AVAHO

A cohort study has found increases in mortality rates among women with non-endometrioid uterine carcinoma, despite incident rates that have stabilized. After correction with hysterectomy, mortality risk was about doubled for Black women, compared with White women, and these results could not be explained by differences in cancer subtype or cancer stage at diagnosis. Non-endometroid uterine carcinoma represents 15%-20% of uterine cancers diagnosed and carries a worse prognosis.

“We do not know why non-endometrioid subtypes are disproportionately increasing among all women, nor do we understand why they are so much more common among non-Hispanic Black women. We need more research to identify risk factors and exposures more specifically associated with non-endometrioid cancers to better understand the strong increases in this subtype among all women and the particularly high rates and recent increases in non-Hispanic black women,” said lead author Megan Clarke, PhD, MHS, the study’s lead author and a cancer epidemiologist with the National Cancer Institute.

The study was published online in JAMA Oncology.

“Physicians should be aware that both incidence and mortality rates of non-endometrioid cancers are on the rise. Because these subtypes are rarer than endometrioid uterine cancers, physicians may be less familiar with diagnosing and treating these aggressive types of cancers. Increasing awareness among clinicians and patients regarding the signs and symptoms of uterine cancer (such as postmenopausal bleeding) and the differences in histologic subtypes among racial and ethnic groups may promote earlier diagnosis and timely referral to appropriate treatment,” Dr. Clarke said.

Previous studies based on death certificates found increased mortality, especially in Black women, but they were limited by an inability to link mortality to tumor characteristics. To address this, the researchers linked mortality data to records of 208,587 women diagnosed with uterine cancer between 2000 and 2017, drawn from the U.S. Surveillance, Epidemiology, and End Results (SEER) Program.

Black women represented 9.7% of cases, but they suffered 17.7% of uterine cancer deaths. Overall, mortality from uterine corpus cancer increased by 1.8% per year (95% confidence interval, 1.5%-2.9%). Non-endometroid cancers increased at 2.7% per year (95% CI, 1.8%-3.6%), and this was higher in Asian (3.4%; 95% CI, 0.3%-6.6%), Black (3.5%; 95% CI, 2.2%-4.9%), Hispanic (6.7%; 95% CI, 1.9%-11.8%), and White women (1.5%; 95% CI, 0.6%-2.4%).

Mortality increased 1.8% per year overall for uterine cancer and 2.7% per year for non-endometrioid uterine cancer. There was no increase in mortality seen in endometrioid cancers.

“The concerning rise in deaths from non-endometrioid cancers warrants clinical attention. Our findings suggest that there may be several factors contributing to racial disparities in uterine cancer mortality. Higher mortality rates among non-Hispanic Black women are partly attributable to higher incidence of tumors with aggressive subtypes and advanced stages. However, non-Hispanic Black women in our study who were diagnosed with less aggressive subtypes and early-stage disease also had the highest mortality rates,” said Dr. Clarke.

That suggests that inequities of treatment and high-quality care may be at least partly to blame, since those factors are known to contribute to differences in uterine cancer outcomes. “Other factors including comorbidities, health care facility characteristics, treatment preferences and adherence, patient and provider communication, provider bias, discrimination and structural racism, and potential biologic differences in response to treatment need to be better understood in terms of how they influence racial disparities,” Dr. Clarke said.

Dr. Clarke reported no relevant disclosures.

A cohort study has found increases in mortality rates among women with non-endometrioid uterine carcinoma, despite incident rates that have stabilized. After correction with hysterectomy, mortality risk was about doubled for Black women, compared with White women, and these results could not be explained by differences in cancer subtype or cancer stage at diagnosis. Non-endometroid uterine carcinoma represents 15%-20% of uterine cancers diagnosed and carries a worse prognosis.

“We do not know why non-endometrioid subtypes are disproportionately increasing among all women, nor do we understand why they are so much more common among non-Hispanic Black women. We need more research to identify risk factors and exposures more specifically associated with non-endometrioid cancers to better understand the strong increases in this subtype among all women and the particularly high rates and recent increases in non-Hispanic black women,” said lead author Megan Clarke, PhD, MHS, the study’s lead author and a cancer epidemiologist with the National Cancer Institute.

The study was published online in JAMA Oncology.

“Physicians should be aware that both incidence and mortality rates of non-endometrioid cancers are on the rise. Because these subtypes are rarer than endometrioid uterine cancers, physicians may be less familiar with diagnosing and treating these aggressive types of cancers. Increasing awareness among clinicians and patients regarding the signs and symptoms of uterine cancer (such as postmenopausal bleeding) and the differences in histologic subtypes among racial and ethnic groups may promote earlier diagnosis and timely referral to appropriate treatment,” Dr. Clarke said.

Previous studies based on death certificates found increased mortality, especially in Black women, but they were limited by an inability to link mortality to tumor characteristics. To address this, the researchers linked mortality data to records of 208,587 women diagnosed with uterine cancer between 2000 and 2017, drawn from the U.S. Surveillance, Epidemiology, and End Results (SEER) Program.

Black women represented 9.7% of cases, but they suffered 17.7% of uterine cancer deaths. Overall, mortality from uterine corpus cancer increased by 1.8% per year (95% confidence interval, 1.5%-2.9%). Non-endometroid cancers increased at 2.7% per year (95% CI, 1.8%-3.6%), and this was higher in Asian (3.4%; 95% CI, 0.3%-6.6%), Black (3.5%; 95% CI, 2.2%-4.9%), Hispanic (6.7%; 95% CI, 1.9%-11.8%), and White women (1.5%; 95% CI, 0.6%-2.4%).

Mortality increased 1.8% per year overall for uterine cancer and 2.7% per year for non-endometrioid uterine cancer. There was no increase in mortality seen in endometrioid cancers.

“The concerning rise in deaths from non-endometrioid cancers warrants clinical attention. Our findings suggest that there may be several factors contributing to racial disparities in uterine cancer mortality. Higher mortality rates among non-Hispanic Black women are partly attributable to higher incidence of tumors with aggressive subtypes and advanced stages. However, non-Hispanic Black women in our study who were diagnosed with less aggressive subtypes and early-stage disease also had the highest mortality rates,” said Dr. Clarke.

That suggests that inequities of treatment and high-quality care may be at least partly to blame, since those factors are known to contribute to differences in uterine cancer outcomes. “Other factors including comorbidities, health care facility characteristics, treatment preferences and adherence, patient and provider communication, provider bias, discrimination and structural racism, and potential biologic differences in response to treatment need to be better understood in terms of how they influence racial disparities,” Dr. Clarke said.

Dr. Clarke reported no relevant disclosures.

A cohort study has found increases in mortality rates among women with non-endometrioid uterine carcinoma, despite incident rates that have stabilized. After correction with hysterectomy, mortality risk was about doubled for Black women, compared with White women, and these results could not be explained by differences in cancer subtype or cancer stage at diagnosis. Non-endometroid uterine carcinoma represents 15%-20% of uterine cancers diagnosed and carries a worse prognosis.

“We do not know why non-endometrioid subtypes are disproportionately increasing among all women, nor do we understand why they are so much more common among non-Hispanic Black women. We need more research to identify risk factors and exposures more specifically associated with non-endometrioid cancers to better understand the strong increases in this subtype among all women and the particularly high rates and recent increases in non-Hispanic black women,” said lead author Megan Clarke, PhD, MHS, the study’s lead author and a cancer epidemiologist with the National Cancer Institute.

The study was published online in JAMA Oncology.

“Physicians should be aware that both incidence and mortality rates of non-endometrioid cancers are on the rise. Because these subtypes are rarer than endometrioid uterine cancers, physicians may be less familiar with diagnosing and treating these aggressive types of cancers. Increasing awareness among clinicians and patients regarding the signs and symptoms of uterine cancer (such as postmenopausal bleeding) and the differences in histologic subtypes among racial and ethnic groups may promote earlier diagnosis and timely referral to appropriate treatment,” Dr. Clarke said.

Previous studies based on death certificates found increased mortality, especially in Black women, but they were limited by an inability to link mortality to tumor characteristics. To address this, the researchers linked mortality data to records of 208,587 women diagnosed with uterine cancer between 2000 and 2017, drawn from the U.S. Surveillance, Epidemiology, and End Results (SEER) Program.

Black women represented 9.7% of cases, but they suffered 17.7% of uterine cancer deaths. Overall, mortality from uterine corpus cancer increased by 1.8% per year (95% confidence interval, 1.5%-2.9%). Non-endometroid cancers increased at 2.7% per year (95% CI, 1.8%-3.6%), and this was higher in Asian (3.4%; 95% CI, 0.3%-6.6%), Black (3.5%; 95% CI, 2.2%-4.9%), Hispanic (6.7%; 95% CI, 1.9%-11.8%), and White women (1.5%; 95% CI, 0.6%-2.4%).

Mortality increased 1.8% per year overall for uterine cancer and 2.7% per year for non-endometrioid uterine cancer. There was no increase in mortality seen in endometrioid cancers.

“The concerning rise in deaths from non-endometrioid cancers warrants clinical attention. Our findings suggest that there may be several factors contributing to racial disparities in uterine cancer mortality. Higher mortality rates among non-Hispanic Black women are partly attributable to higher incidence of tumors with aggressive subtypes and advanced stages. However, non-Hispanic Black women in our study who were diagnosed with less aggressive subtypes and early-stage disease also had the highest mortality rates,” said Dr. Clarke.

That suggests that inequities of treatment and high-quality care may be at least partly to blame, since those factors are known to contribute to differences in uterine cancer outcomes. “Other factors including comorbidities, health care facility characteristics, treatment preferences and adherence, patient and provider communication, provider bias, discrimination and structural racism, and potential biologic differences in response to treatment need to be better understood in terms of how they influence racial disparities,” Dr. Clarke said.

Dr. Clarke reported no relevant disclosures.

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

The first prospective study to evaluate the accuracy of a blood test for people being screened for colorectal cancer (CRC) revealed a high sensitivity and specificity.

At 90% specificity, the blood assay (Guardant Health) was 100% sensitive for detecting CRC. At 95% specificity, sensitivity was 88%.

The blood assay detects circulating tumor DNA from cancer in the bloodstream, which is then analyzed for multiple factors, including cancer genetics and methylation.

Lead author Paloma Peinado, MD, a medical oncologist at HM Hospitales, Madrid, and colleagues, called the results similar to those seen with noninvasive, stool-based testing, noting that the “sensitivity and specificity of the blood-based test reached clinically significant thresholds.”

“The reported performance, combined with a more acceptable mode of testing, suggests that this blood-based test may be a viable CRC screening option,” they added.

The study was presented at Digestive Disease Week^® (DDW) 2022, held virtually and in San Diego.

Dr. Peinado and colleagues studied 557 people who agreed to have blood drawn at the time of their colonoscopy. They enrolled participants at four hospitals in Spain.

One-third of participants (33%) who sought CRC screening were at average risk. Of the remainder, 49% were symptomatic, 11% had a positive family history of CRC, 6% had a positive stool-based test result, and 1% presented for colonoscopy for other reasons.

The prospective observational study included people age 45-84 years. The median age of participants was 55 years, and just over half (52%) were women.

The prevalence rate of colorectal adenocarcinoma was 2.6%. Eight patients had stage I cancer, three had stage II cancer, two had stage III cancer, and two had stage IV cancer.

The study was designed to follow patients for 1 year after screening. To date, 14% of participants have reached this point.

Not a general population screening study

“We definitely we need more studies like this,” said Barbara H. Jung, MD, chair of the department of medicine at the University of Washington, Seattle, when asked to comment on the study.

“We need to find other ways to detect colorectal cancer early, to enhance the screening, and to broaden it to a larger population who may not be amenable to the other techniques.”

Dr. Jung added a caveat that the study population included people at a higher risk for CRC. Therefore, she said, it was a screening study but not a general population, average-risk screening study.

However, she said, “that does not mean that this could not be optimized in the future.”  

Ideally, we need tests for every application, including people who are asymptomatic, Dr. Jung said.

Dr. Peinado reports no relevant financial relationships. Some of the study authors are employees of Guardant Health. Dr. Jung reports no relevant financial relationships.

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

The first prospective study to evaluate the accuracy of a blood test for people being screened for colorectal cancer (CRC) revealed a high sensitivity and specificity.

