1.92; 95% CI, 1.79-2.05).

“Patients with CLL exposed to treatment have a higher risk of SPM development than patients who will never receive therapy,” Dr. van der Straten said. Research has shown that “treatment with fludarabine, cyclophosphamide, and rituximab has been associated with a 2.38 increased risk for SPM development, particularly acute myeloid leukemia. Indeed, we found an increased risk for hematological malignancies in patients diagnosed between 2003-2009 and 2010-2019, which might be explained by the broader administration of fludarabine-based strategies in these calendar periods.”

Multiple factors could explain the higher risk of SPM in patients with CLL, including “a dysregulated immune system, treatment-related effects, and surveillance bias,” Dr. van der Straten said. “In addition, it is proposed that the immune dysfunctional nature of CLL might enhance the effect of common carcinogens, such as UV exposure and smoking, in increasing the probability of skin and respiratory cancers.”

She added that “the risk and the spectrum of SPMs were comparable for the 2003-2009 and 2010-2019 periods, suggesting that both the introduction of chemoimmunotherapy and, in part, targeted therapies did not dramatically alter the SPM landscape. However, due to the short follow-up period for the small cohort of patients receiving targeted therapies, further research is warranted.”

Dr. Bond said the findings “are largely in line with prior studies and strengthen their conclusions. Immune surveillance appears to be critical to reducing the risk for some but not all malignancies including lung cancer and melanoma, and the treatments given for CLL can cause immune suppression and thus may increase the risk.”

Moving forward, he said, “this research highlights the importance of second cancers to patients with CLL. It also highlights the need for secondary cancer screening for CLL patients, patient education to avoid known cancer risk factors including smoking and excess UV light exposure, and the need as a field to continue to invest in research into characteristics of second cancers and mitigation strategies.”

Study funding was not reported. The authors and Dr. Bond report no disclosures.

Thanks to treatment advancements, patients with chronic lymphocytic leukemia (CLL) are living much longer – and at greater risk of developing other types of cancer. A new Dutch study has found that patients with CLL face higher risks of second primary malignancies (SPM) than the rest of the population, especially those who were treated with antineoplastic therapy.

The report, which appeared in January in Blood Cancer Journal, found that patients diagnosed with CLL between 1989 and 2019 were 63% more likely to were diagnosed with SPM than a matched population: standardized incidence ratio = 1.63, 95% confidence interval (CI), 1.59-1.68.

“Our results provide patients and their treating physicians with an overview of the risk of SPM development. This information can be used in treatment decision-making and for planning appropriate surveillance activities and interventions,” study lead author Lina van der Straten, MD, PhD, of the Albert Schweitzer Hospital and Erasmus University Medical Center in the Netherlands, said in an interview.

Ohio State University hematologist David Bond, MD, who’s familiar with the findings, said in an interview that “it’s been well-established that patients with CLL are at increased risk for second primary malignancies. This is thought to be due to impaired immune surveillance and possibly carcinogenic effects of CLL treatments.” It’s not clear, he said, “whether the rate of second cancers differs between chemoimmunotherapy-treated patients and those receiving newer oral kinase inhibitors.”

Previous research into CLL and SPM has been sparse, Dr. van der Straten said, and most studies haven’t looked at SPM over time and taken into account the widespread use of chemoimmunotherapy and agents such as ibrutinib and venetoclax.

It’s important to study this topic, she said, since “cancers diagnosed after the CLL diagnosis can outweigh the improved longevity and contribute to excess morbidity and mortality in long-term CLL survivors.”

With the help of the Netherlands Cancer Registry, researchers tracked 24,815 patients with CLL who were diagnosed over the 20-year period; 4,369 developed SPM. “We demonstrated that the risk of SPM development was higher than in the general population with an excess of 125 malignancies per 10,000 person-years in the CLL cohort,” Dr. van der Straten said. “The risk of SPM development was found to be heightened in solid and hematological cancers. Patients with CLL had an increased risk of developing cancers at the following sites or types: skin, acute myeloid leukemia, soft-tissue sarcomas, thyroid, kidney, unknown primary localization, non-Hodgkin lymphomas, lung and bronchus, and colon and rectum.”

Specifically, the study reports that “elevated risk was observed for solid (SIR = 1.67; 95% CI, 1.65-1.75) and hematological SPMs (SIR = 1.42; 95% CI, 1.24-1.62). The highest risk for SPMs was noted beyond 5 years post diagnosis (SIR = 1.70; 95% CI, 1.62-1.77), for male individuals (SIR = 1.70; 95% CI, 1.64-1.77), and patients aged 18-69 years (SR = 1.92; 95% CI, 1.79-2.05).

“Patients with CLL exposed to treatment have a higher risk of SPM development than patients who will never receive therapy,” Dr. van der Straten said. Research has shown that “treatment with fludarabine, cyclophosphamide, and rituximab has been associated with a 2.38 increased risk for SPM development, particularly acute myeloid leukemia. Indeed, we found an increased risk for hematological malignancies in patients diagnosed between 2003-2009 and 2010-2019, which might be explained by the broader administration of fludarabine-based strategies in these calendar periods.”

Multiple factors could explain the higher risk of SPM in patients with CLL, including “a dysregulated immune system, treatment-related effects, and surveillance bias,” Dr. van der Straten said. “In addition, it is proposed that the immune dysfunctional nature of CLL might enhance the effect of common carcinogens, such as UV exposure and smoking, in increasing the probability of skin and respiratory cancers.”

She added that “the risk and the spectrum of SPMs were comparable for the 2003-2009 and 2010-2019 periods, suggesting that both the introduction of chemoimmunotherapy and, in part, targeted therapies did not dramatically alter the SPM landscape. However, due to the short follow-up period for the small cohort of patients receiving targeted therapies, further research is warranted.”

Dr. Bond said the findings “are largely in line with prior studies and strengthen their conclusions. Immune surveillance appears to be critical to reducing the risk for some but not all malignancies including lung cancer and melanoma, and the treatments given for CLL can cause immune suppression and thus may increase the risk.”

Moving forward, he said, “this research highlights the importance of second cancers to patients with CLL. It also highlights the need for secondary cancer screening for CLL patients, patient education to avoid known cancer risk factors including smoking and excess UV light exposure, and the need as a field to continue to invest in research into characteristics of second cancers and mitigation strategies.”

Study funding was not reported. The authors and Dr. Bond report no disclosures.

Infants born to women infected with the hepatitis C virus (HCV) faced twice the risk of stays in the neonatal ICU (NICU) and 2.7 times the risk of low birth weight, a new analysis finds, even when researchers adjusted their data to control for injectable drug use and maternal medical comorbidity.

Clinicians should be “aware that the infants of pregnant people with HCV may have a high rate of need for higher-level pediatric care,” said Brenna L. Hughes, MD, MSc, chief of maternal fetal medicine at Duke University Medical Center, Durham, N.C. She spoke in an interview about the findings, which were presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

As Dr. Hughes noted, “HCV remains a serious problem in pregnancy because it often goes undiagnosed and/or untreated prior to pregnancy. It can be passed to infants, and this can cause significant health-related outcomes for children as they age.”

For the multicenter U.S. study, researchers identified 249 pregnant mothers with HCV from a 2012-2018 cohort and matched them by gestational age to controls (n = 486). The average age was 28; 71.1% of the cases were non-Hispanic White versus 41.6% of the controls; 8.4% of cases were non-Hispanic Black versus 32.1% of controls (P < .001 for race/ethnicity analysis); and 73% of cases were smokers versus 18% of controls (P < .001). More than 19% of cases reported injectable drug use during pregnancy versus 0.2% of controls (P < .001).

The researchers adjusted their findings for maternal age, body mass index, injectable drug use, and maternal comorbidity.

An earlier analysis of the study data found that 6% of pregnant women with HCV passed it on to their infants, especially those with high levels of virus in their systems. For the new study, researchers focused on various outcomes to test the assumption that “adverse pregnancy outcomes associated with HCV are related to prematurity or to ongoing use of injection drugs,” Dr. Hughes said.

There was no increase in rates of preterm birth or adverse maternal outcomes in the HCV cases. However, infants born to women with HCV were more likely than the controls to require a stay in the NICU (45% vs. 19%; adjusted relative risk, 1.99; 95% confidence interval, 1.54-2.58). They were also more likely to have lower birth weights (small for gestational age < 5th percentile) (10.6% vs. 3.1%; ARR, 2.72; 95% CI, 1.38-5.34).

No difference in outcomes was seen when HCV cases with viremia (33%) were excluded.

“The most surprising finding was that the need for higher-level pediatric care was so high even though there wasn’t an increased risk of prematurity,” Dr. Hughes said.

She added it’s not clear why NICU stays and low birth weights were more common in infants of women with HCV. “It is possible that the higher risk of need for higher-level pediatric care was related to a need for observation or treatment due to use of opioid replacement therapies with opioid agonists.” As for lower birth weight, “there may be other unmeasured risk factors.”

Tatyana Kushner, MD, MSCE, of the division of liver diseases at Icahn School of Medicine at Mount Sinai, New York, said in an interview that the study adds to limited data about HCV in pregnancy. “These findings have been demonstrated in prior studies, and it would be important to tease apart whether [low birth weight] is related to the virus itself or more related to other confounding associated factors such as maternal substance use as well as other associated social determinants of health among women with HCV.”

As for the study’s message, Dr. Kushner said it makes it clear that “hepatitis C adversely impacts outcomes of pregnancy and it is important to identify women of childbearing age for treatment early, ideally prior to pregnancy, in order to improve their pregnancy outcomes. In addition, treatment of hepatitis C during pregnancy should be explored further to determine if treatment during pregnancy can improve outcomes.”

At the moment, she said, “there are ongoing studies to delineate the safety and efficacy of hepatitis C treatment during pregnancy. Given that we are screening for hepatitis C during pregnancy, we need clear recommendations on the use of direct-acting antivirals in people who screen positive.”

The study was funded by the National Institute of Child Health and Human Development. The authors have no disclosures. Dr. Kushner disclosed research support (Gilead) and advisory board service (Gilead, AbbVie, Bausch, GlaxoSmithKline, and Eiger).

Infants born to women infected with the hepatitis C virus (HCV) faced twice the risk of stays in the neonatal ICU (NICU) and 2.7 times the risk of low birth weight, a new analysis finds, even when researchers adjusted their data to control for injectable drug use and maternal medical comorbidity.

Clinicians should be “aware that the infants of pregnant people with HCV may have a high rate of need for higher-level pediatric care,” said Brenna L. Hughes, MD, MSc, chief of maternal fetal medicine at Duke University Medical Center, Durham, N.C. She spoke in an interview about the findings, which were presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

As Dr. Hughes noted, “HCV remains a serious problem in pregnancy because it often goes undiagnosed and/or untreated prior to pregnancy. It can be passed to infants, and this can cause significant health-related outcomes for children as they age.”