At 90% specificity, the blood assay (Guardant Health) was 100% sensitive for detecting CRC. At 95% specificity, sensitivity was 88%.

The blood assay detects circulating tumor DNA from cancer in the bloodstream, which is then analyzed for multiple factors, including cancer genetics and methylation.

Lead author Paloma Peinado, MD, a medical oncologist at HM Hospitales, Madrid, and colleagues, called the results similar to those seen with noninvasive, stool-based testing, noting that the “sensitivity and specificity of the blood-based test reached clinically significant thresholds.”

“The reported performance, combined with a more acceptable mode of testing, suggests that this blood-based test may be a viable CRC screening option,” they added.

The study was presented at Digestive Disease Week^® (DDW) 2022, held virtually and in San Diego.

Dr. Peinado and colleagues studied 557 people who agreed to have blood drawn at the time of their colonoscopy. They enrolled participants at four hospitals in Spain.

One-third of participants (33%) who sought CRC screening were at average risk. Of the remainder, 49% were symptomatic, 11% had a positive family history of CRC, 6% had a positive stool-based test result, and 1% presented for colonoscopy for other reasons.

The prospective observational study included people age 45-84 years. The median age of participants was 55 years, and just over half (52%) were women.

The prevalence rate of colorectal adenocarcinoma was 2.6%. Eight patients had stage I cancer, three had stage II cancer, two had stage III cancer, and two had stage IV cancer.

The study was designed to follow patients for 1 year after screening. To date, 14% of participants have reached this point.

Not a general population screening study

“We definitely we need more studies like this,” said Barbara H. Jung, MD, chair of the department of medicine at the University of Washington, Seattle, when asked to comment on the study.

“We need to find other ways to detect colorectal cancer early, to enhance the screening, and to broaden it to a larger population who may not be amenable to the other techniques.”

Dr. Jung added a caveat that the study population included people at a higher risk for CRC. Therefore, she said, it was a screening study but not a general population, average-risk screening study.

However, she said, “that does not mean that this could not be optimized in the future.”  

Ideally, we need tests for every application, including people who are asymptomatic, Dr. Jung said.

Dr. Peinado reports no relevant financial relationships. Some of the study authors are employees of Guardant Health. Dr. Jung reports no relevant financial relationships.

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

The first prospective study to evaluate the accuracy of a blood test for people being screened for colorectal cancer (CRC) revealed a high sensitivity and specificity.

At 90% specificity, the blood assay (Guardant Health) was 100% sensitive for detecting CRC. At 95% specificity, sensitivity was 88%.

The blood assay detects circulating tumor DNA from cancer in the bloodstream, which is then analyzed for multiple factors, including cancer genetics and methylation.

Lead author Paloma Peinado, MD, a medical oncologist at HM Hospitales, Madrid, and colleagues, called the results similar to those seen with noninvasive, stool-based testing, noting that the “sensitivity and specificity of the blood-based test reached clinically significant thresholds.”

“The reported performance, combined with a more acceptable mode of testing, suggests that this blood-based test may be a viable CRC screening option,” they added.

The study was presented at Digestive Disease Week^® (DDW) 2022, held virtually and in San Diego.

Dr. Peinado and colleagues studied 557 people who agreed to have blood drawn at the time of their colonoscopy. They enrolled participants at four hospitals in Spain.

One-third of participants (33%) who sought CRC screening were at average risk. Of the remainder, 49% were symptomatic, 11% had a positive family history of CRC, 6% had a positive stool-based test result, and 1% presented for colonoscopy for other reasons.

The prospective observational study included people age 45-84 years. The median age of participants was 55 years, and just over half (52%) were women.

The prevalence rate of colorectal adenocarcinoma was 2.6%. Eight patients had stage I cancer, three had stage II cancer, two had stage III cancer, and two had stage IV cancer.

The study was designed to follow patients for 1 year after screening. To date, 14% of participants have reached this point.

Not a general population screening study

“We definitely we need more studies like this,” said Barbara H. Jung, MD, chair of the department of medicine at the University of Washington, Seattle, when asked to comment on the study.

“We need to find other ways to detect colorectal cancer early, to enhance the screening, and to broaden it to a larger population who may not be amenable to the other techniques.”

Dr. Jung added a caveat that the study population included people at a higher risk for CRC. Therefore, she said, it was a screening study but not a general population, average-risk screening study.

However, she said, “that does not mean that this could not be optimized in the future.”  

Ideally, we need tests for every application, including people who are asymptomatic, Dr. Jung said.

Dr. Peinado reports no relevant financial relationships. Some of the study authors are employees of Guardant Health. Dr. Jung reports no relevant financial relationships.

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

Some smokers might not get lung cancer because of their DNA, researchers report in a new study.

These people have genes that help limit mutations to DNA that would turn cells malignant and make them grow into tumors, the researchers say.

Scientists have long suspected that smoking leads to lung cancer by triggering DNA mutations in healthy cells. But it was hard for them to identify the mutations in healthy cells that might help predict future cancer risk, Jan Vijg, PhD, a senior author of the study and researcher at the University School of Medicine, Shanghai, China, said in a statement.

His team used a process called single-cell whole genome sequencing to examine cells lining the lungs of 19 smokers and 14 nonsmokers ranging in age from their pre-teens to their mid-80s. The cells came from patients who had tissue samples collected from their lungs during diagnostic testing unrelated to cancer. The scientists reported their findings in Nature Genetics.

The researchers specifically looked at cells lining the lungs because these cells can survive for years and build up mutations over time that are linked to aging and smoking.

“Of all the lung’s cell types, these are among the most likely to become cancerous,” says Simon Spivack, MD, a senior author of the study and professor at the Albert Einstein College of Medicine, New York.

Smokers had far more gene mutations that can cause lung cancer than nonsmokers, the analysis found.

“This experimentally confirms that smoking increases lung cancer risk by increasing the frequency of mutations, as previously hypothesized,” says Dr. Spivack. “This is likely one reason why so few nonsmokers get lung cancer, while 10 to 20 percent of lifelong smokers do.”

Among the smokers, people had smoked a maximum of 116 pack-years. A pack-year is the equivalent of smoking one pack a day for a year. The number of mutations detected in smokers’ lung cells increased in direct proportion to the number of pack-years they smoked.

But after 23 pack-years, the lung cells in smokers didn’t appear to add more mutations, the researchers report, suggesting that some people’s genes might make them more likely to fight mutations.

“The heaviest smokers did not have the highest mutation burden,” says Dr. Spivack. “Our data suggest that these individuals may have survived for so long in spite of their heavy smoking because they managed to suppress further mutation accumulation.”

While it’s possible these findings could one day help doctors come up with better ways to screen for lung cancer and treat the disease, that’s still a long way off. Many more lab tests and larger studies will be needed to better pinpoint which smokers might be more prone to lung cancer and why.

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

Some smokers might not get lung cancer because of their DNA, researchers report in a new study.

These people have genes that help limit mutations to DNA that would turn cells malignant and make them grow into tumors, the researchers say.

Scientists have long suspected that smoking leads to lung cancer by triggering DNA mutations in healthy cells. But it was hard for them to identify the mutations in healthy cells that might help predict future cancer risk, Jan Vijg, PhD, a senior author of the study and researcher at the University School of Medicine, Shanghai, China, said in a statement.

His team used a process called single-cell whole genome sequencing to examine cells lining the lungs of 19 smokers and 14 nonsmokers ranging in age from their pre-teens to their mid-80s. The cells came from patients who had tissue samples collected from their lungs during diagnostic testing unrelated to cancer. The scientists reported their findings in Nature Genetics.

The researchers specifically looked at cells lining the lungs because these cells can survive for years and build up mutations over time that are linked to aging and smoking.

“Of all the lung’s cell types, these are among the most likely to become cancerous,” says Simon Spivack, MD, a senior author of the study and professor at the Albert Einstein College of Medicine, New York.

Smokers had far more gene mutations that can cause lung cancer than nonsmokers, the analysis found.

“This experimentally confirms that smoking increases lung cancer risk by increasing the frequency of mutations, as previously hypothesized,” says Dr. Spivack. “This is likely one reason why so few nonsmokers get lung cancer, while 10 to 20 percent of lifelong smokers do.”

Among the smokers, people had smoked a maximum of 116 pack-years. A pack-year is the equivalent of smoking one pack a day for a year. The number of mutations detected in smokers’ lung cells increased in direct proportion to the number of pack-years they smoked.

But after 23 pack-years, the lung cells in smokers didn’t appear to add more mutations, the researchers report, suggesting that some people’s genes might make them more likely to fight mutations.

“The heaviest smokers did not have the highest mutation burden,” says Dr. Spivack. “Our data suggest that these individuals may have survived for so long in spite of their heavy smoking because they managed to suppress further mutation accumulation.”

While it’s possible these findings could one day help doctors come up with better ways to screen for lung cancer and treat the disease, that’s still a long way off. Many more lab tests and larger studies will be needed to better pinpoint which smokers might be more prone to lung cancer and why.

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

Some smokers might not get lung cancer because of their DNA, researchers report in a new study.

These people have genes that help limit mutations to DNA that would turn cells malignant and make them grow into tumors, the researchers say.

Scientists have long suspected that smoking leads to lung cancer by triggering DNA mutations in healthy cells. But it was hard for them to identify the mutations in healthy cells that might help predict future cancer risk, Jan Vijg, PhD, a senior author of the study and researcher at the University School of Medicine, Shanghai, China, said in a statement.

His team used a process called single-cell whole genome sequencing to examine cells lining the lungs of 19 smokers and 14 nonsmokers ranging in age from their pre-teens to their mid-80s. The cells came from patients who had tissue samples collected from their lungs during diagnostic testing unrelated to cancer. The scientists reported their findings in Nature Genetics.

The researchers specifically looked at cells lining the lungs because these cells can survive for years and build up mutations over time that are linked to aging and smoking.

“Of all the lung’s cell types, these are among the most likely to become cancerous,” says Simon Spivack, MD, a senior author of the study and professor at the Albert Einstein College of Medicine, New York.

Smokers had far more gene mutations that can cause lung cancer than nonsmokers, the analysis found.

“This experimentally confirms that smoking increases lung cancer risk by increasing the frequency of mutations, as previously hypothesized,” says Dr. Spivack. “This is likely one reason why so few nonsmokers get lung cancer, while 10 to 20 percent of lifelong smokers do.”

Among the smokers, people had smoked a maximum of 116 pack-years. A pack-year is the equivalent of smoking one pack a day for a year. The number of mutations detected in smokers’ lung cells increased in direct proportion to the number of pack-years they smoked.

But after 23 pack-years, the lung cells in smokers didn’t appear to add more mutations, the researchers report, suggesting that some people’s genes might make them more likely to fight mutations.

“The heaviest smokers did not have the highest mutation burden,” says Dr. Spivack. “Our data suggest that these individuals may have survived for so long in spite of their heavy smoking because they managed to suppress further mutation accumulation.”

While it’s possible these findings could one day help doctors come up with better ways to screen for lung cancer and treat the disease, that’s still a long way off. Many more lab tests and larger studies will be needed to better pinpoint which smokers might be more prone to lung cancer and why.

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

In states that adopted Medicaid expansion following the implementation of the Affordable Care Act (ACA), patients with cancer have improved 2-year overall survival rates, compared with patients in states that did not adopt the expansion.

The finding comes from an American Cancer Society study of more than 2 million patients with newly diagnosed cancer, published online in the Journal of the National Cancer Institute.

The analysis also showed that the evidence was strongest for malignancies with poor prognosis such as lung, pancreatic, and liver cancer, and also for colorectal cancer.

Importantly, improvements in survival were larger in non-Hispanic Black patients and individuals residing in rural areas, suggesting there was a narrowing of disparities in cancer survival by race and rurality.

“Our findings provide further evidence of the importance of expanding Medicaid eligibility in all states, particularly considering the economic crisis and health care disruptions caused by the COVID-19 pandemic,” said lead author Xuesong Han, PhD, scientific director of health services research at the American Cancer Society, in a statement. “What’s encouraging is the American Rescue Plan Act of 2021 provides new incentives for Medicaid expansion in states that have yet to increase eligibility.”