For the multicenter U.S. study, researchers identified 249 pregnant mothers with HCV from a 2012-2018 cohort and matched them by gestational age to controls (n = 486). The average age was 28; 71.1% of the cases were non-Hispanic White versus 41.6% of the controls; 8.4% of cases were non-Hispanic Black versus 32.1% of controls (P < .001 for race/ethnicity analysis); and 73% of cases were smokers versus 18% of controls (P < .001). More than 19% of cases reported injectable drug use during pregnancy versus 0.2% of controls (P < .001).

The researchers adjusted their findings for maternal age, body mass index, injectable drug use, and maternal comorbidity.

An earlier analysis of the study data found that 6% of pregnant women with HCV passed it on to their infants, especially those with high levels of virus in their systems. For the new study, researchers focused on various outcomes to test the assumption that “adverse pregnancy outcomes associated with HCV are related to prematurity or to ongoing use of injection drugs,” Dr. Hughes said.

There was no increase in rates of preterm birth or adverse maternal outcomes in the HCV cases. However, infants born to women with HCV were more likely than the controls to require a stay in the NICU (45% vs. 19%; adjusted relative risk, 1.99; 95% confidence interval, 1.54-2.58). They were also more likely to have lower birth weights (small for gestational age < 5th percentile) (10.6% vs. 3.1%; ARR, 2.72; 95% CI, 1.38-5.34).

No difference in outcomes was seen when HCV cases with viremia (33%) were excluded.

“The most surprising finding was that the need for higher-level pediatric care was so high even though there wasn’t an increased risk of prematurity,” Dr. Hughes said.

She added it’s not clear why NICU stays and low birth weights were more common in infants of women with HCV. “It is possible that the higher risk of need for higher-level pediatric care was related to a need for observation or treatment due to use of opioid replacement therapies with opioid agonists.” As for lower birth weight, “there may be other unmeasured risk factors.”

Tatyana Kushner, MD, MSCE, of the division of liver diseases at Icahn School of Medicine at Mount Sinai, New York, said in an interview that the study adds to limited data about HCV in pregnancy. “These findings have been demonstrated in prior studies, and it would be important to tease apart whether [low birth weight] is related to the virus itself or more related to other confounding associated factors such as maternal substance use as well as other associated social determinants of health among women with HCV.”

As for the study’s message, Dr. Kushner said it makes it clear that “hepatitis C adversely impacts outcomes of pregnancy and it is important to identify women of childbearing age for treatment early, ideally prior to pregnancy, in order to improve their pregnancy outcomes. In addition, treatment of hepatitis C during pregnancy should be explored further to determine if treatment during pregnancy can improve outcomes.”

At the moment, she said, “there are ongoing studies to delineate the safety and efficacy of hepatitis C treatment during pregnancy. Given that we are screening for hepatitis C during pregnancy, we need clear recommendations on the use of direct-acting antivirals in people who screen positive.”

The study was funded by the National Institute of Child Health and Human Development. The authors have no disclosures. Dr. Kushner disclosed research support (Gilead) and advisory board service (Gilead, AbbVie, Bausch, GlaxoSmithKline, and Eiger).

Infants born to women infected with the hepatitis C virus (HCV) faced twice the risk of stays in the neonatal ICU (NICU) and 2.7 times the risk of low birth weight, a new analysis finds, even when researchers adjusted their data to control for injectable drug use and maternal medical comorbidity.

Clinicians should be “aware that the infants of pregnant people with HCV may have a high rate of need for higher-level pediatric care,” said Brenna L. Hughes, MD, MSc, chief of maternal fetal medicine at Duke University Medical Center, Durham, N.C. She spoke in an interview about the findings, which were presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

As Dr. Hughes noted, “HCV remains a serious problem in pregnancy because it often goes undiagnosed and/or untreated prior to pregnancy. It can be passed to infants, and this can cause significant health-related outcomes for children as they age.”

For the multicenter U.S. study, researchers identified 249 pregnant mothers with HCV from a 2012-2018 cohort and matched them by gestational age to controls (n = 486). The average age was 28; 71.1% of the cases were non-Hispanic White versus 41.6% of the controls; 8.4% of cases were non-Hispanic Black versus 32.1% of controls (P < .001 for race/ethnicity analysis); and 73% of cases were smokers versus 18% of controls (P < .001). More than 19% of cases reported injectable drug use during pregnancy versus 0.2% of controls (P < .001).

The researchers adjusted their findings for maternal age, body mass index, injectable drug use, and maternal comorbidity.

An earlier analysis of the study data found that 6% of pregnant women with HCV passed it on to their infants, especially those with high levels of virus in their systems. For the new study, researchers focused on various outcomes to test the assumption that “adverse pregnancy outcomes associated with HCV are related to prematurity or to ongoing use of injection drugs,” Dr. Hughes said.

There was no increase in rates of preterm birth or adverse maternal outcomes in the HCV cases. However, infants born to women with HCV were more likely than the controls to require a stay in the NICU (45% vs. 19%; adjusted relative risk, 1.99; 95% confidence interval, 1.54-2.58). They were also more likely to have lower birth weights (small for gestational age < 5th percentile) (10.6% vs. 3.1%; ARR, 2.72; 95% CI, 1.38-5.34).

No difference in outcomes was seen when HCV cases with viremia (33%) were excluded.

“The most surprising finding was that the need for higher-level pediatric care was so high even though there wasn’t an increased risk of prematurity,” Dr. Hughes said.

She added it’s not clear why NICU stays and low birth weights were more common in infants of women with HCV. “It is possible that the higher risk of need for higher-level pediatric care was related to a need for observation or treatment due to use of opioid replacement therapies with opioid agonists.” As for lower birth weight, “there may be other unmeasured risk factors.”

Tatyana Kushner, MD, MSCE, of the division of liver diseases at Icahn School of Medicine at Mount Sinai, New York, said in an interview that the study adds to limited data about HCV in pregnancy. “These findings have been demonstrated in prior studies, and it would be important to tease apart whether [low birth weight] is related to the virus itself or more related to other confounding associated factors such as maternal substance use as well as other associated social determinants of health among women with HCV.”

As for the study’s message, Dr. Kushner said it makes it clear that “hepatitis C adversely impacts outcomes of pregnancy and it is important to identify women of childbearing age for treatment early, ideally prior to pregnancy, in order to improve their pregnancy outcomes. In addition, treatment of hepatitis C during pregnancy should be explored further to determine if treatment during pregnancy can improve outcomes.”

At the moment, she said, “there are ongoing studies to delineate the safety and efficacy of hepatitis C treatment during pregnancy. Given that we are screening for hepatitis C during pregnancy, we need clear recommendations on the use of direct-acting antivirals in people who screen positive.”

The study was funded by the National Institute of Child Health and Human Development. The authors have no disclosures. Dr. Kushner disclosed research support (Gilead) and advisory board service (Gilead, AbbVie, Bausch, GlaxoSmithKline, and Eiger).

A new randomized, open-label French trial offers more evidence that the discontinuation of oxytocin treatment after the earliest stages of labor may be safe. Stopping oxytocin didn’t appear to affect neonatal outcomes, compared with continual use of the medication. However, the first stage of labor lasted slightly longer – not surprisingly – in those in the intervention group, and many of those who stopped oxytocin treatment resumed it later.

“Our trial did not show any impact of oxytocin discontinuation in the active [labor] stage on neonatal morbidity cesarean delivery, postpartum hemorrhage, birth experience, and postpartum depression,” said Aude Girault, MD, PhD, of Paris Cité University, in a presentation in San Francisco at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The goal of the STOPOXY study is to build upon previous research that found oxytocin discontinuation didn’t boost the risk of cesarean delivery rates, uterine hyperstimulation, and abnormal fetal heart rate, Dr. Girault said. “These studies were underpowered to show any effects on neonatal morbidity,” so she and colleagues decided to dig deeper into the issue by launching the new trial.

From 2020 to 2022, researchers assigned 2,367 women who received oxytocin before 4 centimeters dilation to either continue with the drug (n = 1,192) or discontinue it before reaching 6 centimeters dilation (n = 1,175). Overall, the women were pregnant for the first time (around 55%) with a median age around 32 years and body mass index around 24.1 kg/m². All had live, singleton, full-term babies.

More than a third – 37% – of those who discontinued oxytocin resumed treatment with the medication, while 5% of those in the control group stopped taking it.

The neonatal morbidity rate – defined via a composite variable based on umbilical arterial pH, umbilical arterial lactates, Apgar score, and/or neonatal ICU admission – was 10.0% in the intervention group and 10.1% in the control group (P = .94), the researchers reported. Cesarean delivery rates were similar (18.8% vs. 16.5%, respectively; P = .22). Apart from the duration of the active first stage, which was significantly higher in the intervention group (100 min [ interquartile range, 50-208 min] vs. 90 min [IQR, 45-150 min]; P = .001), there were no significant differences between the groups.

Dr. Girault said this increase in labor duration was “moderate and clinically debatable.”

In an interview, oncologist-gynecologist George Saade, MD, of the University of Texas Medical Branch, Galveston, noted that “oxytocin is frequently used for either induction or augmentation of labor ... with the goal of improving maternal and neonatal outcomes.”

Oxytocin itself is not expensive, Dr. Saade said. “However, when it is given, the patient requires more monitoring, which may increase cost.”

There’s debate over the proper use of oxytocin, which is available in a synthetic version as Pitocin, and researchers have been trying to understand whether it can safely be discontinued early in labor.

Potential side effects of oxytocin include heart disorders such as arrhythmia, asphyxia, neonatal seizure, and jaundice, low Apgar score, and fetal death. A boxed warning says: “Because the available data are inadequate to evaluate the benefits-to-risks considerations, oxytocin is not indicated for elective induction of labor.”

However, “overall oxytocin is commonly used and very safe as long as careful protocols are followed,” David N. Hackney, MD, MS, of University Hospitals Cleveland, said in an interview. “The medication itself does not have many negative side effects. With very high doses there can be a concern for water intoxication, though this is clinically very uncommon. Some prior studies have raised concerns about the use of oxytocin and subsequent long-term neurodevelopmental outcomes, though these associations are likely confounders and the mainstream opinion is that these are not truly biologically causative associations.”

A 2021 study in The BMJ randomly assigned 1,200 women to continue or discontinue oxytocin. There was a slight increase in cesarean sections in the discontinuation group but significantly lower risks of uterine hyperstimulation and abnormal fetal heart rate.

Dr. Hackney, who didn’t take part in the new study, said the trial is “well conducted and well executed.” However, it needs peer review before any of its findings should change practice.

He added that differences in delivery protocols between the United States and France should be considered. As he noted, Dr. Girault mentioned in a Q&A after her presentation that delayed second-stage labor is more common in France than in the United States.

The study was funded by the French National Ministry of Health. Disclosures for the authors were not provided. Dr. Saade and Dr. Hackney have no disclosures.

A new randomized, open-label French trial offers more evidence that the discontinuation of oxytocin treatment after the earliest stages of labor may be safe. Stopping oxytocin didn’t appear to affect neonatal outcomes, compared with continual use of the medication. However, the first stage of labor lasted slightly longer – not surprisingly – in those in the intervention group, and many of those who stopped oxytocin treatment resumed it later.

“Our trial did not show any impact of oxytocin discontinuation in the active [labor] stage on neonatal morbidity cesarean delivery, postpartum hemorrhage, birth experience, and postpartum depression,” said Aude Girault, MD, PhD, of Paris Cité University, in a presentation in San Francisco at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The goal of the STOPOXY study is to build upon previous research that found oxytocin discontinuation didn’t boost the risk of cesarean delivery rates, uterine hyperstimulation, and abnormal fetal heart rate, Dr. Girault said. “These studies were underpowered to show any effects on neonatal morbidity,” so she and colleagues decided to dig deeper into the issue by launching the new trial.

From 2020 to 2022, researchers assigned 2,367 women who received oxytocin before 4 centimeters dilation to either continue with the drug (n = 1,192) or discontinue it before reaching 6 centimeters dilation (n = 1,175). Overall, the women were pregnant for the first time (around 55%) with a median age around 32 years and body mass index around 24.1 kg/m². All had live, singleton, full-term babies.

More than a third – 37% – of those who discontinued oxytocin resumed treatment with the medication, while 5% of those in the control group stopped taking it.

The neonatal morbidity rate – defined via a composite variable based on umbilical arterial pH, umbilical arterial lactates, Apgar score, and/or neonatal ICU admission – was 10.0% in the intervention group and 10.1% in the control group (P = .94), the researchers reported. Cesarean delivery rates were similar (18.8% vs. 16.5%, respectively; P = .22). Apart from the duration of the active first stage, which was significantly higher in the intervention group (100 min [ interquartile range, 50-208 min] vs. 90 min [IQR, 45-150 min]; P = .001), there were no significant differences between the groups.

Dr. Girault said this increase in labor duration was “moderate and clinically debatable.”

In an interview, oncologist-gynecologist George Saade, MD, of the University of Texas Medical Branch, Galveston, noted that “oxytocin is frequently used for either induction or augmentation of labor ... with the goal of improving maternal and neonatal outcomes.”

Oxytocin itself is not expensive, Dr. Saade said. “However, when it is given, the patient requires more monitoring, which may increase cost.”

There’s debate over the proper use of oxytocin, which is available in a synthetic version as Pitocin, and researchers have been trying to understand whether it can safely be discontinued early in labor.

Potential side effects of oxytocin include heart disorders such as arrhythmia, asphyxia, neonatal seizure, and jaundice, low Apgar score, and fetal death. A boxed warning says: “Because the available data are inadequate to evaluate the benefits-to-risks considerations, oxytocin is not indicated for elective induction of labor.”

However, “overall oxytocin is commonly used and very safe as long as careful protocols are followed,” David N. Hackney, MD, MS, of University Hospitals Cleveland, said in an interview. “The medication itself does not have many negative side effects. With very high doses there can be a concern for water intoxication, though this is clinically very uncommon. Some prior studies have raised concerns about the use of oxytocin and subsequent long-term neurodevelopmental outcomes, though these associations are likely confounders and the mainstream opinion is that these are not truly biologically causative associations.”

A 2021 study in The BMJ randomly assigned 1,200 women to continue or discontinue oxytocin. There was a slight increase in cesarean sections in the discontinuation group but significantly lower risks of uterine hyperstimulation and abnormal fetal heart rate.

Dr. Hackney, who didn’t take part in the new study, said the trial is “well conducted and well executed.” However, it needs peer review before any of its findings should change practice.

He added that differences in delivery protocols between the United States and France should be considered. As he noted, Dr. Girault mentioned in a Q&A after her presentation that delayed second-stage labor is more common in France than in the United States.

The study was funded by the French National Ministry of Health. Disclosures for the authors were not provided. Dr. Saade and Dr. Hackney have no disclosures.

A new randomized, open-label French trial offers more evidence that the discontinuation of oxytocin treatment after the earliest stages of labor may be safe. Stopping oxytocin didn’t appear to affect neonatal outcomes, compared with continual use of the medication. However, the first stage of labor lasted slightly longer – not surprisingly – in those in the intervention group, and many of those who stopped oxytocin treatment resumed it later.

“Our trial did not show any impact of oxytocin discontinuation in the active [labor] stage on neonatal morbidity cesarean delivery, postpartum hemorrhage, birth experience, and postpartum depression,” said Aude Girault, MD, PhD, of Paris Cité University, in a presentation in San Francisco at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The goal of the STOPOXY study is to build upon previous research that found oxytocin discontinuation didn’t boost the risk of cesarean delivery rates, uterine hyperstimulation, and abnormal fetal heart rate, Dr. Girault said. “These studies were underpowered to show any effects on neonatal morbidity,” so she and colleagues decided to dig deeper into the issue by launching the new trial.

From 2020 to 2022, researchers assigned 2,367 women who received oxytocin before 4 centimeters dilation to either continue with the drug (n = 1,192) or discontinue it before reaching 6 centimeters dilation (n = 1,175). Overall, the women were pregnant for the first time (around 55%) with a median age around 32 years and body mass index around 24.1 kg/m². All had live, singleton, full-term babies.

More than a third – 37% – of those who discontinued oxytocin resumed treatment with the medication, while 5% of those in the control group stopped taking it.

The neonatal morbidity rate – defined via a composite variable based on umbilical arterial pH, umbilical arterial lactates, Apgar score, and/or neonatal ICU admission – was 10.0% in the intervention group and 10.1% in the control group (P = .94), the researchers reported. Cesarean delivery rates were similar (18.8% vs. 16.5%, respectively; P = .22). Apart from the duration of the active first stage, which was significantly higher in the intervention group (100 min [ interquartile range, 50-208 min] vs. 90 min [IQR, 45-150 min]; P = .001), there were no significant differences between the groups.

Dr. Girault said this increase in labor duration was “moderate and clinically debatable.”

In an interview, oncologist-gynecologist George Saade, MD, of the University of Texas Medical Branch, Galveston, noted that “oxytocin is frequently used for either induction or augmentation of labor ... with the goal of improving maternal and neonatal outcomes.”

Oxytocin itself is not expensive, Dr. Saade said. “However, when it is given, the patient requires more monitoring, which may increase cost.”

There’s debate over the proper use of oxytocin, which is available in a synthetic version as Pitocin, and researchers have been trying to understand whether it can safely be discontinued early in labor.

Potential side effects of oxytocin include heart disorders such as arrhythmia, asphyxia, neonatal seizure, and jaundice, low Apgar score, and fetal death. A boxed warning says: “Because the available data are inadequate to evaluate the benefits-to-risks considerations, oxytocin is not indicated for elective induction of labor.”

However, “overall oxytocin is commonly used and very safe as long as careful protocols are followed,” David N. Hackney, MD, MS, of University Hospitals Cleveland, said in an interview. “The medication itself does not have many negative side effects. With very high doses there can be a concern for water intoxication, though this is clinically very uncommon. Some prior studies have raised concerns about the use of oxytocin and subsequent long-term neurodevelopmental outcomes, though these associations are likely confounders and the mainstream opinion is that these are not truly biologically causative associations.”

A 2021 study in The BMJ randomly assigned 1,200 women to continue or discontinue oxytocin. There was a slight increase in cesarean sections in the discontinuation group but significantly lower risks of uterine hyperstimulation and abnormal fetal heart rate.

Dr. Hackney, who didn’t take part in the new study, said the trial is “well conducted and well executed.” However, it needs peer review before any of its findings should change practice.

He added that differences in delivery protocols between the United States and France should be considered. As he noted, Dr. Girault mentioned in a Q&A after her presentation that delayed second-stage labor is more common in France than in the United States.

The study was funded by the French National Ministry of Health. Disclosures for the authors were not provided. Dr. Saade and Dr. Hackney have no disclosures.

A 27-gene immuno-oncology assay appears to provide useful information about whether patients with advanced non–small cell lung cancer (NSCLC) could benefit from immune checkpoint inhibitor (ICI) therapy despite their poor status, researchers reported.

Positive findings on the test, known as DetermaIO, were “associated with efficacy of response to ICI therapy in advanced NSCLC patients,” Matthew G. Varga, PhD, manager of scientific affairs at Oncocyte, said in an interview. “These data suggest that DetermaIO warrants further study in poor performance status patients as it has the potential to identify likely responders to ICI therapy.”

Oncocyte, which is developing the test, presented the findings in a poster at the annual meeting of the Society for Immunotherapy of Cancer.

According to Dr. Varga, “DetermaIO is an RT-qPCR test that can be applied to FFPE [formalin-fixed, paraffin-embedded] tissue specimens to quantify the relative gene expression of 27 genes and subsequently applies our proprietary algorithm to generate an IO score based on the gene expression profile. The DetermaIO score is a binary IO+ or IO– score, representing likely responder or nonresponder, respectively.”

The test was originally developed for triple negative breast cancer, Dr. Varga said, and it’s been validated in non–small cell lung cancer, metastatic urothelial carcinoma, and metastatic colorectal carcinoma.

For the study, the researchers retrospectively tracked associations between DetermaIO score and either progression-free survival (PFS) or overall survival (OS) in 147 patients in Canada with NSCLC who were treated with ICI monotherapy. All had programmed death-ligand 1 (PD-L1) ≥ 50%.

Overall, outcomes were poor: The median survival was 12.7 months, and median PFS was 7.0 months. These outcomes were even worse in those who underwent therapy as a second- line treatment: The median survival was 9.7 months, and median PFS was 4.4 months.

“DetermaIO was significantly associated with PFS at hazard ratio [HR] = 0.55, 95% [confidence interval] CI, 0.32-0.94, P = .028. In our analyses, a hazard ratio less than 1 suggests lower risk – i.e, that DetermaIO+ patients have lower risk of an event – death or progression – compared to a DetermaIO– patient,” Dr. Varga said. “The association for overall survival was not statistically significant, but it was suggestive of clinically meaningful benefit.”

He added that “we could identify likely responders from nonresponders, suggesting that the DetermaIO score adds both independent and incremental data to the existing gold standard biomarker. The objective response rate for all first-line patients – n = 78 – was 44.9%. Twenty-two DetermaIO– tumors had a 23% response rate (5 partial responses) whereas of the 56 DetermaIO+ patients, the response rate was 54% (2 complete response and 28 partial responses).”

A score on the test, he said, was not associated with OS or PFS in patients who received second-line or later treatment.

The study was not designed to evaluate the predictive power of the test. “For a biomarker to be defined as predictive requires a formal test of interaction between a treatment group (ICI monotherapy, for example) vs. a control group (chemo-only or other regimen),” Dr. Varga explained. “In our analysis, there was no group of patients who did not receive ICI monotherapy. Thus a test for interaction and a predictive claim cannot be made.”

The test is available for at no cost via an early access program, Dr. Varga said, and Oncocyte is getting ready to seek Medicare coverage. The ultimate cost of the test, he said, is unknown.