The ACA provided states with incentives to expand Medicaid eligibility to all low-income adults under 138% federal poverty level, regardless of parental status.

As of last month, just 12 states have not yet opted for Medicaid expansion, even though the American Rescue Plan Act of 2021 provides new incentives for those remaining jurisdictions. But to date, none of the remaining states have taken advantage of these new incentives.

An interactive map showing the status of Medicare expansion by state is available here. The 12 states that have not adopted Medicare expansion (as of April) are Alabama, Florida, Georgia, Kansas, Mississippi, North Carolina, South Carolina, South Dakota, Tennessee, Texas, Wisconsin, and Wyoming.  

The benefit of Medicaid expansion on cancer outcomes has already been observed in other studies. The first study to show a survival benefit was presented at the 2020 American Society of Clinical Oncology annual meeting. That analysis showed that cancer mortality declined by 29% in states that expanded Medicaid and by 25% in those that did not. The authors also noted that the greatest mortality benefit was observed in Hispanic patients.
 

Improved survival with expansion

In the current paper, Dr. Han and colleagues used population-based cancer registries from 42 states and compared data on patients aged 18-62 years who were diagnosed with cancer in a period of 2 years before (2010-2012) and after (2014-2016) ACA Medicaid expansion. They were followed through Sept. 30, 2013, and Dec. 31, 2017, respectively.

The analysis involved a total of 2.5 million patients, of whom 1.52 million lived in states that adopted Medicaid expansion and compared with 1 million patients were in states that did not.

Patients with grouped by sex, race and ethnicity, census tract-level poverty, and rurality. The authors note that non-Hispanic Black patients and those from high poverty areas and nonmetropolitan areas were disproportionately represented in nonexpansion states. 

During the 2-year follow-up period, a total of 453,487 deaths occurred (257,950 in expansion states and 195,537 in nonexpansion states).

Overall, patients in expansion states generally had better survival versus those in nonexpansion states, the authors comment. However, for most cancer types, overall survival improved after the ACA for both groups of states.

The 2-year overall survival increased from 80.6% before the ACA to 82.2% post ACA in expansion states and from 78.7% to 80% in nonexpansion states.

This extrapolated to net increase of 0.44 percentage points in expansion states after adjusting for sociodemographic factors. By cancer site, the net increase was greater for colorectal cancer, lung cancer, non-Hodgkin’s lymphoma, pancreatic cancer, and liver cancer.

For Hispanic patients, 2-year survival also increased but was similar in expansion and nonexpansion states, and little net change was associated with Medicaid expansion.

“Our study shows that the increase was largely driven by improvements in survival for cancer types with poor prognosis, suggesting improved access to timely and effective treatments,” said Dr. Han. “It adds to accumulating evidence of the multiple benefits of Medicaid expansion.”

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

In states that adopted Medicaid expansion following the implementation of the Affordable Care Act (ACA), patients with cancer have improved 2-year overall survival rates, compared with patients in states that did not adopt the expansion.

The finding comes from an American Cancer Society study of more than 2 million patients with newly diagnosed cancer, published online in the Journal of the National Cancer Institute.

The analysis also showed that the evidence was strongest for malignancies with poor prognosis such as lung, pancreatic, and liver cancer, and also for colorectal cancer.

Importantly, improvements in survival were larger in non-Hispanic Black patients and individuals residing in rural areas, suggesting there was a narrowing of disparities in cancer survival by race and rurality.

“Our findings provide further evidence of the importance of expanding Medicaid eligibility in all states, particularly considering the economic crisis and health care disruptions caused by the COVID-19 pandemic,” said lead author Xuesong Han, PhD, scientific director of health services research at the American Cancer Society, in a statement. “What’s encouraging is the American Rescue Plan Act of 2021 provides new incentives for Medicaid expansion in states that have yet to increase eligibility.”

The ACA provided states with incentives to expand Medicaid eligibility to all low-income adults under 138% federal poverty level, regardless of parental status.

As of last month, just 12 states have not yet opted for Medicaid expansion, even though the American Rescue Plan Act of 2021 provides new incentives for those remaining jurisdictions. But to date, none of the remaining states have taken advantage of these new incentives.

An interactive map showing the status of Medicare expansion by state is available here. The 12 states that have not adopted Medicare expansion (as of April) are Alabama, Florida, Georgia, Kansas, Mississippi, North Carolina, South Carolina, South Dakota, Tennessee, Texas, Wisconsin, and Wyoming.  

The benefit of Medicaid expansion on cancer outcomes has already been observed in other studies. The first study to show a survival benefit was presented at the 2020 American Society of Clinical Oncology annual meeting. That analysis showed that cancer mortality declined by 29% in states that expanded Medicaid and by 25% in those that did not. The authors also noted that the greatest mortality benefit was observed in Hispanic patients.
 

Improved survival with expansion

In the current paper, Dr. Han and colleagues used population-based cancer registries from 42 states and compared data on patients aged 18-62 years who were diagnosed with cancer in a period of 2 years before (2010-2012) and after (2014-2016) ACA Medicaid expansion. They were followed through Sept. 30, 2013, and Dec. 31, 2017, respectively.

The analysis involved a total of 2.5 million patients, of whom 1.52 million lived in states that adopted Medicaid expansion and compared with 1 million patients were in states that did not.

Patients with grouped by sex, race and ethnicity, census tract-level poverty, and rurality. The authors note that non-Hispanic Black patients and those from high poverty areas and nonmetropolitan areas were disproportionately represented in nonexpansion states. 

During the 2-year follow-up period, a total of 453,487 deaths occurred (257,950 in expansion states and 195,537 in nonexpansion states).

Overall, patients in expansion states generally had better survival versus those in nonexpansion states, the authors comment. However, for most cancer types, overall survival improved after the ACA for both groups of states.

The 2-year overall survival increased from 80.6% before the ACA to 82.2% post ACA in expansion states and from 78.7% to 80% in nonexpansion states.

This extrapolated to net increase of 0.44 percentage points in expansion states after adjusting for sociodemographic factors. By cancer site, the net increase was greater for colorectal cancer, lung cancer, non-Hodgkin’s lymphoma, pancreatic cancer, and liver cancer.

For Hispanic patients, 2-year survival also increased but was similar in expansion and nonexpansion states, and little net change was associated with Medicaid expansion.

“Our study shows that the increase was largely driven by improvements in survival for cancer types with poor prognosis, suggesting improved access to timely and effective treatments,” said Dr. Han. “It adds to accumulating evidence of the multiple benefits of Medicaid expansion.”

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

In states that adopted Medicaid expansion following the implementation of the Affordable Care Act (ACA), patients with cancer have improved 2-year overall survival rates, compared with patients in states that did not adopt the expansion.

The finding comes from an American Cancer Society study of more than 2 million patients with newly diagnosed cancer, published online in the Journal of the National Cancer Institute.

The analysis also showed that the evidence was strongest for malignancies with poor prognosis such as lung, pancreatic, and liver cancer, and also for colorectal cancer.

Importantly, improvements in survival were larger in non-Hispanic Black patients and individuals residing in rural areas, suggesting there was a narrowing of disparities in cancer survival by race and rurality.

“Our findings provide further evidence of the importance of expanding Medicaid eligibility in all states, particularly considering the economic crisis and health care disruptions caused by the COVID-19 pandemic,” said lead author Xuesong Han, PhD, scientific director of health services research at the American Cancer Society, in a statement. “What’s encouraging is the American Rescue Plan Act of 2021 provides new incentives for Medicaid expansion in states that have yet to increase eligibility.”

The ACA provided states with incentives to expand Medicaid eligibility to all low-income adults under 138% federal poverty level, regardless of parental status.

As of last month, just 12 states have not yet opted for Medicaid expansion, even though the American Rescue Plan Act of 2021 provides new incentives for those remaining jurisdictions. But to date, none of the remaining states have taken advantage of these new incentives.

An interactive map showing the status of Medicare expansion by state is available here. The 12 states that have not adopted Medicare expansion (as of April) are Alabama, Florida, Georgia, Kansas, Mississippi, North Carolina, South Carolina, South Dakota, Tennessee, Texas, Wisconsin, and Wyoming.  

The benefit of Medicaid expansion on cancer outcomes has already been observed in other studies. The first study to show a survival benefit was presented at the 2020 American Society of Clinical Oncology annual meeting. That analysis showed that cancer mortality declined by 29% in states that expanded Medicaid and by 25% in those that did not. The authors also noted that the greatest mortality benefit was observed in Hispanic patients.
 

Improved survival with expansion

In the current paper, Dr. Han and colleagues used population-based cancer registries from 42 states and compared data on patients aged 18-62 years who were diagnosed with cancer in a period of 2 years before (2010-2012) and after (2014-2016) ACA Medicaid expansion. They were followed through Sept. 30, 2013, and Dec. 31, 2017, respectively.

The analysis involved a total of 2.5 million patients, of whom 1.52 million lived in states that adopted Medicaid expansion and compared with 1 million patients were in states that did not.

Patients with grouped by sex, race and ethnicity, census tract-level poverty, and rurality. The authors note that non-Hispanic Black patients and those from high poverty areas and nonmetropolitan areas were disproportionately represented in nonexpansion states. 

During the 2-year follow-up period, a total of 453,487 deaths occurred (257,950 in expansion states and 195,537 in nonexpansion states).

Overall, patients in expansion states generally had better survival versus those in nonexpansion states, the authors comment. However, for most cancer types, overall survival improved after the ACA for both groups of states.

The 2-year overall survival increased from 80.6% before the ACA to 82.2% post ACA in expansion states and from 78.7% to 80% in nonexpansion states.

This extrapolated to net increase of 0.44 percentage points in expansion states after adjusting for sociodemographic factors. By cancer site, the net increase was greater for colorectal cancer, lung cancer, non-Hodgkin’s lymphoma, pancreatic cancer, and liver cancer.

For Hispanic patients, 2-year survival also increased but was similar in expansion and nonexpansion states, and little net change was associated with Medicaid expansion.

“Our study shows that the increase was largely driven by improvements in survival for cancer types with poor prognosis, suggesting improved access to timely and effective treatments,” said Dr. Han. “It adds to accumulating evidence of the multiple benefits of Medicaid expansion.”

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

Laparoscopic surgery can improve long-term overall survival (OS) compared with open surgery for patients with rectal cancer, according to findings from a large meta-analysis.

The estimated 5-year OS rate for patients who underwent laparoscopic surgery was 76.2%, vs. 72.7% for those who had open surgery.

“The survival benefit of laparoscopic surgery is encouraging and supports the routine use of laparoscopic surgery for adult patients with rectal cancer in the era of minimally invasive surgery,” wrote the authors, led by Leping Li, MD, of the department of gastrointestinal surgery, Shandong (China) Provincial Hospital.

The article was published online in JAMA Network Open.

Surgery is an essential component in treating rectal cancer, but the benefits of laparoscopic vs. open surgery are not clear. Over the past 15 years, randomized clinical trials (RCTs) have shown comparable long-term outcomes for laparoscopic and open surgery. However, in most meta-analyses that assessed the evidence more broadly, researchers used an “inappropriate” method for the pooled analysis. Dr. Li and colleagues wanted to perform their own meta-analysis to more definitively understand whether the evidence on long-term outcomes supports or opposes the use of laparoscopic surgery for rectal cancer.

In the current study, the authors conducted an individual participant data meta-analysis using time-to-event data and focused on the long-term survival outcomes after laparoscopic or open surgery for adult patients with rectal cancer.

Ten articles involving 12 RCTs and 3,709 participants were included. In these, 2,097 patients were randomly assigned to undergo laparoscopic surgery, and 1,612 were randomly assigned to undergo open surgery. The studies covered a global population, with participants from Europe, North America, and East Asia.

In a one-stage analysis, the authors found that disease-free survival was slightly better among patients who underwent laparoscopic surgery, but the results were statistically similar (hazard ratio [HR], 0.92; P = .26).

However, when it came to OS, those who had undergone laparoscopic surgery fared significantly better (HR, 0.85; P = .02).

These results held up in the two-stage analysis for both disease-free survival (HR, 0.92; P = .25) and OS (HR, 0.85; P = .02). A sensitivity analyses conducted with large RCTs yielded similar pooled effect sizes for disease-free survival (HR, 0.91; P = .20) and OS (HR, 0.84; P = .03).