Oncocyte funded this study. Dr. Varga and several other study authors are Oncocyte employees, and another author is a paid consultant to the company.

A 27-gene immuno-oncology assay appears to provide useful information about whether patients with advanced non–small cell lung cancer (NSCLC) could benefit from immune checkpoint inhibitor (ICI) therapy despite their poor status, researchers reported.

Positive findings on the test, known as DetermaIO, were “associated with efficacy of response to ICI therapy in advanced NSCLC patients,” Matthew G. Varga, PhD, manager of scientific affairs at Oncocyte, said in an interview. “These data suggest that DetermaIO warrants further study in poor performance status patients as it has the potential to identify likely responders to ICI therapy.”

Oncocyte, which is developing the test, presented the findings in a poster at the annual meeting of the Society for Immunotherapy of Cancer.

According to Dr. Varga, “DetermaIO is an RT-qPCR test that can be applied to FFPE [formalin-fixed, paraffin-embedded] tissue specimens to quantify the relative gene expression of 27 genes and subsequently applies our proprietary algorithm to generate an IO score based on the gene expression profile. The DetermaIO score is a binary IO+ or IO– score, representing likely responder or nonresponder, respectively.”

The test was originally developed for triple negative breast cancer, Dr. Varga said, and it’s been validated in non–small cell lung cancer, metastatic urothelial carcinoma, and metastatic colorectal carcinoma.

For the study, the researchers retrospectively tracked associations between DetermaIO score and either progression-free survival (PFS) or overall survival (OS) in 147 patients in Canada with NSCLC who were treated with ICI monotherapy. All had programmed death-ligand 1 (PD-L1) ≥ 50%.

Overall, outcomes were poor: The median survival was 12.7 months, and median PFS was 7.0 months. These outcomes were even worse in those who underwent therapy as a second- line treatment: The median survival was 9.7 months, and median PFS was 4.4 months.

“DetermaIO was significantly associated with PFS at hazard ratio [HR] = 0.55, 95% [confidence interval] CI, 0.32-0.94, P = .028. In our analyses, a hazard ratio less than 1 suggests lower risk – i.e, that DetermaIO+ patients have lower risk of an event – death or progression – compared to a DetermaIO– patient,” Dr. Varga said. “The association for overall survival was not statistically significant, but it was suggestive of clinically meaningful benefit.”

He added that “we could identify likely responders from nonresponders, suggesting that the DetermaIO score adds both independent and incremental data to the existing gold standard biomarker. The objective response rate for all first-line patients – n = 78 – was 44.9%. Twenty-two DetermaIO– tumors had a 23% response rate (5 partial responses) whereas of the 56 DetermaIO+ patients, the response rate was 54% (2 complete response and 28 partial responses).”

A score on the test, he said, was not associated with OS or PFS in patients who received second-line or later treatment.

The study was not designed to evaluate the predictive power of the test. “For a biomarker to be defined as predictive requires a formal test of interaction between a treatment group (ICI monotherapy, for example) vs. a control group (chemo-only or other regimen),” Dr. Varga explained. “In our analysis, there was no group of patients who did not receive ICI monotherapy. Thus a test for interaction and a predictive claim cannot be made.”

The test is available for at no cost via an early access program, Dr. Varga said, and Oncocyte is getting ready to seek Medicare coverage. The ultimate cost of the test, he said, is unknown.

Oncocyte funded this study. Dr. Varga and several other study authors are Oncocyte employees, and another author is a paid consultant to the company.

A 27-gene immuno-oncology assay appears to provide useful information about whether patients with advanced non–small cell lung cancer (NSCLC) could benefit from immune checkpoint inhibitor (ICI) therapy despite their poor status, researchers reported.

Positive findings on the test, known as DetermaIO, were “associated with efficacy of response to ICI therapy in advanced NSCLC patients,” Matthew G. Varga, PhD, manager of scientific affairs at Oncocyte, said in an interview. “These data suggest that DetermaIO warrants further study in poor performance status patients as it has the potential to identify likely responders to ICI therapy.”

Oncocyte, which is developing the test, presented the findings in a poster at the annual meeting of the Society for Immunotherapy of Cancer.

According to Dr. Varga, “DetermaIO is an RT-qPCR test that can be applied to FFPE [formalin-fixed, paraffin-embedded] tissue specimens to quantify the relative gene expression of 27 genes and subsequently applies our proprietary algorithm to generate an IO score based on the gene expression profile. The DetermaIO score is a binary IO+ or IO– score, representing likely responder or nonresponder, respectively.”

The test was originally developed for triple negative breast cancer, Dr. Varga said, and it’s been validated in non–small cell lung cancer, metastatic urothelial carcinoma, and metastatic colorectal carcinoma.

For the study, the researchers retrospectively tracked associations between DetermaIO score and either progression-free survival (PFS) or overall survival (OS) in 147 patients in Canada with NSCLC who were treated with ICI monotherapy. All had programmed death-ligand 1 (PD-L1) ≥ 50%.

Overall, outcomes were poor: The median survival was 12.7 months, and median PFS was 7.0 months. These outcomes were even worse in those who underwent therapy as a second- line treatment: The median survival was 9.7 months, and median PFS was 4.4 months.

“DetermaIO was significantly associated with PFS at hazard ratio [HR] = 0.55, 95% [confidence interval] CI, 0.32-0.94, P = .028. In our analyses, a hazard ratio less than 1 suggests lower risk – i.e, that DetermaIO+ patients have lower risk of an event – death or progression – compared to a DetermaIO– patient,” Dr. Varga said. “The association for overall survival was not statistically significant, but it was suggestive of clinically meaningful benefit.”

He added that “we could identify likely responders from nonresponders, suggesting that the DetermaIO score adds both independent and incremental data to the existing gold standard biomarker. The objective response rate for all first-line patients – n = 78 – was 44.9%. Twenty-two DetermaIO– tumors had a 23% response rate (5 partial responses) whereas of the 56 DetermaIO+ patients, the response rate was 54% (2 complete response and 28 partial responses).”

A score on the test, he said, was not associated with OS or PFS in patients who received second-line or later treatment.

The study was not designed to evaluate the predictive power of the test. “For a biomarker to be defined as predictive requires a formal test of interaction between a treatment group (ICI monotherapy, for example) vs. a control group (chemo-only or other regimen),” Dr. Varga explained. “In our analysis, there was no group of patients who did not receive ICI monotherapy. Thus a test for interaction and a predictive claim cannot be made.”

The test is available for at no cost via an early access program, Dr. Varga said, and Oncocyte is getting ready to seek Medicare coverage. The ultimate cost of the test, he said, is unknown.

Oncocyte funded this study. Dr. Varga and several other study authors are Oncocyte employees, and another author is a paid consultant to the company.

Long-course radiation therapy for rectal cancer is more likely to spare organs than short-course therapy, including when chemotherapy is provided first as part of a total neoadjuvant therapy (TNT) strategy, shows new research presented at the ASCO Gastrointestinal Cancers Symposium 2023.

“When we looked at the 2-year organ preservation rates, they were numerically higher in the long-course group versus the short-course group,” said study author J. Joshua Smith, MD, PhD,FACS, a colorectal surgeon with Memorial Sloan Kettering Cancer Center, New York. “Our study will be the first, to our knowledge, that examines a significant proportion of patients treated with the induction total neoadjuvant therapy approach – chemo first.”

An ideal outcome in rectal cancer is no need for surgery, Dr. Smith said. “If you can avoid surgery altogether and preserve the organ [the rectum], that’s a big win for the patient as they are usually able to avoid having a permanent or temporary ostomy.”

Long-course and short-course radiation have similar outcomes in terms of patients going on to need surgery, but it’s not clear which is superior in terms of organ sparing, toxicity, and side effects, said Paul Romesser, MD, a radiation oncologist with Memorial Sloan Kettering Cancer Center, New York, who served as first author of the study.

During the early months of the COVID-19 pandemic, the cancer center embraced short-course radiation in rectal cancer, Dr. Romesser said. “Once we emerged from the cloud of COVID, we said: ‘Well, what do we do now? Where do we go? Do we go back to what we did before? Or, do we go stick with the same? And what does that mean for organ preservation?’ ”

The researchers retrospectively identified 563 consecutive patients treated with TNT from 2018 to 2021. They focused on 332 who didn’t have metastatic disease, synchronous/metachronous malignancies, or nonadenocarcinoma histology (long course = 256, short course = 76). The groups had similar high-risk features, and about 82% were clinical stage III).

Patients most commonly received induction chemotherapy followed by consolidative radiation (78% long course, 70% short course).

The 2-year survival rates were similar, but organ preservation was higher in the long-course group versus the short-course group (40%; 95% confidence interval, 35%-47% vs. 29%; 95% CI, 20%-42%). And the 2-year local regrowth rate was also better in the long-course group versus the short-course group (20%; 95% CI, 12%-27% vs. 36%; 95% CI, 16%-52%).

Why might long-course therapy be better? “It’s probably just coming down to the biologically equivalent dose,” which is likely lower in short-course radiation, Dr. Romesser said.

Going forward, Dr. Romesser said he’ll tell patients about the findings of this study and a previous report published in 2022 that determined that “organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME [total mesorectal excision], and postoperative chemotherapy.” Dr. Smith is a coauthor of that study.

“Generally, I’ll steer patients toward long course, assuming all else is equal, and it’s not an undue burden on them financially and socially to come in for 5-6 weeks of chemoradiation,” Dr. Romesser said. He added that, “generally, the insurance companies recognize [short-course and long-course radiation] as both acceptable and standard treatment options for patients. We haven’t found that insurances will approve one, but not the other.”

The study was funded by the National Institutes of Health. Dr. Romesser disclosed consulting/advisory roles (EMD Serono, Faeth, Natera), research funding (XRad), and travel/accommodations/expenses (Elekta). Dr. Smith disclosed consulting/advisory roles (Foundation Medicine, Guardant Health). The other study authors reported no conflicts of interest.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Long-course radiation therapy for rectal cancer is more likely to spare organs than short-course therapy, including when chemotherapy is provided first as part of a total neoadjuvant therapy (TNT) strategy, shows new research presented at the ASCO Gastrointestinal Cancers Symposium 2023.

“When we looked at the 2-year organ preservation rates, they were numerically higher in the long-course group versus the short-course group,” said study author J. Joshua Smith, MD, PhD,FACS, a colorectal surgeon with Memorial Sloan Kettering Cancer Center, New York. “Our study will be the first, to our knowledge, that examines a significant proportion of patients treated with the induction total neoadjuvant therapy approach – chemo first.”

An ideal outcome in rectal cancer is no need for surgery, Dr. Smith said. “If you can avoid surgery altogether and preserve the organ [the rectum], that’s a big win for the patient as they are usually able to avoid having a permanent or temporary ostomy.”

Long-course and short-course radiation have similar outcomes in terms of patients going on to need surgery, but it’s not clear which is superior in terms of organ sparing, toxicity, and side effects, said Paul Romesser, MD, a radiation oncologist with Memorial Sloan Kettering Cancer Center, New York, who served as first author of the study.