The authors highlighted several reasons why laparoscopic surgery may be associated with better survival. First, the faster recovery from the minimally invasive procedure could allow patients to begin adjuvant therapy earlier. In addition, the reduced stress responses and higher levels of immune function among patients undergoing minimally invasive surgery may contribute to a long-term survival advantage.

“These findings address concerns regarding the effectiveness of laparoscopic surgery,” the authors wrote. However, “further studies are necessary to explore the specific mechanisms underlying the positive effect of laparoscopic surgery on OS.”

No outside funding source was noted. The authors have disclosed no relevant financial relationships.

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

Laparoscopic surgery can improve long-term overall survival (OS) compared with open surgery for patients with rectal cancer, according to findings from a large meta-analysis.

The estimated 5-year OS rate for patients who underwent laparoscopic surgery was 76.2%, vs. 72.7% for those who had open surgery.

“The survival benefit of laparoscopic surgery is encouraging and supports the routine use of laparoscopic surgery for adult patients with rectal cancer in the era of minimally invasive surgery,” wrote the authors, led by Leping Li, MD, of the department of gastrointestinal surgery, Shandong (China) Provincial Hospital.

The article was published online in JAMA Network Open.

Surgery is an essential component in treating rectal cancer, but the benefits of laparoscopic vs. open surgery are not clear. Over the past 15 years, randomized clinical trials (RCTs) have shown comparable long-term outcomes for laparoscopic and open surgery. However, in most meta-analyses that assessed the evidence more broadly, researchers used an “inappropriate” method for the pooled analysis. Dr. Li and colleagues wanted to perform their own meta-analysis to more definitively understand whether the evidence on long-term outcomes supports or opposes the use of laparoscopic surgery for rectal cancer.

In the current study, the authors conducted an individual participant data meta-analysis using time-to-event data and focused on the long-term survival outcomes after laparoscopic or open surgery for adult patients with rectal cancer.

Ten articles involving 12 RCTs and 3,709 participants were included. In these, 2,097 patients were randomly assigned to undergo laparoscopic surgery, and 1,612 were randomly assigned to undergo open surgery. The studies covered a global population, with participants from Europe, North America, and East Asia.

In a one-stage analysis, the authors found that disease-free survival was slightly better among patients who underwent laparoscopic surgery, but the results were statistically similar (hazard ratio [HR], 0.92; P = .26).

However, when it came to OS, those who had undergone laparoscopic surgery fared significantly better (HR, 0.85; P = .02).

These results held up in the two-stage analysis for both disease-free survival (HR, 0.92; P = .25) and OS (HR, 0.85; P = .02). A sensitivity analyses conducted with large RCTs yielded similar pooled effect sizes for disease-free survival (HR, 0.91; P = .20) and OS (HR, 0.84; P = .03).

The authors highlighted several reasons why laparoscopic surgery may be associated with better survival. First, the faster recovery from the minimally invasive procedure could allow patients to begin adjuvant therapy earlier. In addition, the reduced stress responses and higher levels of immune function among patients undergoing minimally invasive surgery may contribute to a long-term survival advantage.

“These findings address concerns regarding the effectiveness of laparoscopic surgery,” the authors wrote. However, “further studies are necessary to explore the specific mechanisms underlying the positive effect of laparoscopic surgery on OS.”

No outside funding source was noted. The authors have disclosed no relevant financial relationships.

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

Laparoscopic surgery can improve long-term overall survival (OS) compared with open surgery for patients with rectal cancer, according to findings from a large meta-analysis.

The estimated 5-year OS rate for patients who underwent laparoscopic surgery was 76.2%, vs. 72.7% for those who had open surgery.

“The survival benefit of laparoscopic surgery is encouraging and supports the routine use of laparoscopic surgery for adult patients with rectal cancer in the era of minimally invasive surgery,” wrote the authors, led by Leping Li, MD, of the department of gastrointestinal surgery, Shandong (China) Provincial Hospital.

The article was published online in JAMA Network Open.

Surgery is an essential component in treating rectal cancer, but the benefits of laparoscopic vs. open surgery are not clear. Over the past 15 years, randomized clinical trials (RCTs) have shown comparable long-term outcomes for laparoscopic and open surgery. However, in most meta-analyses that assessed the evidence more broadly, researchers used an “inappropriate” method for the pooled analysis. Dr. Li and colleagues wanted to perform their own meta-analysis to more definitively understand whether the evidence on long-term outcomes supports or opposes the use of laparoscopic surgery for rectal cancer.

In the current study, the authors conducted an individual participant data meta-analysis using time-to-event data and focused on the long-term survival outcomes after laparoscopic or open surgery for adult patients with rectal cancer.

Ten articles involving 12 RCTs and 3,709 participants were included. In these, 2,097 patients were randomly assigned to undergo laparoscopic surgery, and 1,612 were randomly assigned to undergo open surgery. The studies covered a global population, with participants from Europe, North America, and East Asia.

In a one-stage analysis, the authors found that disease-free survival was slightly better among patients who underwent laparoscopic surgery, but the results were statistically similar (hazard ratio [HR], 0.92; P = .26).

However, when it came to OS, those who had undergone laparoscopic surgery fared significantly better (HR, 0.85; P = .02).

These results held up in the two-stage analysis for both disease-free survival (HR, 0.92; P = .25) and OS (HR, 0.85; P = .02). A sensitivity analyses conducted with large RCTs yielded similar pooled effect sizes for disease-free survival (HR, 0.91; P = .20) and OS (HR, 0.84; P = .03).

The authors highlighted several reasons why laparoscopic surgery may be associated with better survival. First, the faster recovery from the minimally invasive procedure could allow patients to begin adjuvant therapy earlier. In addition, the reduced stress responses and higher levels of immune function among patients undergoing minimally invasive surgery may contribute to a long-term survival advantage.

“These findings address concerns regarding the effectiveness of laparoscopic surgery,” the authors wrote. However, “further studies are necessary to explore the specific mechanisms underlying the positive effect of laparoscopic surgery on OS.”

No outside funding source was noted. The authors have disclosed no relevant financial relationships.

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

Infertile men may be twice as likely to develop invasive breast cancer as those without fertility issues, according to new research funded by the charity Breast Cancer Now and published in Breast Cancer Research. The study is one of the largest ever into male breast cancer, enabling the team to show a highly statistically significant association.  

A link with infertility had been suspected, since parity markedly reduces the risk of female breast cancer; there are known genetic links in both sexes, and a high risk of both breast cancer and infertility among men with Klinefelter syndrome, suggesting some sex hormone-related involvement. However, the rarity of breast cancer in men – with an annual incidence of about 370 cases and 80 deaths per year in the United Kingdom – meant that past studies were necessarily small and yielded mixed results.

“Compared with previous studies, our study of male breast cancer is large,” said study coauthor Michael Jones, PhD, of the division of genetics and epidemiology at the Institute of Cancer Research (ICR) in London. “It was carried out nationwide across England and Wales and was set in motion more than 15 years ago. Because of how rare male breast cancer is, it took us over 12 years to identify and interview the nearly 2,000 men with breast cancer who were part of this study.”

The latest research is part of the wider Breast Cancer Now Male Breast Cancer Study, launched by the charity in 2007. For the new study, the ICR team interviewed 1,998 males living in England and Wales who had been diagnosed with breast cancer between 2005 and 2017. All were aged under 80 but most 60 or older at diagnosis; 92% of their tumors were invasive, and almost all were estrogen receptor positive (98.5% of those with known status).

Their responses were compared with those of a control group of 1,597 men without breast cancer, matched by age at diagnosis and geographic region, recruited from male non-blood relatives of cases and from husbands of women participating in the Generations cohort study of breast cancer etiology.
 

Raised risk with history of male infertility

Overall, 112 cases (5.6%) and 80 controls (5.0%) reported that they had had infertility problems for which they or their partner had consulted a doctor or infertility clinic. This represented a raised odds ratio of 1.29 (95% confidence interval, 0.94-1.77), which was statistically not significant. However, when analyzed by outcome of the infertility consultation, there was a significant and more than doubled risk of breast cancer among men who were diagnosed as the source of the couple’s infertility (OR = 2.03 [1.18-3.49]), whereas this was not the case among men whose partner was the source (OR = 0.86 [0.51-1.45]) or for whom no source was identified (OR = 1.26 [0.71-2.24]).

In addition, proportionately fewer cases (1,615, or 80.8%) compared with controls (1,423, or 89.1%) had fathered any children, also giving a statistically significantly raised risk of breast cancer for men with no biological children (OR = 1.50 [1.21-1.86], P < .001), “congruent with infertility as a risk factor,” the authors said. The risk was statistically significant for invasive tumors but not for the much smaller number of in situ tumors.

Analysis by number of children showed a decreasing risk with increasing numbers of children, with a highly significant (P < .001) inverse trend where zero was included as a value, but a borderline significant trend (P = .04) if it was not. The team noted that number of children beyond one is difficult to interpret as an indicator of male fertility, since it may more reflect social and cultural factors than fertility per se.

Baseline demographic factors were adjusted for in the risk analyses, and results were not materially changed by sensitivity analyses adjusting additionally for alcohol consumption, smoking, liver disease, and family history of breast cancer. The association also largely remained after exclusion of patients with other preexisting potential confounders including severe obesity and testicular abnormalities, and was consistent irrespective of HER-2 status (there were too few ER-negative tumors to analyze results by ER status).
 

Potential underlying factors

“The causes of breast cancer in men are largely unknown, partly because it is rare and partly because previous studies have been small,” Dr. Jones said. “The evidence presented in our study suggests that the association of infertility and breast cancer should be confirmed with further research, and future investigations are needed into the potential underlying factors, such as hormone imbalances.”

Commenting on the study, Fiona Osgun, senior health information manager at Cancer Research UK, told this news organization: “Overall, there isn’t strong evidence that infertility is a risk factor for male breast cancer. This study helps to shed light onto a cancer type that is sadly still not very well understood, but much more research is needed to say that infertility is a risk factor for male breast cancer.”

She added that although male breast cancer is a rare condition, it’s still important for men to be aware of what looks and feels normal for them, and to be encouraged to seek medical advice if something is not quite right.

A spokesperson for Breast Cancer UK told this news organization: “[We] believe it’s important to understand what leads to breast cancer in men as well as women and that high quality, long-term studies such as this will help with this understanding.

The findings are consistent with an earlier study that found that U.S. men who have never fathered children are at higher risk of breast cancer. This new long-term U.K. study provides strong evidence, which supports this finding.  

“As the authors note, the biological reasons are unclear, but may be associated with altered hormone levels. The ratio of circulating levels of estrogen and androgens (e.g. testosterone) is crucial in healthy functioning of breast tissue. Disruption to this, for example as a result of damage to testes, may affect both fertility and breast cancer risk.

“It is also possible that external factors, such as exposure to certain endocrine (hormone) disrupting chemicals (EDCs), which affect sex hormones, may also affect both fertility and breast cancer risk.

“More studies into breast cancer in men are needed to help us understand better all the risk factors associated with this disease including both hormonal factors and chemical exposures.”

Simon Vincent, PhD, director of research, support, and influencing at Breast Cancer Now, said: “Research has discovered different treatments directed at some features of breast cancer in women; however, breast cancer is not as well understood for men. This is why Breast Cancer Now funds the Male Breast Cancer Study, which looks at what might cause the disease in men. Discovering a link between infertility and male breast cancer is a step towards us understanding male breast cancer and how we could find more ways to diagnose and treat men – and possibly women – with this devastating disease.”

A version of this article first appeared on Medscape UK.

Infertile men may be twice as likely to develop invasive breast cancer as those without fertility issues, according to new research funded by the charity Breast Cancer Now and published in Breast Cancer Research. The study is one of the largest ever into male breast cancer, enabling the team to show a highly statistically significant association.  

A link with infertility had been suspected, since parity markedly reduces the risk of female breast cancer; there are known genetic links in both sexes, and a high risk of both breast cancer and infertility among men with Klinefelter syndrome, suggesting some sex hormone-related involvement. However, the rarity of breast cancer in men – with an annual incidence of about 370 cases and 80 deaths per year in the United Kingdom – meant that past studies were necessarily small and yielded mixed results.