During the early months of the COVID-19 pandemic, the cancer center embraced short-course radiation in rectal cancer, Dr. Romesser said. “Once we emerged from the cloud of COVID, we said: ‘Well, what do we do now? Where do we go? Do we go back to what we did before? Or, do we go stick with the same? And what does that mean for organ preservation?’ ”

The researchers retrospectively identified 563 consecutive patients treated with TNT from 2018 to 2021. They focused on 332 who didn’t have metastatic disease, synchronous/metachronous malignancies, or nonadenocarcinoma histology (long course = 256, short course = 76). The groups had similar high-risk features, and about 82% were clinical stage III).

Patients most commonly received induction chemotherapy followed by consolidative radiation (78% long course, 70% short course).

The 2-year survival rates were similar, but organ preservation was higher in the long-course group versus the short-course group (40%; 95% confidence interval, 35%-47% vs. 29%; 95% CI, 20%-42%). And the 2-year local regrowth rate was also better in the long-course group versus the short-course group (20%; 95% CI, 12%-27% vs. 36%; 95% CI, 16%-52%).

Why might long-course therapy be better? “It’s probably just coming down to the biologically equivalent dose,” which is likely lower in short-course radiation, Dr. Romesser said.

Going forward, Dr. Romesser said he’ll tell patients about the findings of this study and a previous report published in 2022 that determined that “organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME [total mesorectal excision], and postoperative chemotherapy.” Dr. Smith is a coauthor of that study.

“Generally, I’ll steer patients toward long course, assuming all else is equal, and it’s not an undue burden on them financially and socially to come in for 5-6 weeks of chemoradiation,” Dr. Romesser said. He added that, “generally, the insurance companies recognize [short-course and long-course radiation] as both acceptable and standard treatment options for patients. We haven’t found that insurances will approve one, but not the other.”

The study was funded by the National Institutes of Health. Dr. Romesser disclosed consulting/advisory roles (EMD Serono, Faeth, Natera), research funding (XRad), and travel/accommodations/expenses (Elekta). Dr. Smith disclosed consulting/advisory roles (Foundation Medicine, Guardant Health). The other study authors reported no conflicts of interest.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Long-course radiation therapy for rectal cancer is more likely to spare organs than short-course therapy, including when chemotherapy is provided first as part of a total neoadjuvant therapy (TNT) strategy, shows new research presented at the ASCO Gastrointestinal Cancers Symposium 2023.

“When we looked at the 2-year organ preservation rates, they were numerically higher in the long-course group versus the short-course group,” said study author J. Joshua Smith, MD, PhD,FACS, a colorectal surgeon with Memorial Sloan Kettering Cancer Center, New York. “Our study will be the first, to our knowledge, that examines a significant proportion of patients treated with the induction total neoadjuvant therapy approach – chemo first.”

An ideal outcome in rectal cancer is no need for surgery, Dr. Smith said. “If you can avoid surgery altogether and preserve the organ [the rectum], that’s a big win for the patient as they are usually able to avoid having a permanent or temporary ostomy.”

Long-course and short-course radiation have similar outcomes in terms of patients going on to need surgery, but it’s not clear which is superior in terms of organ sparing, toxicity, and side effects, said Paul Romesser, MD, a radiation oncologist with Memorial Sloan Kettering Cancer Center, New York, who served as first author of the study.

During the early months of the COVID-19 pandemic, the cancer center embraced short-course radiation in rectal cancer, Dr. Romesser said. “Once we emerged from the cloud of COVID, we said: ‘Well, what do we do now? Where do we go? Do we go back to what we did before? Or, do we go stick with the same? And what does that mean for organ preservation?’ ”

The researchers retrospectively identified 563 consecutive patients treated with TNT from 2018 to 2021. They focused on 332 who didn’t have metastatic disease, synchronous/metachronous malignancies, or nonadenocarcinoma histology (long course = 256, short course = 76). The groups had similar high-risk features, and about 82% were clinical stage III).

Patients most commonly received induction chemotherapy followed by consolidative radiation (78% long course, 70% short course).

The 2-year survival rates were similar, but organ preservation was higher in the long-course group versus the short-course group (40%; 95% confidence interval, 35%-47% vs. 29%; 95% CI, 20%-42%). And the 2-year local regrowth rate was also better in the long-course group versus the short-course group (20%; 95% CI, 12%-27% vs. 36%; 95% CI, 16%-52%).

Why might long-course therapy be better? “It’s probably just coming down to the biologically equivalent dose,” which is likely lower in short-course radiation, Dr. Romesser said.

Going forward, Dr. Romesser said he’ll tell patients about the findings of this study and a previous report published in 2022 that determined that “organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME [total mesorectal excision], and postoperative chemotherapy.” Dr. Smith is a coauthor of that study.

“Generally, I’ll steer patients toward long course, assuming all else is equal, and it’s not an undue burden on them financially and socially to come in for 5-6 weeks of chemoradiation,” Dr. Romesser said. He added that, “generally, the insurance companies recognize [short-course and long-course radiation] as both acceptable and standard treatment options for patients. We haven’t found that insurances will approve one, but not the other.”

The study was funded by the National Institutes of Health. Dr. Romesser disclosed consulting/advisory roles (EMD Serono, Faeth, Natera), research funding (XRad), and travel/accommodations/expenses (Elekta). Dr. Smith disclosed consulting/advisory roles (Foundation Medicine, Guardant Health). The other study authors reported no conflicts of interest.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Antibiotic use doesn’t appear to disrupt the effectiveness of the immune checkpoint inhibitor durvalumab in advanced biliary tract cancer, according to a new analysis of the landmark TOPAZ-1 clinical trial.

The findings, released at the ASCO Gastrointestinal Cancers Symposium 2023, suggest that “people with advanced biliary tract cancer can safely be treated with antibiotics while still benefiting from treatment with durvalumab plus chemotherapy,” said lead author Aiwu Ruth He, MD, PhD, a gastrointestinal oncologist with MedStar Georgetown University Hospital, Washington.

Antibiotic use during immune checkpoint inhibitor therapy has been associated with poorer outcomes. A review of 12 studies published in Frontiers in Oncology found that antibiotic use was associated with worse progression-free and overall survival.

“Patients with biliary tract cancer have the increased risk of biliary tract infection as the result of biliary tract obstruction, and they often receive antibiotics,” Dr. He said.

A 2020 report in eCancer suggested that antibiotics may disrupt gut bacteria and, as a result, interfere with the immune system’s responsiveness. “It has been a consensus that the use of broad-spectrum antibiotics should be avoided during the use of immunotherapy whenever possible,” the report authors wrote. “In addition, antibiotics should be prescribed only when properly indicated.”

However, cutting down on antibiotic use may be especially difficult in cancer patients since they frequently suffer from infections. “An antibiotic-resistant bacterial infection may cause serious issues for a cancer patient, who likely already has a suppressed immune system,” according to a 2017 information sheet posted by the Cancer Treatment Centers of America. “Chemotherapy may cause neutropenia, a reduction of white blood cells that help fight infections and viruses. Radiation therapy may damage the skin and cause irritation and wounds. Immunotherapy or targeted therapy drugs may trigger side effects that may lead to infections. Incisions from surgery or to insert ports or catheters may be vulnerable to infections.”

The new study

For the new subgroup analysis, researchers analyzed data from the phase 3 TOPAZ-1 clinical trial, which was a double-blinded analysis of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. The previously reported main findings from the study were positive with a median overall survival of 12.8 months in the durvalumab arm versus 11.5 months in the placebo arm (hazard ratio, 0.80; P = .021). These findings contributed to the Food and Drug Administration’s decision in 2022 to approve the treatment for use in locally advanced or metastatic biliary tract cancer.

Of 341 patients who received durvalumab treatment, 167 also took antibiotics. The median overall survival in the antibiotic and nonantibiotic groups were similar at 12.6 months (95% confidence interval, 9.7-14.8 months) and 13 months (95% CI, 10.8-14.7 months), respectively. Median progression-free survival was 7.3 months (95% CI, 6.5-7.7 months) and 7.2 months (95% CI, 5.9-7.4 months), respectively.

“The results support that advanced patients’ risk of death, and the risk that their cancer would grow, spread, or get worse, was not meaningfully different between patients who used antibiotics and those who did not use antibiotics at the same time as they were receiving durvalumab-based treatment,” Dr. He said. “The result is not surprising to me since it is not clear to me how and why antibiotics may affect the effectiveness of immunotherapy.”

Moving forward, she said, “additional studies are needed to further investigator the relationship between antibiotics use and effectiveness of immunotherapy. We need to understand why use of antibiotics during treatment with immunotherapy is correlated with poor outcomes in some circumstances but not in other circumstances.”

The study was funded by AstraZeneca. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Antibiotic use doesn’t appear to disrupt the effectiveness of the immune checkpoint inhibitor durvalumab in advanced biliary tract cancer, according to a new analysis of the landmark TOPAZ-1 clinical trial.

The findings, released at the ASCO Gastrointestinal Cancers Symposium 2023, suggest that “people with advanced biliary tract cancer can safely be treated with antibiotics while still benefiting from treatment with durvalumab plus chemotherapy,” said lead author Aiwu Ruth He, MD, PhD, a gastrointestinal oncologist with MedStar Georgetown University Hospital, Washington.

Antibiotic use during immune checkpoint inhibitor therapy has been associated with poorer outcomes. A review of 12 studies published in Frontiers in Oncology found that antibiotic use was associated with worse progression-free and overall survival.

“Patients with biliary tract cancer have the increased risk of biliary tract infection as the result of biliary tract obstruction, and they often receive antibiotics,” Dr. He said.

A 2020 report in eCancer suggested that antibiotics may disrupt gut bacteria and, as a result, interfere with the immune system’s responsiveness. “It has been a consensus that the use of broad-spectrum antibiotics should be avoided during the use of immunotherapy whenever possible,” the report authors wrote. “In addition, antibiotics should be prescribed only when properly indicated.”

However, cutting down on antibiotic use may be especially difficult in cancer patients since they frequently suffer from infections. “An antibiotic-resistant bacterial infection may cause serious issues for a cancer patient, who likely already has a suppressed immune system,” according to a 2017 information sheet posted by the Cancer Treatment Centers of America. “Chemotherapy may cause neutropenia, a reduction of white blood cells that help fight infections and viruses. Radiation therapy may damage the skin and cause irritation and wounds. Immunotherapy or targeted therapy drugs may trigger side effects that may lead to infections. Incisions from surgery or to insert ports or catheters may be vulnerable to infections.”

The new study

For the new subgroup analysis, researchers analyzed data from the phase 3 TOPAZ-1 clinical trial, which was a double-blinded analysis of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. The previously reported main findings from the study were positive with a median overall survival of 12.8 months in the durvalumab arm versus 11.5 months in the placebo arm (hazard ratio, 0.80; P = .021). These findings contributed to the Food and Drug Administration’s decision in 2022 to approve the treatment for use in locally advanced or metastatic biliary tract cancer.