“Compared with previous studies, our study of male breast cancer is large,” said study coauthor Michael Jones, PhD, of the division of genetics and epidemiology at the Institute of Cancer Research (ICR) in London. “It was carried out nationwide across England and Wales and was set in motion more than 15 years ago. Because of how rare male breast cancer is, it took us over 12 years to identify and interview the nearly 2,000 men with breast cancer who were part of this study.”

The latest research is part of the wider Breast Cancer Now Male Breast Cancer Study, launched by the charity in 2007. For the new study, the ICR team interviewed 1,998 males living in England and Wales who had been diagnosed with breast cancer between 2005 and 2017. All were aged under 80 but most 60 or older at diagnosis; 92% of their tumors were invasive, and almost all were estrogen receptor positive (98.5% of those with known status).

Their responses were compared with those of a control group of 1,597 men without breast cancer, matched by age at diagnosis and geographic region, recruited from male non-blood relatives of cases and from husbands of women participating in the Generations cohort study of breast cancer etiology.
 

Raised risk with history of male infertility

Overall, 112 cases (5.6%) and 80 controls (5.0%) reported that they had had infertility problems for which they or their partner had consulted a doctor or infertility clinic. This represented a raised odds ratio of 1.29 (95% confidence interval, 0.94-1.77), which was statistically not significant. However, when analyzed by outcome of the infertility consultation, there was a significant and more than doubled risk of breast cancer among men who were diagnosed as the source of the couple’s infertility (OR = 2.03 [1.18-3.49]), whereas this was not the case among men whose partner was the source (OR = 0.86 [0.51-1.45]) or for whom no source was identified (OR = 1.26 [0.71-2.24]).

In addition, proportionately fewer cases (1,615, or 80.8%) compared with controls (1,423, or 89.1%) had fathered any children, also giving a statistically significantly raised risk of breast cancer for men with no biological children (OR = 1.50 [1.21-1.86], P < .001), “congruent with infertility as a risk factor,” the authors said. The risk was statistically significant for invasive tumors but not for the much smaller number of in situ tumors.

Analysis by number of children showed a decreasing risk with increasing numbers of children, with a highly significant (P < .001) inverse trend where zero was included as a value, but a borderline significant trend (P = .04) if it was not. The team noted that number of children beyond one is difficult to interpret as an indicator of male fertility, since it may more reflect social and cultural factors than fertility per se.

Baseline demographic factors were adjusted for in the risk analyses, and results were not materially changed by sensitivity analyses adjusting additionally for alcohol consumption, smoking, liver disease, and family history of breast cancer. The association also largely remained after exclusion of patients with other preexisting potential confounders including severe obesity and testicular abnormalities, and was consistent irrespective of HER-2 status (there were too few ER-negative tumors to analyze results by ER status).
 

Potential underlying factors

“The causes of breast cancer in men are largely unknown, partly because it is rare and partly because previous studies have been small,” Dr. Jones said. “The evidence presented in our study suggests that the association of infertility and breast cancer should be confirmed with further research, and future investigations are needed into the potential underlying factors, such as hormone imbalances.”

Commenting on the study, Fiona Osgun, senior health information manager at Cancer Research UK, told this news organization: “Overall, there isn’t strong evidence that infertility is a risk factor for male breast cancer. This study helps to shed light onto a cancer type that is sadly still not very well understood, but much more research is needed to say that infertility is a risk factor for male breast cancer.”

She added that although male breast cancer is a rare condition, it’s still important for men to be aware of what looks and feels normal for them, and to be encouraged to seek medical advice if something is not quite right.

A spokesperson for Breast Cancer UK told this news organization: “[We] believe it’s important to understand what leads to breast cancer in men as well as women and that high quality, long-term studies such as this will help with this understanding.

The findings are consistent with an earlier study that found that U.S. men who have never fathered children are at higher risk of breast cancer. This new long-term U.K. study provides strong evidence, which supports this finding.  

“As the authors note, the biological reasons are unclear, but may be associated with altered hormone levels. The ratio of circulating levels of estrogen and androgens (e.g. testosterone) is crucial in healthy functioning of breast tissue. Disruption to this, for example as a result of damage to testes, may affect both fertility and breast cancer risk.

“It is also possible that external factors, such as exposure to certain endocrine (hormone) disrupting chemicals (EDCs), which affect sex hormones, may also affect both fertility and breast cancer risk.

“More studies into breast cancer in men are needed to help us understand better all the risk factors associated with this disease including both hormonal factors and chemical exposures.”

Simon Vincent, PhD, director of research, support, and influencing at Breast Cancer Now, said: “Research has discovered different treatments directed at some features of breast cancer in women; however, breast cancer is not as well understood for men. This is why Breast Cancer Now funds the Male Breast Cancer Study, which looks at what might cause the disease in men. Discovering a link between infertility and male breast cancer is a step towards us understanding male breast cancer and how we could find more ways to diagnose and treat men – and possibly women – with this devastating disease.”

A version of this article first appeared on Medscape UK.

Infertile men may be twice as likely to develop invasive breast cancer as those without fertility issues, according to new research funded by the charity Breast Cancer Now and published in Breast Cancer Research. The study is one of the largest ever into male breast cancer, enabling the team to show a highly statistically significant association.  

A link with infertility had been suspected, since parity markedly reduces the risk of female breast cancer; there are known genetic links in both sexes, and a high risk of both breast cancer and infertility among men with Klinefelter syndrome, suggesting some sex hormone-related involvement. However, the rarity of breast cancer in men – with an annual incidence of about 370 cases and 80 deaths per year in the United Kingdom – meant that past studies were necessarily small and yielded mixed results.

“Compared with previous studies, our study of male breast cancer is large,” said study coauthor Michael Jones, PhD, of the division of genetics and epidemiology at the Institute of Cancer Research (ICR) in London. “It was carried out nationwide across England and Wales and was set in motion more than 15 years ago. Because of how rare male breast cancer is, it took us over 12 years to identify and interview the nearly 2,000 men with breast cancer who were part of this study.”

The latest research is part of the wider Breast Cancer Now Male Breast Cancer Study, launched by the charity in 2007. For the new study, the ICR team interviewed 1,998 males living in England and Wales who had been diagnosed with breast cancer between 2005 and 2017. All were aged under 80 but most 60 or older at diagnosis; 92% of their tumors were invasive, and almost all were estrogen receptor positive (98.5% of those with known status).

Their responses were compared with those of a control group of 1,597 men without breast cancer, matched by age at diagnosis and geographic region, recruited from male non-blood relatives of cases and from husbands of women participating in the Generations cohort study of breast cancer etiology.
 

Raised risk with history of male infertility

Overall, 112 cases (5.6%) and 80 controls (5.0%) reported that they had had infertility problems for which they or their partner had consulted a doctor or infertility clinic. This represented a raised odds ratio of 1.29 (95% confidence interval, 0.94-1.77), which was statistically not significant. However, when analyzed by outcome of the infertility consultation, there was a significant and more than doubled risk of breast cancer among men who were diagnosed as the source of the couple’s infertility (OR = 2.03 [1.18-3.49]), whereas this was not the case among men whose partner was the source (OR = 0.86 [0.51-1.45]) or for whom no source was identified (OR = 1.26 [0.71-2.24]).

In addition, proportionately fewer cases (1,615, or 80.8%) compared with controls (1,423, or 89.1%) had fathered any children, also giving a statistically significantly raised risk of breast cancer for men with no biological children (OR = 1.50 [1.21-1.86], P < .001), “congruent with infertility as a risk factor,” the authors said. The risk was statistically significant for invasive tumors but not for the much smaller number of in situ tumors.

Analysis by number of children showed a decreasing risk with increasing numbers of children, with a highly significant (P < .001) inverse trend where zero was included as a value, but a borderline significant trend (P = .04) if it was not. The team noted that number of children beyond one is difficult to interpret as an indicator of male fertility, since it may more reflect social and cultural factors than fertility per se.

Baseline demographic factors were adjusted for in the risk analyses, and results were not materially changed by sensitivity analyses adjusting additionally for alcohol consumption, smoking, liver disease, and family history of breast cancer. The association also largely remained after exclusion of patients with other preexisting potential confounders including severe obesity and testicular abnormalities, and was consistent irrespective of HER-2 status (there were too few ER-negative tumors to analyze results by ER status).
 

Potential underlying factors

“The causes of breast cancer in men are largely unknown, partly because it is rare and partly because previous studies have been small,” Dr. Jones said. “The evidence presented in our study suggests that the association of infertility and breast cancer should be confirmed with further research, and future investigations are needed into the potential underlying factors, such as hormone imbalances.”

Commenting on the study, Fiona Osgun, senior health information manager at Cancer Research UK, told this news organization: “Overall, there isn’t strong evidence that infertility is a risk factor for male breast cancer. This study helps to shed light onto a cancer type that is sadly still not very well understood, but much more research is needed to say that infertility is a risk factor for male breast cancer.”

She added that although male breast cancer is a rare condition, it’s still important for men to be aware of what looks and feels normal for them, and to be encouraged to seek medical advice if something is not quite right.

A spokesperson for Breast Cancer UK told this news organization: “[We] believe it’s important to understand what leads to breast cancer in men as well as women and that high quality, long-term studies such as this will help with this understanding.

The findings are consistent with an earlier study that found that U.S. men who have never fathered children are at higher risk of breast cancer. This new long-term U.K. study provides strong evidence, which supports this finding.  

“As the authors note, the biological reasons are unclear, but may be associated with altered hormone levels. The ratio of circulating levels of estrogen and androgens (e.g. testosterone) is crucial in healthy functioning of breast tissue. Disruption to this, for example as a result of damage to testes, may affect both fertility and breast cancer risk.

“It is also possible that external factors, such as exposure to certain endocrine (hormone) disrupting chemicals (EDCs), which affect sex hormones, may also affect both fertility and breast cancer risk.

“More studies into breast cancer in men are needed to help us understand better all the risk factors associated with this disease including both hormonal factors and chemical exposures.”

Simon Vincent, PhD, director of research, support, and influencing at Breast Cancer Now, said: “Research has discovered different treatments directed at some features of breast cancer in women; however, breast cancer is not as well understood for men. This is why Breast Cancer Now funds the Male Breast Cancer Study, which looks at what might cause the disease in men. Discovering a link between infertility and male breast cancer is a step towards us understanding male breast cancer and how we could find more ways to diagnose and treat men – and possibly women – with this devastating disease.”

A version of this article first appeared on Medscape UK.

More than 70% of cancer patients do not know that they are at greater risk of deep vein thrombosis (DVT) than the general population. It is up to their physician to discuss this with them.

This link is explained by the authors of an article in Cancer Treatment and Research Communications that reports results of a survey carried out by the European Cancer Patient Coalition (ECPC). “The aim of this pan-European patient survey was to assess patient awareness and knowledge about cancer-associated thrombosis (CAT), including risk factors, signs and symptoms, and interventions, to better prevent and treat CAT,” write the authors. “The idea was to create a sort of starting point for subsequent communication and information strategies and for comparing the results of any action taken in this area,” they add.

A roundtable discussion that included oncology healthcare professionals, policymakers, and patient advocates was convened to discuss and review the evidence regarding their ongoing concerns of excessive CAT-associated morbidity and mortality, as well as patients’ desire for greater CAT awareness.

“These discussions demonstrated that very little change had occurred over the years and that greater knowledge about CAT was still needed across the spectrum of healthcare practitioners and patients, particularly regarding primary and secondary prevention of thrombosis,” the authors write.

It was from this starting point that the idea for the pan-European survey was born. The ECPC, widely viewed as the “unified voice of cancer patients across Europe,” led the survey. This survey spanned six countries (France, Germany, Greece, Italy, United Kingdom, and Spain) and involved 1,365 patients and caregivers. The ECPC survey result was originally released at World Thrombosis Day in late 2018.

In an interview, Anna Falanga, MD, the main author of the article and professor of hematology at the University of Milan-Bicocca, Italy, reviewed the results and explained how to improve knowledge of CAT among patients with cancer.