Of 341 patients who received durvalumab treatment, 167 also took antibiotics. The median overall survival in the antibiotic and nonantibiotic groups were similar at 12.6 months (95% confidence interval, 9.7-14.8 months) and 13 months (95% CI, 10.8-14.7 months), respectively. Median progression-free survival was 7.3 months (95% CI, 6.5-7.7 months) and 7.2 months (95% CI, 5.9-7.4 months), respectively.

“The results support that advanced patients’ risk of death, and the risk that their cancer would grow, spread, or get worse, was not meaningfully different between patients who used antibiotics and those who did not use antibiotics at the same time as they were receiving durvalumab-based treatment,” Dr. He said. “The result is not surprising to me since it is not clear to me how and why antibiotics may affect the effectiveness of immunotherapy.”

Moving forward, she said, “additional studies are needed to further investigator the relationship between antibiotics use and effectiveness of immunotherapy. We need to understand why use of antibiotics during treatment with immunotherapy is correlated with poor outcomes in some circumstances but not in other circumstances.”

The study was funded by AstraZeneca. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Antibiotic use doesn’t appear to disrupt the effectiveness of the immune checkpoint inhibitor durvalumab in advanced biliary tract cancer, according to a new analysis of the landmark TOPAZ-1 clinical trial.

The findings, released at the ASCO Gastrointestinal Cancers Symposium 2023, suggest that “people with advanced biliary tract cancer can safely be treated with antibiotics while still benefiting from treatment with durvalumab plus chemotherapy,” said lead author Aiwu Ruth He, MD, PhD, a gastrointestinal oncologist with MedStar Georgetown University Hospital, Washington.

Antibiotic use during immune checkpoint inhibitor therapy has been associated with poorer outcomes. A review of 12 studies published in Frontiers in Oncology found that antibiotic use was associated with worse progression-free and overall survival.

“Patients with biliary tract cancer have the increased risk of biliary tract infection as the result of biliary tract obstruction, and they often receive antibiotics,” Dr. He said.

A 2020 report in eCancer suggested that antibiotics may disrupt gut bacteria and, as a result, interfere with the immune system’s responsiveness. “It has been a consensus that the use of broad-spectrum antibiotics should be avoided during the use of immunotherapy whenever possible,” the report authors wrote. “In addition, antibiotics should be prescribed only when properly indicated.”

However, cutting down on antibiotic use may be especially difficult in cancer patients since they frequently suffer from infections. “An antibiotic-resistant bacterial infection may cause serious issues for a cancer patient, who likely already has a suppressed immune system,” according to a 2017 information sheet posted by the Cancer Treatment Centers of America. “Chemotherapy may cause neutropenia, a reduction of white blood cells that help fight infections and viruses. Radiation therapy may damage the skin and cause irritation and wounds. Immunotherapy or targeted therapy drugs may trigger side effects that may lead to infections. Incisions from surgery or to insert ports or catheters may be vulnerable to infections.”

The new study

For the new subgroup analysis, researchers analyzed data from the phase 3 TOPAZ-1 clinical trial, which was a double-blinded analysis of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. The previously reported main findings from the study were positive with a median overall survival of 12.8 months in the durvalumab arm versus 11.5 months in the placebo arm (hazard ratio, 0.80; P = .021). These findings contributed to the Food and Drug Administration’s decision in 2022 to approve the treatment for use in locally advanced or metastatic biliary tract cancer.

Of 341 patients who received durvalumab treatment, 167 also took antibiotics. The median overall survival in the antibiotic and nonantibiotic groups were similar at 12.6 months (95% confidence interval, 9.7-14.8 months) and 13 months (95% CI, 10.8-14.7 months), respectively. Median progression-free survival was 7.3 months (95% CI, 6.5-7.7 months) and 7.2 months (95% CI, 5.9-7.4 months), respectively.

“The results support that advanced patients’ risk of death, and the risk that their cancer would grow, spread, or get worse, was not meaningfully different between patients who used antibiotics and those who did not use antibiotics at the same time as they were receiving durvalumab-based treatment,” Dr. He said. “The result is not surprising to me since it is not clear to me how and why antibiotics may affect the effectiveness of immunotherapy.”

Moving forward, she said, “additional studies are needed to further investigator the relationship between antibiotics use and effectiveness of immunotherapy. We need to understand why use of antibiotics during treatment with immunotherapy is correlated with poor outcomes in some circumstances but not in other circumstances.”

The study was funded by AstraZeneca. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

While it’s well known that COVID-19 vaccines are less effective in patients with chronic lymphocytic leukemia (CLL) who take immunity-lowering drugs, a new study offers fresh insight into what’s happening inside the body. In these patients, the vaccines often don’t boost B cells, which produce antibodies, but they do strengthen T cells, potentially providing crucial protection against severe illness and death.

These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.

“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.

Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.

“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.

Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”

The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.

The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.

By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.

The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.

Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.

The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.

Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.

In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”

Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”

As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”

The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.

While it’s well known that COVID-19 vaccines are less effective in patients with chronic lymphocytic leukemia (CLL) who take immunity-lowering drugs, a new study offers fresh insight into what’s happening inside the body. In these patients, the vaccines often don’t boost B cells, which produce antibodies, but they do strengthen T cells, potentially providing crucial protection against severe illness and death.

These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.

“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.

Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.

“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.

Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”

The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.

The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.

By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.

The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.

Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.

The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.

Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.

In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”

Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”

As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”

The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.

While it’s well known that COVID-19 vaccines are less effective in patients with chronic lymphocytic leukemia (CLL) who take immunity-lowering drugs, a new study offers fresh insight into what’s happening inside the body. In these patients, the vaccines often don’t boost B cells, which produce antibodies, but they do strengthen T cells, potentially providing crucial protection against severe illness and death.

These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.

“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.

Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.

“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.

Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”

The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.

The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.

By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.

The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.

Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.

The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.

Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.

In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”

Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”

As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”

The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.

Most patients with end-stage hepatocellular carcinoma experience pain, but when it’s severe, how best to control the pain is debatable. A number of studies, including one recently presented at the ASCO Gastrointestinal Cancers Symposium 2023, shows that low-dose radiotherapy can improve pain, and in this case, even improve survival.

The study, conducted by Laura Dawson, MD, a radiation oncologist with the Princess Margaret Cancer Center, Toronto, was conducted in 66 patients with painful hepatocellular carcinoma or liver metastases. They were randomized to receive either palliative radiotherapy (single fraction 8 gray) or standard pain control. Sixty-three percent of patients treated with radiotherapy reported significant improvements in mild pain compared with 28% of patients who received standard pain control (P = .03).

Currently, palliative radiotherapy to control pain in late stage cancer may be an option for some patients with other types of advanced cancer, but in liver cancer, there is little data to support its routine use in patients with terminal hepatocellular carcinoma. “Several prior studies have shown radiation therapy may be delivered safely and that it may help patients with hepatic cancer pain,” Dr. Dawson said. But the previous studies have mostly been single-arm, she said, and many lacked patient-reported outcomes.

In liver cancer, existing therapies are largely inadequate for pain relief, especially for moderate to severe pain. Systemic therapy isn’t effective for rapid pain relief. And, for a subset of patients with end-stage liver cancer, standard pain control with acetaminophen, steroids, and narcotics either is not effective or cannot be tolerated because of underlying cirrhosis or poor liver function due to the cancer.

Although not clinically significant, palliative radiotherapy improved 3-month survival (51%) compared with patients who received best supportive care (33%, P = .07). “Interestingly, there was a trend for improved survival in those patients who received radiation with a 3-month survival of 51% versus 33% of those who received best supportive care. Clearly, the study was not powered for this, but it is very intriguing and hopefully sets the stage for future clinical trials.”

In this study, “simple radiotherapy was used and could consist of two beams, opposed or oblique parallel pair, or simple intensity modulated radiation. This is available with any medical linear accelerator or any cancer center,” Dr. Dawson said. “A single dose of radiation therapy with an antiemetic is a low-cost simple palliative intervention for patients with analgesia-refractory hepatic pain from cancer.”
 

New data reported at ASCO GI

The Dawson et al. study included 66 patients with liver cancer who had pain scores of at least 4. They had pain that was specific to the liver and they were unsuitable for or refractory to other therapies with no other planned therapies, such as immunotherapy. Their pain was refractory to standard treatments. Of the patients, 43 had liver metastasis from cancers that originated in the colon (12), breast (5), pancreas (4), lung (3), hepatocellular carcinoma (23), or other sites (19).

At 59%, more than half of patients had ECOG performance status of 2 or 3, suggesting the cancer had progressed to the extent that they were confined to a bed or chair for more than half of their waking hours (level 3) or they were capable of self-care but unable to work (level 2). Of the 66 patients, 42 patients completed 1-month assessments and of these, 67% of 24 patients receiving palliative radiotherapy (21% had no increase in opioids) and 22% of 18 patients receiving best supportive care (with no increase in opioids) reported improvements in their worst pain levels.

The primary endpoint – the proportion of patients with a clinically important improvement in pain 1 month after therapy – was met. “There was a significant improvement in all pain endpoints from baseline to one month, with more patients who received radiotherapy reporting clinically important reduction of pain (a reduction by 2 or more on the 0 to 10 scale). The primary endpoint was pain – worst pain, and 67% of those patients who had radiation reported an improvement in their pain at worst in the past 24 hours versus 22% treated with best supportive care, with a P value .004,” Dr. Dawson said.

Adverse events of at least grade 2 or higher occurred 30 days after radiotherapy, affecting 58% of patients compared with 33% of patients who did not receive the treatment. Adverse events at grade 3 or higher were uncommon.

Dr. Dawson reports institutional research funding from Merck.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
 

Most patients with end-stage hepatocellular carcinoma experience pain, but when it’s severe, how best to control the pain is debatable. A number of studies, including one recently presented at the ASCO Gastrointestinal Cancers Symposium 2023, shows that low-dose radiotherapy can improve pain, and in this case, even improve survival.

The study, conducted by Laura Dawson, MD, a radiation oncologist with the Princess Margaret Cancer Center, Toronto, was conducted in 66 patients with painful hepatocellular carcinoma or liver metastases. They were randomized to receive either palliative radiotherapy (single fraction 8 gray) or standard pain control. Sixty-three percent of patients treated with radiotherapy reported significant improvements in mild pain compared with 28% of patients who received standard pain control (P = .03).

Currently, palliative radiotherapy to control pain in late stage cancer may be an option for some patients with other types of advanced cancer, but in liver cancer, there is little data to support its routine use in patients with terminal hepatocellular carcinoma. “Several prior studies have shown radiation therapy may be delivered safely and that it may help patients with hepatic cancer pain,” Dr. Dawson said. But the previous studies have mostly been single-arm, she said, and many lacked patient-reported outcomes.