“Data support that up to 20% of patients with cancer will experience venous thromboembolism (VTE), which is approximately 4–5 times higher than the general population,” said Dr. Falanga, who is also chief of the department of immunohematology and transfusion medicine and the Thrombosis and Hemostasis Center at the Hospital Papa Giovanni XXIII, in Bergamo, Italy.

“We have known about the link between thrombosis and cancer since the 19th century, but it has taken until midway through the last century for our level of understanding and awareness of the problem to reach its current level. Initially, this was limited to fundamental research, with large advances in our understanding of the mechanisms of the link between the two; it has only been more recently that we have had clinical studies that have piqued the interest of healthcare professionals, who were previously uninterested in the topic,” she said.
 

Poor understanding

One piece of data stands out from the European survey: Nearly three quarters of respondents (72%) said that before taking part in the survey, they were not aware that people with cancer have a higher-than-normal risk of developing thrombosis. “We asked participants to rate their overall understanding of CAT on a scale of 1 (low) to 10 (high), with the average (mean) score obtained being 4.1. Only 21% of patients gave a rating of 7 or above (high understanding). The average rating was very similar in the different countries surveyed,” write the authors. They note that the survey also assessed how much participants had learned about the topic from their physicians.

Approximately 35% of patients were made aware of CAT either immediately before or at the time of their cancer diagnosis. Of particular concern, one quarter (26%) of respondents (the largest proportion) noted that they first became aware of CAT when they suffered a blood clot. The average rating was very similar in the different countries surveyed. “Let us not forget that cancer and cancer treatments themselves cause a number of side effects, some of which can be very serious, so in some ways, a clot might be seen as a minor problem. Yet, in reality, it isn’t. It is a significant cause of death and disease in cancer patients,” said Dr. Falanga.

When discussing prevention, most respondents (87%) said they were aware that taking a walk could reduce their risk. Slightly fewer were aware that stopping smoking could reduce their risk (75%), and even fewer were aware that keeping hydrated (63%) and stretching their legs (55%) could reduce their risk.

Symptoms of CAT appeared to be relatively well known; 73% of survey participants indicated that they were aware that swelling in the foot, ankle, or leg could be a sign of DVT, and 71% indicated that shortness of breath could be a sign of pulmonary embolism (PE). “Other symptoms, however, were less well known, with just over half (57%) of participants being aware that pain, cramping, and tenderness could be a sign of DVT. About one third (33%) knew that irregular heartbeat could be a sign of PE. These results varied between countries,” according to the authors.

The survey highlighted that just over a third of respondents said that they were currently using anticoagulants, although almost all (96%) knew that anticoagulants could be used to effectively treat thrombosis. Only 41% of those using anticoagulants said they had been told about any possible side effects.
 

The Italian situation

The report containing the full results of the European survey goes even further, since, in addition to its overall results, it also gives information about individual countries.

The data from Italy, which are based on 246 persons, show that only 27% of patients and caregivers were aware of the increased risk of thrombosis after a cancer diagnosis. This figure is in line with the overall results of the survey, although the average score of the 10-point scale was lower for the Italy cohort (3.3/10 vs 4.1/10).

The results are more variable in terms of knowledge of risk factors. Most respondents (89%) said that they were aware of the risks related to inactivity. Just over half (52%), however, said that they were aware of the risks related to radiotherapy. Nevertheless, 75% of participants knew about the risks relating to cancer surgery and chemotherapy. “To all intents and purposes, all types of cancer drug can significantly affect the risk of developing a clot. And this is also the case for more modern types of treatment, such as immunotherapy,” said Dr. Falanga.

Most respondents reported that they got information about cancer-associated thrombosis verbally, usually from their hospital doctor (11%). Some respondents (6%) said that they found out about it from their own research, usually online. Almost 1 in 4 patients (24%) in Italy said that they first became aware of CAT when they suffered a blood clot. Answers to questions about knowledge of symptoms show that 58% of Italian patients and caregivers know that swelling of the lower limbs can be a symptom of DVT, and the same percentage knows that shortness of breath might indicate PE.

In terms of preventive action, the picture in Italy is somewhat variable: 74% of participants were aware of the importance of walking, but far fewer knew about the need to stop smoking (57%) and stretch the legs (35%). Of the 41% of Italians who were also taking an anticoagulant drug, 53% said that they knew about the possible side effects of such medication.
 

Which way forward?

“The high rate of CAT suggests that, despite the clinical evidence and clear guideline recommendations for patients with cancer, CAT prevention and recognition remain low among healthcare professionals,” the authors write.

The results of the ECPC survey further confirm those of previous studies, highlighting patients’ lack of knowledge about CAT and the need for more in-depth discussions between physician and patient.

So, what can be done? As highlighted by previous studies, “patients’ experiences are an education in themselves, particularly for the oncology care team,” the authors write. “Once the patient has a thrombosis, the opportunity for thrombosis prevention, which should be the most crucial focus of the care clinics (surgical, oncology, and palliative care), is gone,” they add.

“Oncology professionals, as well as other members of the patient’s care team (eg, internists, surgeons, nurses), need to perform better, at every stage of the patient’s cancer pathway, to ensure patients are aware of CAT and their individual risk to develop a blood clot,” said Dr. Falanga. She explained that in this group, it is the general practitioner who is the first contact. “These professionals are on the front line of the battle; they are among the first healthcare workers given the chance to suspect a clot and should, therefore, be fully aware of the increased risk in oncology patients,” she reiterated.

Experts agree on the fact that a multidisciplinary approach is of utmost importance in this context: the different roles in the team must be clear. “It is also fundamental to establish who does what in terms of educating and informing the patient,” said Dr. Falanga.

The researchers also put forward an example of a successful initiative: the Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTE-PACC) program. The initiative was developed by experts from the University of Vermont and was described in a recent article in JCO Oncology Practice.

Numerous resources are available online to help physicians talk to their patients and explain the risks linked to CAT along the continuum of cancer care. Among them is a resource titled, “Cancer Associated Thrombosis (CAT): Be Clot Conscious,” which can be found on the ECPC’s website.

“We have a collective responsibility using the ECPC patient survey as a baseline to inform patients with cancer on how to identify signs and symptoms of CAT to enable faster diagnosis and treatment,” the authors conclude.

This article was translated from Univadis Italy.

More than 70% of cancer patients do not know that they are at greater risk of deep vein thrombosis (DVT) than the general population. It is up to their physician to discuss this with them.

This link is explained by the authors of an article in Cancer Treatment and Research Communications that reports results of a survey carried out by the European Cancer Patient Coalition (ECPC). “The aim of this pan-European patient survey was to assess patient awareness and knowledge about cancer-associated thrombosis (CAT), including risk factors, signs and symptoms, and interventions, to better prevent and treat CAT,” write the authors. “The idea was to create a sort of starting point for subsequent communication and information strategies and for comparing the results of any action taken in this area,” they add.

A roundtable discussion that included oncology healthcare professionals, policymakers, and patient advocates was convened to discuss and review the evidence regarding their ongoing concerns of excessive CAT-associated morbidity and mortality, as well as patients’ desire for greater CAT awareness.

“These discussions demonstrated that very little change had occurred over the years and that greater knowledge about CAT was still needed across the spectrum of healthcare practitioners and patients, particularly regarding primary and secondary prevention of thrombosis,” the authors write.

It was from this starting point that the idea for the pan-European survey was born. The ECPC, widely viewed as the “unified voice of cancer patients across Europe,” led the survey. This survey spanned six countries (France, Germany, Greece, Italy, United Kingdom, and Spain) and involved 1,365 patients and caregivers. The ECPC survey result was originally released at World Thrombosis Day in late 2018.

In an interview, Anna Falanga, MD, the main author of the article and professor of hematology at the University of Milan-Bicocca, Italy, reviewed the results and explained how to improve knowledge of CAT among patients with cancer.

“Data support that up to 20% of patients with cancer will experience venous thromboembolism (VTE), which is approximately 4–5 times higher than the general population,” said Dr. Falanga, who is also chief of the department of immunohematology and transfusion medicine and the Thrombosis and Hemostasis Center at the Hospital Papa Giovanni XXIII, in Bergamo, Italy.

“We have known about the link between thrombosis and cancer since the 19th century, but it has taken until midway through the last century for our level of understanding and awareness of the problem to reach its current level. Initially, this was limited to fundamental research, with large advances in our understanding of the mechanisms of the link between the two; it has only been more recently that we have had clinical studies that have piqued the interest of healthcare professionals, who were previously uninterested in the topic,” she said.
 

Poor understanding

One piece of data stands out from the European survey: Nearly three quarters of respondents (72%) said that before taking part in the survey, they were not aware that people with cancer have a higher-than-normal risk of developing thrombosis. “We asked participants to rate their overall understanding of CAT on a scale of 1 (low) to 10 (high), with the average (mean) score obtained being 4.1. Only 21% of patients gave a rating of 7 or above (high understanding). The average rating was very similar in the different countries surveyed,” write the authors. They note that the survey also assessed how much participants had learned about the topic from their physicians.

Approximately 35% of patients were made aware of CAT either immediately before or at the time of their cancer diagnosis. Of particular concern, one quarter (26%) of respondents (the largest proportion) noted that they first became aware of CAT when they suffered a blood clot. The average rating was very similar in the different countries surveyed. “Let us not forget that cancer and cancer treatments themselves cause a number of side effects, some of which can be very serious, so in some ways, a clot might be seen as a minor problem. Yet, in reality, it isn’t. It is a significant cause of death and disease in cancer patients,” said Dr. Falanga.

When discussing prevention, most respondents (87%) said they were aware that taking a walk could reduce their risk. Slightly fewer were aware that stopping smoking could reduce their risk (75%), and even fewer were aware that keeping hydrated (63%) and stretching their legs (55%) could reduce their risk.

Symptoms of CAT appeared to be relatively well known; 73% of survey participants indicated that they were aware that swelling in the foot, ankle, or leg could be a sign of DVT, and 71% indicated that shortness of breath could be a sign of pulmonary embolism (PE). “Other symptoms, however, were less well known, with just over half (57%) of participants being aware that pain, cramping, and tenderness could be a sign of DVT. About one third (33%) knew that irregular heartbeat could be a sign of PE. These results varied between countries,” according to the authors.

The survey highlighted that just over a third of respondents said that they were currently using anticoagulants, although almost all (96%) knew that anticoagulants could be used to effectively treat thrombosis. Only 41% of those using anticoagulants said they had been told about any possible side effects.
 

The Italian situation

The report containing the full results of the European survey goes even further, since, in addition to its overall results, it also gives information about individual countries.

The data from Italy, which are based on 246 persons, show that only 27% of patients and caregivers were aware of the increased risk of thrombosis after a cancer diagnosis. This figure is in line with the overall results of the survey, although the average score of the 10-point scale was lower for the Italy cohort (3.3/10 vs 4.1/10).

The results are more variable in terms of knowledge of risk factors. Most respondents (89%) said that they were aware of the risks related to inactivity. Just over half (52%), however, said that they were aware of the risks related to radiotherapy. Nevertheless, 75% of participants knew about the risks relating to cancer surgery and chemotherapy. “To all intents and purposes, all types of cancer drug can significantly affect the risk of developing a clot. And this is also the case for more modern types of treatment, such as immunotherapy,” said Dr. Falanga.

Most respondents reported that they got information about cancer-associated thrombosis verbally, usually from their hospital doctor (11%). Some respondents (6%) said that they found out about it from their own research, usually online. Almost 1 in 4 patients (24%) in Italy said that they first became aware of CAT when they suffered a blood clot. Answers to questions about knowledge of symptoms show that 58% of Italian patients and caregivers know that swelling of the lower limbs can be a symptom of DVT, and the same percentage knows that shortness of breath might indicate PE.

In terms of preventive action, the picture in Italy is somewhat variable: 74% of participants were aware of the importance of walking, but far fewer knew about the need to stop smoking (57%) and stretch the legs (35%). Of the 41% of Italians who were also taking an anticoagulant drug, 53% said that they knew about the possible side effects of such medication.
 

Which way forward?

“The high rate of CAT suggests that, despite the clinical evidence and clear guideline recommendations for patients with cancer, CAT prevention and recognition remain low among healthcare professionals,” the authors write.

The results of the ECPC survey further confirm those of previous studies, highlighting patients’ lack of knowledge about CAT and the need for more in-depth discussions between physician and patient.