In liver cancer, existing therapies are largely inadequate for pain relief, especially for moderate to severe pain. Systemic therapy isn’t effective for rapid pain relief. And, for a subset of patients with end-stage liver cancer, standard pain control with acetaminophen, steroids, and narcotics either is not effective or cannot be tolerated because of underlying cirrhosis or poor liver function due to the cancer.

Although not clinically significant, palliative radiotherapy improved 3-month survival (51%) compared with patients who received best supportive care (33%, P = .07). “Interestingly, there was a trend for improved survival in those patients who received radiation with a 3-month survival of 51% versus 33% of those who received best supportive care. Clearly, the study was not powered for this, but it is very intriguing and hopefully sets the stage for future clinical trials.”

In this study, “simple radiotherapy was used and could consist of two beams, opposed or oblique parallel pair, or simple intensity modulated radiation. This is available with any medical linear accelerator or any cancer center,” Dr. Dawson said. “A single dose of radiation therapy with an antiemetic is a low-cost simple palliative intervention for patients with analgesia-refractory hepatic pain from cancer.”
 

New data reported at ASCO GI

The Dawson et al. study included 66 patients with liver cancer who had pain scores of at least 4. They had pain that was specific to the liver and they were unsuitable for or refractory to other therapies with no other planned therapies, such as immunotherapy. Their pain was refractory to standard treatments. Of the patients, 43 had liver metastasis from cancers that originated in the colon (12), breast (5), pancreas (4), lung (3), hepatocellular carcinoma (23), or other sites (19).

At 59%, more than half of patients had ECOG performance status of 2 or 3, suggesting the cancer had progressed to the extent that they were confined to a bed or chair for more than half of their waking hours (level 3) or they were capable of self-care but unable to work (level 2). Of the 66 patients, 42 patients completed 1-month assessments and of these, 67% of 24 patients receiving palliative radiotherapy (21% had no increase in opioids) and 22% of 18 patients receiving best supportive care (with no increase in opioids) reported improvements in their worst pain levels.

The primary endpoint – the proportion of patients with a clinically important improvement in pain 1 month after therapy – was met. “There was a significant improvement in all pain endpoints from baseline to one month, with more patients who received radiotherapy reporting clinically important reduction of pain (a reduction by 2 or more on the 0 to 10 scale). The primary endpoint was pain – worst pain, and 67% of those patients who had radiation reported an improvement in their pain at worst in the past 24 hours versus 22% treated with best supportive care, with a P value .004,” Dr. Dawson said.

Adverse events of at least grade 2 or higher occurred 30 days after radiotherapy, affecting 58% of patients compared with 33% of patients who did not receive the treatment. Adverse events at grade 3 or higher were uncommon.

Dr. Dawson reports institutional research funding from Merck.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
 

Most patients with end-stage hepatocellular carcinoma experience pain, but when it’s severe, how best to control the pain is debatable. A number of studies, including one recently presented at the ASCO Gastrointestinal Cancers Symposium 2023, shows that low-dose radiotherapy can improve pain, and in this case, even improve survival.

The study, conducted by Laura Dawson, MD, a radiation oncologist with the Princess Margaret Cancer Center, Toronto, was conducted in 66 patients with painful hepatocellular carcinoma or liver metastases. They were randomized to receive either palliative radiotherapy (single fraction 8 gray) or standard pain control. Sixty-three percent of patients treated with radiotherapy reported significant improvements in mild pain compared with 28% of patients who received standard pain control (P = .03).

Currently, palliative radiotherapy to control pain in late stage cancer may be an option for some patients with other types of advanced cancer, but in liver cancer, there is little data to support its routine use in patients with terminal hepatocellular carcinoma. “Several prior studies have shown radiation therapy may be delivered safely and that it may help patients with hepatic cancer pain,” Dr. Dawson said. But the previous studies have mostly been single-arm, she said, and many lacked patient-reported outcomes.

In liver cancer, existing therapies are largely inadequate for pain relief, especially for moderate to severe pain. Systemic therapy isn’t effective for rapid pain relief. And, for a subset of patients with end-stage liver cancer, standard pain control with acetaminophen, steroids, and narcotics either is not effective or cannot be tolerated because of underlying cirrhosis or poor liver function due to the cancer.

Although not clinically significant, palliative radiotherapy improved 3-month survival (51%) compared with patients who received best supportive care (33%, P = .07). “Interestingly, there was a trend for improved survival in those patients who received radiation with a 3-month survival of 51% versus 33% of those who received best supportive care. Clearly, the study was not powered for this, but it is very intriguing and hopefully sets the stage for future clinical trials.”

In this study, “simple radiotherapy was used and could consist of two beams, opposed or oblique parallel pair, or simple intensity modulated radiation. This is available with any medical linear accelerator or any cancer center,” Dr. Dawson said. “A single dose of radiation therapy with an antiemetic is a low-cost simple palliative intervention for patients with analgesia-refractory hepatic pain from cancer.”
 

New data reported at ASCO GI

The Dawson et al. study included 66 patients with liver cancer who had pain scores of at least 4. They had pain that was specific to the liver and they were unsuitable for or refractory to other therapies with no other planned therapies, such as immunotherapy. Their pain was refractory to standard treatments. Of the patients, 43 had liver metastasis from cancers that originated in the colon (12), breast (5), pancreas (4), lung (3), hepatocellular carcinoma (23), or other sites (19).

At 59%, more than half of patients had ECOG performance status of 2 or 3, suggesting the cancer had progressed to the extent that they were confined to a bed or chair for more than half of their waking hours (level 3) or they were capable of self-care but unable to work (level 2). Of the 66 patients, 42 patients completed 1-month assessments and of these, 67% of 24 patients receiving palliative radiotherapy (21% had no increase in opioids) and 22% of 18 patients receiving best supportive care (with no increase in opioids) reported improvements in their worst pain levels.

The primary endpoint – the proportion of patients with a clinically important improvement in pain 1 month after therapy – was met. “There was a significant improvement in all pain endpoints from baseline to one month, with more patients who received radiotherapy reporting clinically important reduction of pain (a reduction by 2 or more on the 0 to 10 scale). The primary endpoint was pain – worst pain, and 67% of those patients who had radiation reported an improvement in their pain at worst in the past 24 hours versus 22% treated with best supportive care, with a P value .004,” Dr. Dawson said.

Adverse events of at least grade 2 or higher occurred 30 days after radiotherapy, affecting 58% of patients compared with 33% of patients who did not receive the treatment. Adverse events at grade 3 or higher were uncommon.

Dr. Dawson reports institutional research funding from Merck.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
 

Topical cannabidiol (CBD) oil appeared to lower pain scores and reduce painkiller use vs. standard treatment in patients with digital ulcers due to systemic sclerosis, a small new study finds. Patients who received the treatment also showed signs of more healing.

The study, published in Advances in Skin & Wound Care, is far from definitive since it’s retrospective and tracked only 45 patients. But the findings add to other research suggesting dermatologic benefits from the topical use of CBD, an ingredient in cannabis that’s widely available and doesn’t cause people to become high or become addicted.

Anatoliy Sizov/Getty Images

“This is a good first step in trying to address scleroderma digital ulcer pain and healing,” University of Colorado rheumatologist Melissa Griffith, MD, said in an interview. “Digital ulcers cause great impact on quality of life, daily activities of living, and pain, so we are always looking for new, effective tools.”

According to Dr. Griffith, digital ulcers occur in scleroderma due to Raynaud’s phenomenon with reversible vasospasm. “Unlike patients with primary Raynaud’s phenomenon, patients will develop ischemia of digits, leading to digital ulcers due to the vasculopathy or vascular remodeling that occurs in scleroderma,” she said.

Current treatments include removal of causative drugs/toxins and warmth, rest, and pain control, although “no trials exist to compare the scleroderma digital ulcer or digital ischemia treatments to each other,” Dr. Griffith said.

Therapy for vasospasm begins with calcium channel blockers such as amlodipine and nifedipine, she said, followed by phosphodiesterase type 5 inhibitors such as sildenafil or endothelin receptor antagonist medications such as bosentan. “If these fail, we use an IV option – epoprostenol. Other options are sympathectomy surgery, Botox, digital nerve blocks, biofeedback, and SSRIs,” she said. “These treatments work fairly well in most patients, but there are patients who break through these therapies and have ongoing digital ischemia, leading to digital ulcers, pain, infections, acro-osteolysis, and auto-amputation. There is definitely room to improve on our current treatment paradigm.”

For the new study, researchers in Italy led by Amelia Spinella, MD, PhD, of University Hospital of Modena, retrospectively tracked 45 patients with systemic sclerosis and at least one digital ulcer (40 women; average age, 53 years) who were treated in 2019. All patients’ ulcers were resistant to opioid therapy at the maximum tolerated dose, and all had undergone periodic iloprost infusion every 30-40 days. Based on each patient’s clinical situation, they had received calcium-channel blockers, phosphodiesterase type 5 inhibitors (sildenafil), and/or endothelin receptor antagonists (bosentan or macitentan). The researchers noted that all patients underwent surgical debridement regularly following wound bed preparation procedures and received advanced dressings (alginate, hydrocolloid, hydrofiber, hydrogel, and polyurethane foam or film). Of the 45 patients, 25 treated their wounds daily over the course of a month by administering four drops of a preparation of 10% CBD oil in acidic form and 90% hemp oil over the wound bed and perilesional skin and then covering it with a nonadhesive cloth.

“Basal wound-related pain NRS [numeric rating scale] scores decreased from 8.4 (standard deviation [SD], 0.8) at the baseline (T0) to 6.0 (SD, 0.82) after 1 month of CBD treatment (T1; P < .0001),” the researchers reported. “Across the same time period, volitional incident pain NRS scores decreased from 9.32 (SD, 0.75; T0) to 6.8 (SD, 1.12; T1; P < .0001). In addition, mean total hours of sleep per night increased from 2.56 (SD, 1.28) to 5.67 (SD, 0.85) hours (P < .0001).” Twelve of the 25 needed additional painkiller therapy.

Complete digital ulcer healing occurred by the end of the study in 18 of 25 (72%) CBD-treated patients, compared with 6 of 20 (30%) control patients.

In contrast, the control group didn’t see any significant improvement in wound-related pain, volitional incident pain, or sleep. All needed additional painkiller therapy. Six developed ulcer infections and received antibiotics.

No significant adverse effects were reported, although 28% of those in the CBD oil group said they had mild effects such as itch and perilesional erythema.

The authors of the new study called for larger, randomized controlled, multicenter trials to confirm the benefit of CBD topical treatment.

In recent years, researchers have devoted more attention to topical CBD as a treatment for skin conditions. While limited, the evidence suggests they “may be effective for the treatment of various inflammatory skin disorders,” researchers wrote in a 2022 report. “Although promising, additional research is necessary to evaluate efficacy and to determine dosing, safety, and long-term treatment guidelines.”

Dr. Griffith, who did not take part in the new study but is familiar with its findings, said she was especially surprised by the hint that topical CBD improves healing in addition to relieving symptoms. “I thought only pain would be affected. This is a great outcome if it can be replicated.”