So, what can be done? As highlighted by previous studies, “patients’ experiences are an education in themselves, particularly for the oncology care team,” the authors write. “Once the patient has a thrombosis, the opportunity for thrombosis prevention, which should be the most crucial focus of the care clinics (surgical, oncology, and palliative care), is gone,” they add.

“Oncology professionals, as well as other members of the patient’s care team (eg, internists, surgeons, nurses), need to perform better, at every stage of the patient’s cancer pathway, to ensure patients are aware of CAT and their individual risk to develop a blood clot,” said Dr. Falanga. She explained that in this group, it is the general practitioner who is the first contact. “These professionals are on the front line of the battle; they are among the first healthcare workers given the chance to suspect a clot and should, therefore, be fully aware of the increased risk in oncology patients,” she reiterated.

Experts agree on the fact that a multidisciplinary approach is of utmost importance in this context: the different roles in the team must be clear. “It is also fundamental to establish who does what in terms of educating and informing the patient,” said Dr. Falanga.

The researchers also put forward an example of a successful initiative: the Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTE-PACC) program. The initiative was developed by experts from the University of Vermont and was described in a recent article in JCO Oncology Practice.

Numerous resources are available online to help physicians talk to their patients and explain the risks linked to CAT along the continuum of cancer care. Among them is a resource titled, “Cancer Associated Thrombosis (CAT): Be Clot Conscious,” which can be found on the ECPC’s website.

“We have a collective responsibility using the ECPC patient survey as a baseline to inform patients with cancer on how to identify signs and symptoms of CAT to enable faster diagnosis and treatment,” the authors conclude.

This article was translated from Univadis Italy.

More than 70% of cancer patients do not know that they are at greater risk of deep vein thrombosis (DVT) than the general population. It is up to their physician to discuss this with them.

This link is explained by the authors of an article in Cancer Treatment and Research Communications that reports results of a survey carried out by the European Cancer Patient Coalition (ECPC). “The aim of this pan-European patient survey was to assess patient awareness and knowledge about cancer-associated thrombosis (CAT), including risk factors, signs and symptoms, and interventions, to better prevent and treat CAT,” write the authors. “The idea was to create a sort of starting point for subsequent communication and information strategies and for comparing the results of any action taken in this area,” they add.

A roundtable discussion that included oncology healthcare professionals, policymakers, and patient advocates was convened to discuss and review the evidence regarding their ongoing concerns of excessive CAT-associated morbidity and mortality, as well as patients’ desire for greater CAT awareness.

“These discussions demonstrated that very little change had occurred over the years and that greater knowledge about CAT was still needed across the spectrum of healthcare practitioners and patients, particularly regarding primary and secondary prevention of thrombosis,” the authors write.

It was from this starting point that the idea for the pan-European survey was born. The ECPC, widely viewed as the “unified voice of cancer patients across Europe,” led the survey. This survey spanned six countries (France, Germany, Greece, Italy, United Kingdom, and Spain) and involved 1,365 patients and caregivers. The ECPC survey result was originally released at World Thrombosis Day in late 2018.

In an interview, Anna Falanga, MD, the main author of the article and professor of hematology at the University of Milan-Bicocca, Italy, reviewed the results and explained how to improve knowledge of CAT among patients with cancer.

“Data support that up to 20% of patients with cancer will experience venous thromboembolism (VTE), which is approximately 4–5 times higher than the general population,” said Dr. Falanga, who is also chief of the department of immunohematology and transfusion medicine and the Thrombosis and Hemostasis Center at the Hospital Papa Giovanni XXIII, in Bergamo, Italy.

“We have known about the link between thrombosis and cancer since the 19th century, but it has taken until midway through the last century for our level of understanding and awareness of the problem to reach its current level. Initially, this was limited to fundamental research, with large advances in our understanding of the mechanisms of the link between the two; it has only been more recently that we have had clinical studies that have piqued the interest of healthcare professionals, who were previously uninterested in the topic,” she said.
 

Poor understanding

One piece of data stands out from the European survey: Nearly three quarters of respondents (72%) said that before taking part in the survey, they were not aware that people with cancer have a higher-than-normal risk of developing thrombosis. “We asked participants to rate their overall understanding of CAT on a scale of 1 (low) to 10 (high), with the average (mean) score obtained being 4.1. Only 21% of patients gave a rating of 7 or above (high understanding). The average rating was very similar in the different countries surveyed,” write the authors. They note that the survey also assessed how much participants had learned about the topic from their physicians.

Approximately 35% of patients were made aware of CAT either immediately before or at the time of their cancer diagnosis. Of particular concern, one quarter (26%) of respondents (the largest proportion) noted that they first became aware of CAT when they suffered a blood clot. The average rating was very similar in the different countries surveyed. “Let us not forget that cancer and cancer treatments themselves cause a number of side effects, some of which can be very serious, so in some ways, a clot might be seen as a minor problem. Yet, in reality, it isn’t. It is a significant cause of death and disease in cancer patients,” said Dr. Falanga.

When discussing prevention, most respondents (87%) said they were aware that taking a walk could reduce their risk. Slightly fewer were aware that stopping smoking could reduce their risk (75%), and even fewer were aware that keeping hydrated (63%) and stretching their legs (55%) could reduce their risk.

Symptoms of CAT appeared to be relatively well known; 73% of survey participants indicated that they were aware that swelling in the foot, ankle, or leg could be a sign of DVT, and 71% indicated that shortness of breath could be a sign of pulmonary embolism (PE). “Other symptoms, however, were less well known, with just over half (57%) of participants being aware that pain, cramping, and tenderness could be a sign of DVT. About one third (33%) knew that irregular heartbeat could be a sign of PE. These results varied between countries,” according to the authors.

The survey highlighted that just over a third of respondents said that they were currently using anticoagulants, although almost all (96%) knew that anticoagulants could be used to effectively treat thrombosis. Only 41% of those using anticoagulants said they had been told about any possible side effects.
 

The Italian situation

The report containing the full results of the European survey goes even further, since, in addition to its overall results, it also gives information about individual countries.

The data from Italy, which are based on 246 persons, show that only 27% of patients and caregivers were aware of the increased risk of thrombosis after a cancer diagnosis. This figure is in line with the overall results of the survey, although the average score of the 10-point scale was lower for the Italy cohort (3.3/10 vs 4.1/10).

The results are more variable in terms of knowledge of risk factors. Most respondents (89%) said that they were aware of the risks related to inactivity. Just over half (52%), however, said that they were aware of the risks related to radiotherapy. Nevertheless, 75% of participants knew about the risks relating to cancer surgery and chemotherapy. “To all intents and purposes, all types of cancer drug can significantly affect the risk of developing a clot. And this is also the case for more modern types of treatment, such as immunotherapy,” said Dr. Falanga.

Most respondents reported that they got information about cancer-associated thrombosis verbally, usually from their hospital doctor (11%). Some respondents (6%) said that they found out about it from their own research, usually online. Almost 1 in 4 patients (24%) in Italy said that they first became aware of CAT when they suffered a blood clot. Answers to questions about knowledge of symptoms show that 58% of Italian patients and caregivers know that swelling of the lower limbs can be a symptom of DVT, and the same percentage knows that shortness of breath might indicate PE.

In terms of preventive action, the picture in Italy is somewhat variable: 74% of participants were aware of the importance of walking, but far fewer knew about the need to stop smoking (57%) and stretch the legs (35%). Of the 41% of Italians who were also taking an anticoagulant drug, 53% said that they knew about the possible side effects of such medication.
 

Which way forward?

“The high rate of CAT suggests that, despite the clinical evidence and clear guideline recommendations for patients with cancer, CAT prevention and recognition remain low among healthcare professionals,” the authors write.

The results of the ECPC survey further confirm those of previous studies, highlighting patients’ lack of knowledge about CAT and the need for more in-depth discussions between physician and patient.

So, what can be done? As highlighted by previous studies, “patients’ experiences are an education in themselves, particularly for the oncology care team,” the authors write. “Once the patient has a thrombosis, the opportunity for thrombosis prevention, which should be the most crucial focus of the care clinics (surgical, oncology, and palliative care), is gone,” they add.

“Oncology professionals, as well as other members of the patient’s care team (eg, internists, surgeons, nurses), need to perform better, at every stage of the patient’s cancer pathway, to ensure patients are aware of CAT and their individual risk to develop a blood clot,” said Dr. Falanga. She explained that in this group, it is the general practitioner who is the first contact. “These professionals are on the front line of the battle; they are among the first healthcare workers given the chance to suspect a clot and should, therefore, be fully aware of the increased risk in oncology patients,” she reiterated.

Experts agree on the fact that a multidisciplinary approach is of utmost importance in this context: the different roles in the team must be clear. “It is also fundamental to establish who does what in terms of educating and informing the patient,” said Dr. Falanga.

The researchers also put forward an example of a successful initiative: the Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTE-PACC) program. The initiative was developed by experts from the University of Vermont and was described in a recent article in JCO Oncology Practice.

Numerous resources are available online to help physicians talk to their patients and explain the risks linked to CAT along the continuum of cancer care. Among them is a resource titled, “Cancer Associated Thrombosis (CAT): Be Clot Conscious,” which can be found on the ECPC’s website.

“We have a collective responsibility using the ECPC patient survey as a baseline to inform patients with cancer on how to identify signs and symptoms of CAT to enable faster diagnosis and treatment,” the authors conclude.

This article was translated from Univadis Italy.

An injection of bupivacaine following Mohs micrographic surgery procedures that have notable postsurgical pain significantly reduces pain scores and, importantly, use of postsurgical narcotics, a randomized trial shows.

“Single-dose, in-office bupivacaine administration immediately following reconstructions known to be high risk for pain reduces postoperative narcotic use and acute pain during the time period when our patients have the highest levels of pain,” said first author Vanessa B. Voss, MD, of the University of Missouri–Columbia, who presented the findings at the annual meeting of the American College of Mohs Surgery.

Dr. Vanessa Voss

“It was well tolerated, there were no adverse effects, and we recommend the consideration of using this in Mohs micrographic surgery reconstructions that are at the highest risk for pain,” she said.

Recent research has shown that Mohs micrographic surgeons have the highest rates of opioid prescribing of all dermatologists, with about 11% of patients undergoing a Mohs procedure prescribed the drugs for postoperative use, Dr. Voss explained.

Yet, with the ongoing opioid epidemic and even short courses of postoperative opioids placing patients at risk for addiction, the pressure is on to find alternative, nonaddictive strategies for the treatment of acute postoperative pain.

Bupivacaine is commonly used intraoperatively with other types of surgeries to reduce postoperative pain, with a favorable duration of action lasting up to 7 hours, compared with just 2-3 hours with lidocaine. And while its use in Mohs surgery is typically also intraoperative, along with lidocaine, the unique postoperative treatment approach in Mohs surgery has not been well studied, Dr. Voss noted.

To investigate, Dr. Voss and colleagues conducted the prospective, multicenter randomized trial, enrolling 174 patients undergoing Mohs micrographic surgery for skin cancer.

Patients were receiving complex flap reconstructions that have been specifically designated in an American Academy of Dermatology position statement to be high risk for pain following Mohs surgeries, and hence, more likely to involve prescriptions for opioids. These include reconstruction flaps of the scalp, ear, nose or lip, a wedge repair of the ear or lip, or a Mustarde cheek rotation flap.

The mean age of the patients was about 69 years, and about 65% were male. The two groups had no significant differences in demographics, tumor types, or repairs. They were randomized to receive either local injections of bupivacaine 0.5% (with no epinephrine) or placebo with sterile saline injection immediately following the procedure, with the total amount of injection standardized and dependent upon the flap surface area, ranging from 2.5 to 5 cm³.

For postoperative pain, all patients were prescribed acetaminophen 1,000 mg alternating with ibuprofen 400 mg, and tramadol, with instructions to only use tramadol as needed for breakthrough pain.

The reported use of narcotic analgesics by participants was significantly higher among those receiving placebo versus bupivacaine in the first 24 hours following surgery (odds ratio, 2.18; P = .03), as well as in the second 24 hours (OR, 2.18; P = .08) and at 48 hours combined (OR, 2.58; P < .01).