As for future research, she said “there are difficulties with reproducing this at a big scale in the U.S. given CBD commercial variability. The big issue is the standardization of CBD extraction and production. It is really hard for us as physicians to know what patients are getting. Some online CBD orders contain THC [the major psychoactive ingredient of cannabis] > 0.3% or no CBD at all.”

Still, she said, “physicians and patients may consider this when standard therapies are not working or causing too many adverse effects,” especially since “the downsides here seem fairly minimal – at worst itchiness and redness that did not prevent patients from continuing in the study.”

No details about study funding were provided. The authors and Dr. Griffith report no disclosures.

Topical cannabidiol (CBD) oil appeared to lower pain scores and reduce painkiller use vs. standard treatment in patients with digital ulcers due to systemic sclerosis, a small new study finds. Patients who received the treatment also showed signs of more healing.

The study, published in Advances in Skin & Wound Care, is far from definitive since it’s retrospective and tracked only 45 patients. But the findings add to other research suggesting dermatologic benefits from the topical use of CBD, an ingredient in cannabis that’s widely available and doesn’t cause people to become high or become addicted.

Anatoliy Sizov/Getty Images

“This is a good first step in trying to address scleroderma digital ulcer pain and healing,” University of Colorado rheumatologist Melissa Griffith, MD, said in an interview. “Digital ulcers cause great impact on quality of life, daily activities of living, and pain, so we are always looking for new, effective tools.”

According to Dr. Griffith, digital ulcers occur in scleroderma due to Raynaud’s phenomenon with reversible vasospasm. “Unlike patients with primary Raynaud’s phenomenon, patients will develop ischemia of digits, leading to digital ulcers due to the vasculopathy or vascular remodeling that occurs in scleroderma,” she said.

Current treatments include removal of causative drugs/toxins and warmth, rest, and pain control, although “no trials exist to compare the scleroderma digital ulcer or digital ischemia treatments to each other,” Dr. Griffith said.

Therapy for vasospasm begins with calcium channel blockers such as amlodipine and nifedipine, she said, followed by phosphodiesterase type 5 inhibitors such as sildenafil or endothelin receptor antagonist medications such as bosentan. “If these fail, we use an IV option – epoprostenol. Other options are sympathectomy surgery, Botox, digital nerve blocks, biofeedback, and SSRIs,” she said. “These treatments work fairly well in most patients, but there are patients who break through these therapies and have ongoing digital ischemia, leading to digital ulcers, pain, infections, acro-osteolysis, and auto-amputation. There is definitely room to improve on our current treatment paradigm.”

For the new study, researchers in Italy led by Amelia Spinella, MD, PhD, of University Hospital of Modena, retrospectively tracked 45 patients with systemic sclerosis and at least one digital ulcer (40 women; average age, 53 years) who were treated in 2019. All patients’ ulcers were resistant to opioid therapy at the maximum tolerated dose, and all had undergone periodic iloprost infusion every 30-40 days. Based on each patient’s clinical situation, they had received calcium-channel blockers, phosphodiesterase type 5 inhibitors (sildenafil), and/or endothelin receptor antagonists (bosentan or macitentan). The researchers noted that all patients underwent surgical debridement regularly following wound bed preparation procedures and received advanced dressings (alginate, hydrocolloid, hydrofiber, hydrogel, and polyurethane foam or film). Of the 45 patients, 25 treated their wounds daily over the course of a month by administering four drops of a preparation of 10% CBD oil in acidic form and 90% hemp oil over the wound bed and perilesional skin and then covering it with a nonadhesive cloth.

“Basal wound-related pain NRS [numeric rating scale] scores decreased from 8.4 (standard deviation [SD], 0.8) at the baseline (T0) to 6.0 (SD, 0.82) after 1 month of CBD treatment (T1; P < .0001),” the researchers reported. “Across the same time period, volitional incident pain NRS scores decreased from 9.32 (SD, 0.75; T0) to 6.8 (SD, 1.12; T1; P < .0001). In addition, mean total hours of sleep per night increased from 2.56 (SD, 1.28) to 5.67 (SD, 0.85) hours (P < .0001).” Twelve of the 25 needed additional painkiller therapy.

Complete digital ulcer healing occurred by the end of the study in 18 of 25 (72%) CBD-treated patients, compared with 6 of 20 (30%) control patients.

In contrast, the control group didn’t see any significant improvement in wound-related pain, volitional incident pain, or sleep. All needed additional painkiller therapy. Six developed ulcer infections and received antibiotics.

No significant adverse effects were reported, although 28% of those in the CBD oil group said they had mild effects such as itch and perilesional erythema.

The authors of the new study called for larger, randomized controlled, multicenter trials to confirm the benefit of CBD topical treatment.

In recent years, researchers have devoted more attention to topical CBD as a treatment for skin conditions. While limited, the evidence suggests they “may be effective for the treatment of various inflammatory skin disorders,” researchers wrote in a 2022 report. “Although promising, additional research is necessary to evaluate efficacy and to determine dosing, safety, and long-term treatment guidelines.”

Dr. Griffith, who did not take part in the new study but is familiar with its findings, said she was especially surprised by the hint that topical CBD improves healing in addition to relieving symptoms. “I thought only pain would be affected. This is a great outcome if it can be replicated.”

As for future research, she said “there are difficulties with reproducing this at a big scale in the U.S. given CBD commercial variability. The big issue is the standardization of CBD extraction and production. It is really hard for us as physicians to know what patients are getting. Some online CBD orders contain THC [the major psychoactive ingredient of cannabis] > 0.3% or no CBD at all.”

Still, she said, “physicians and patients may consider this when standard therapies are not working or causing too many adverse effects,” especially since “the downsides here seem fairly minimal – at worst itchiness and redness that did not prevent patients from continuing in the study.”

No details about study funding were provided. The authors and Dr. Griffith report no disclosures.

Topical cannabidiol (CBD) oil appeared to lower pain scores and reduce painkiller use vs. standard treatment in patients with digital ulcers due to systemic sclerosis, a small new study finds. Patients who received the treatment also showed signs of more healing.

The study, published in Advances in Skin & Wound Care, is far from definitive since it’s retrospective and tracked only 45 patients. But the findings add to other research suggesting dermatologic benefits from the topical use of CBD, an ingredient in cannabis that’s widely available and doesn’t cause people to become high or become addicted.

Anatoliy Sizov/Getty Images

“This is a good first step in trying to address scleroderma digital ulcer pain and healing,” University of Colorado rheumatologist Melissa Griffith, MD, said in an interview. “Digital ulcers cause great impact on quality of life, daily activities of living, and pain, so we are always looking for new, effective tools.”

According to Dr. Griffith, digital ulcers occur in scleroderma due to Raynaud’s phenomenon with reversible vasospasm. “Unlike patients with primary Raynaud’s phenomenon, patients will develop ischemia of digits, leading to digital ulcers due to the vasculopathy or vascular remodeling that occurs in scleroderma,” she said.

Current treatments include removal of causative drugs/toxins and warmth, rest, and pain control, although “no trials exist to compare the scleroderma digital ulcer or digital ischemia treatments to each other,” Dr. Griffith said.

Therapy for vasospasm begins with calcium channel blockers such as amlodipine and nifedipine, she said, followed by phosphodiesterase type 5 inhibitors such as sildenafil or endothelin receptor antagonist medications such as bosentan. “If these fail, we use an IV option – epoprostenol. Other options are sympathectomy surgery, Botox, digital nerve blocks, biofeedback, and SSRIs,” she said. “These treatments work fairly well in most patients, but there are patients who break through these therapies and have ongoing digital ischemia, leading to digital ulcers, pain, infections, acro-osteolysis, and auto-amputation. There is definitely room to improve on our current treatment paradigm.”

For the new study, researchers in Italy led by Amelia Spinella, MD, PhD, of University Hospital of Modena, retrospectively tracked 45 patients with systemic sclerosis and at least one digital ulcer (40 women; average age, 53 years) who were treated in 2019. All patients’ ulcers were resistant to opioid therapy at the maximum tolerated dose, and all had undergone periodic iloprost infusion every 30-40 days. Based on each patient’s clinical situation, they had received calcium-channel blockers, phosphodiesterase type 5 inhibitors (sildenafil), and/or endothelin receptor antagonists (bosentan or macitentan). The researchers noted that all patients underwent surgical debridement regularly following wound bed preparation procedures and received advanced dressings (alginate, hydrocolloid, hydrofiber, hydrogel, and polyurethane foam or film). Of the 45 patients, 25 treated their wounds daily over the course of a month by administering four drops of a preparation of 10% CBD oil in acidic form and 90% hemp oil over the wound bed and perilesional skin and then covering it with a nonadhesive cloth.

“Basal wound-related pain NRS [numeric rating scale] scores decreased from 8.4 (standard deviation [SD], 0.8) at the baseline (T0) to 6.0 (SD, 0.82) after 1 month of CBD treatment (T1; P < .0001),” the researchers reported. “Across the same time period, volitional incident pain NRS scores decreased from 9.32 (SD, 0.75; T0) to 6.8 (SD, 1.12; T1; P < .0001). In addition, mean total hours of sleep per night increased from 2.56 (SD, 1.28) to 5.67 (SD, 0.85) hours (P < .0001).” Twelve of the 25 needed additional painkiller therapy.

Complete digital ulcer healing occurred by the end of the study in 18 of 25 (72%) CBD-treated patients, compared with 6 of 20 (30%) control patients.

In contrast, the control group didn’t see any significant improvement in wound-related pain, volitional incident pain, or sleep. All needed additional painkiller therapy. Six developed ulcer infections and received antibiotics.

No significant adverse effects were reported, although 28% of those in the CBD oil group said they had mild effects such as itch and perilesional erythema.

The authors of the new study called for larger, randomized controlled, multicenter trials to confirm the benefit of CBD topical treatment.

In recent years, researchers have devoted more attention to topical CBD as a treatment for skin conditions. While limited, the evidence suggests they “may be effective for the treatment of various inflammatory skin disorders,” researchers wrote in a 2022 report. “Although promising, additional research is necessary to evaluate efficacy and to determine dosing, safety, and long-term treatment guidelines.”

Dr. Griffith, who did not take part in the new study but is familiar with its findings, said she was especially surprised by the hint that topical CBD improves healing in addition to relieving symptoms. “I thought only pain would be affected. This is a great outcome if it can be replicated.”

As for future research, she said “there are difficulties with reproducing this at a big scale in the U.S. given CBD commercial variability. The big issue is the standardization of CBD extraction and production. It is really hard for us as physicians to know what patients are getting. Some online CBD orders contain THC [the major psychoactive ingredient of cannabis] > 0.3% or no CBD at all.”

Still, she said, “physicians and patients may consider this when standard therapies are not working or causing too many adverse effects,” especially since “the downsides here seem fairly minimal – at worst itchiness and redness that did not prevent patients from continuing in the study.”

No details about study funding were provided. The authors and Dr. Griffith report no disclosures.