Those in the bupivacaine group also reported lower average pain scores, on a scale of 0-10, during the first 8-hour interval (mean difference, 1.6; P < .001). Importantly, overall, reports of pain medication use and the percentage of patients reporting pain under control were similar between groups, despite lower opioid use in the bupivacaine group.

“The percentage of patients reporting their pain to be under control was similar at all time intervals in both groups, so this means the bupivacaine group had their pain well-controlled despite fewer narcotics, with significant reductions in opioid use,” Dr. Voss noted.

Bupivacaine, though generally regarded as safe, has a reputation for being the most cardiotoxic of the local anesthetic agents; however, there were no such side effects reported in the study. Dr. Voss said the likely explanation is the use of low doses.

“In our study, we had no cardiotoxic effects when using up to 5 cc of 0.5%, which equates to 25 mg per patient,” she explained. This is considered a “very low dose,” since the maximum in the Food and Drug Administration pamphlet for local infiltration is 175 mg per patient every 3 hours, “yet is sufficient for reducing pain/narcotic use.”

She added that “surgeons must be careful to avoid accidental intravascular injection, which could increase risks of systemic toxicity, but this is very rare in the reconstruction settings described.”

Overall, the study suggests a potentially beneficial and unique nonopioid approach that is currently lacking for Mohs procedures associated with a high level of pain. “These findings offer a very effective intervention to reduce postoperative opioid use in this subset of patients,” Dr. Voss told this news organization. “There is not any other intervention that I am aware of to address this, although further study into other long-acting anesthetics may demonstrate similar effects.”

Dr. Justin J. Leitenberger

Commenting on the study, Justin J. Leitenberger, MD, session moderator, said that these “data could be impactful for reducing pain as well as the need for opioid medication after dermatologic surgery, both of which would be significant for our patients and public health outcomes.”

Among the challenges in treating pain following Mohs surgeries is that “every patient has a different pain threshold and expectation after surgery,” said Dr. Leitenberger, assistant professor of medicine and dermatology and codirector of dermatologic surgery, Mohs micrographic surgery, and laser and cosmetic surgery at Oregon Health & Science University, Portland.

“Patients undergoing larger repairs in tense areas of skin can experience increased pain and require prescription pain medication,” he said. “Bupivacaine, in this study, shows promise to provide longer lasting pain control from the surgical appointment and easier bridging to nonopioid pain control.”

Regarding the potential cardiotoxicities associated with the drug, Dr. Leitenberger agreed that the risks are low, and added that many surgeons have, in fact, switched to full use of bupivacaine, as opposed to combination with lidocaine, apparently without problems. “This is a small dose locally to the area after a procedure and I agree that the risks are minuscule,” he said.

“Of note, during national lidocaine shortages over the past few years, many practices transitioned to exclusive use of bupivacaine for the entire Mohs procedure, and [anecdotally], this transition did not result in toxicities that were reported,” Dr. Leitenberger said.

GW Medical Faculty Associates

Commenting further, Vishal Patel, MD, assistant professor of dermatology and hematology/oncology at George Washington University and director of cutaneous oncology at the GW Cancer Center, both in Washington, also agreed that the benefits appear important. “The benefit from using bupivacaine is encouraging on multiple levels,” he said in an interview.

“Given all that we know about opioids and their negative side effect profile as well as their limited help in cutaneous surgery pain control, the use of long-acting anesthetics is an innovative and reasonable approach to provide pain control in the immediate postoperative window when patients tend to have the most pain,” said Dr. Patel, who is also director of dermatologic surgery at George Washington University.

“After this window, acetaminophen and ibuprofen, which have been shown when used in tandem in an alternating schedule to be superior to opioids, provides an effective pain regimen,” he said. “For larger and more pain-sensitive patients, this appears to be a promising combination.”

Dr. Voss, Dr. Leitenberger, and Dr. Patel have reported no relevant financial relationships.

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

An injection of bupivacaine following Mohs micrographic surgery procedures that have notable postsurgical pain significantly reduces pain scores and, importantly, use of postsurgical narcotics, a randomized trial shows.

“Single-dose, in-office bupivacaine administration immediately following reconstructions known to be high risk for pain reduces postoperative narcotic use and acute pain during the time period when our patients have the highest levels of pain,” said first author Vanessa B. Voss, MD, of the University of Missouri–Columbia, who presented the findings at the annual meeting of the American College of Mohs Surgery.

Dr. Vanessa Voss

“It was well tolerated, there were no adverse effects, and we recommend the consideration of using this in Mohs micrographic surgery reconstructions that are at the highest risk for pain,” she said.

Recent research has shown that Mohs micrographic surgeons have the highest rates of opioid prescribing of all dermatologists, with about 11% of patients undergoing a Mohs procedure prescribed the drugs for postoperative use, Dr. Voss explained.

Yet, with the ongoing opioid epidemic and even short courses of postoperative opioids placing patients at risk for addiction, the pressure is on to find alternative, nonaddictive strategies for the treatment of acute postoperative pain.

Bupivacaine is commonly used intraoperatively with other types of surgeries to reduce postoperative pain, with a favorable duration of action lasting up to 7 hours, compared with just 2-3 hours with lidocaine. And while its use in Mohs surgery is typically also intraoperative, along with lidocaine, the unique postoperative treatment approach in Mohs surgery has not been well studied, Dr. Voss noted.

To investigate, Dr. Voss and colleagues conducted the prospective, multicenter randomized trial, enrolling 174 patients undergoing Mohs micrographic surgery for skin cancer.

Patients were receiving complex flap reconstructions that have been specifically designated in an American Academy of Dermatology position statement to be high risk for pain following Mohs surgeries, and hence, more likely to involve prescriptions for opioids. These include reconstruction flaps of the scalp, ear, nose or lip, a wedge repair of the ear or lip, or a Mustarde cheek rotation flap.

The mean age of the patients was about 69 years, and about 65% were male. The two groups had no significant differences in demographics, tumor types, or repairs. They were randomized to receive either local injections of bupivacaine 0.5% (with no epinephrine) or placebo with sterile saline injection immediately following the procedure, with the total amount of injection standardized and dependent upon the flap surface area, ranging from 2.5 to 5 cm³.

For postoperative pain, all patients were prescribed acetaminophen 1,000 mg alternating with ibuprofen 400 mg, and tramadol, with instructions to only use tramadol as needed for breakthrough pain.

The reported use of narcotic analgesics by participants was significantly higher among those receiving placebo versus bupivacaine in the first 24 hours following surgery (odds ratio, 2.18; P = .03), as well as in the second 24 hours (OR, 2.18; P = .08) and at 48 hours combined (OR, 2.58; P < .01).

Those in the bupivacaine group also reported lower average pain scores, on a scale of 0-10, during the first 8-hour interval (mean difference, 1.6; P < .001). Importantly, overall, reports of pain medication use and the percentage of patients reporting pain under control were similar between groups, despite lower opioid use in the bupivacaine group.

“The percentage of patients reporting their pain to be under control was similar at all time intervals in both groups, so this means the bupivacaine group had their pain well-controlled despite fewer narcotics, with significant reductions in opioid use,” Dr. Voss noted.

Bupivacaine, though generally regarded as safe, has a reputation for being the most cardiotoxic of the local anesthetic agents; however, there were no such side effects reported in the study. Dr. Voss said the likely explanation is the use of low doses.

“In our study, we had no cardiotoxic effects when using up to 5 cc of 0.5%, which equates to 25 mg per patient,” she explained. This is considered a “very low dose,” since the maximum in the Food and Drug Administration pamphlet for local infiltration is 175 mg per patient every 3 hours, “yet is sufficient for reducing pain/narcotic use.”

She added that “surgeons must be careful to avoid accidental intravascular injection, which could increase risks of systemic toxicity, but this is very rare in the reconstruction settings described.”

Overall, the study suggests a potentially beneficial and unique nonopioid approach that is currently lacking for Mohs procedures associated with a high level of pain. “These findings offer a very effective intervention to reduce postoperative opioid use in this subset of patients,” Dr. Voss told this news organization. “There is not any other intervention that I am aware of to address this, although further study into other long-acting anesthetics may demonstrate similar effects.”

Dr. Justin J. Leitenberger

Commenting on the study, Justin J. Leitenberger, MD, session moderator, said that these “data could be impactful for reducing pain as well as the need for opioid medication after dermatologic surgery, both of which would be significant for our patients and public health outcomes.”

Among the challenges in treating pain following Mohs surgeries is that “every patient has a different pain threshold and expectation after surgery,” said Dr. Leitenberger, assistant professor of medicine and dermatology and codirector of dermatologic surgery, Mohs micrographic surgery, and laser and cosmetic surgery at Oregon Health & Science University, Portland.

“Patients undergoing larger repairs in tense areas of skin can experience increased pain and require prescription pain medication,” he said. “Bupivacaine, in this study, shows promise to provide longer lasting pain control from the surgical appointment and easier bridging to nonopioid pain control.”

Regarding the potential cardiotoxicities associated with the drug, Dr. Leitenberger agreed that the risks are low, and added that many surgeons have, in fact, switched to full use of bupivacaine, as opposed to combination with lidocaine, apparently without problems. “This is a small dose locally to the area after a procedure and I agree that the risks are minuscule,” he said.

“Of note, during national lidocaine shortages over the past few years, many practices transitioned to exclusive use of bupivacaine for the entire Mohs procedure, and [anecdotally], this transition did not result in toxicities that were reported,” Dr. Leitenberger said.

GW Medical Faculty Associates

Commenting further, Vishal Patel, MD, assistant professor of dermatology and hematology/oncology at George Washington University and director of cutaneous oncology at the GW Cancer Center, both in Washington, also agreed that the benefits appear important. “The benefit from using bupivacaine is encouraging on multiple levels,” he said in an interview.

“Given all that we know about opioids and their negative side effect profile as well as their limited help in cutaneous surgery pain control, the use of long-acting anesthetics is an innovative and reasonable approach to provide pain control in the immediate postoperative window when patients tend to have the most pain,” said Dr. Patel, who is also director of dermatologic surgery at George Washington University.

“After this window, acetaminophen and ibuprofen, which have been shown when used in tandem in an alternating schedule to be superior to opioids, provides an effective pain regimen,” he said. “For larger and more pain-sensitive patients, this appears to be a promising combination.”

Dr. Voss, Dr. Leitenberger, and Dr. Patel have reported no relevant financial relationships.

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

An injection of bupivacaine following Mohs micrographic surgery procedures that have notable postsurgical pain significantly reduces pain scores and, importantly, use of postsurgical narcotics, a randomized trial shows.

“Single-dose, in-office bupivacaine administration immediately following reconstructions known to be high risk for pain reduces postoperative narcotic use and acute pain during the time period when our patients have the highest levels of pain,” said first author Vanessa B. Voss, MD, of the University of Missouri–Columbia, who presented the findings at the annual meeting of the American College of Mohs Surgery.

Dr. Vanessa Voss

“It was well tolerated, there were no adverse effects, and we recommend the consideration of using this in Mohs micrographic surgery reconstructions that are at the highest risk for pain,” she said.

Recent research has shown that Mohs micrographic surgeons have the highest rates of opioid prescribing of all dermatologists, with about 11% of patients undergoing a Mohs procedure prescribed the drugs for postoperative use, Dr. Voss explained.

Yet, with the ongoing opioid epidemic and even short courses of postoperative opioids placing patients at risk for addiction, the pressure is on to find alternative, nonaddictive strategies for the treatment of acute postoperative pain.

Bupivacaine is commonly used intraoperatively with other types of surgeries to reduce postoperative pain, with a favorable duration of action lasting up to 7 hours, compared with just 2-3 hours with lidocaine. And while its use in Mohs surgery is typically also intraoperative, along with lidocaine, the unique postoperative treatment approach in Mohs surgery has not been well studied, Dr. Voss noted.

To investigate, Dr. Voss and colleagues conducted the prospective, multicenter randomized trial, enrolling 174 patients undergoing Mohs micrographic surgery for skin cancer.

Patients were receiving complex flap reconstructions that have been specifically designated in an American Academy of Dermatology position statement to be high risk for pain following Mohs surgeries, and hence, more likely to involve prescriptions for opioids. These include reconstruction flaps of the scalp, ear, nose or lip, a wedge repair of the ear or lip, or a Mustarde cheek rotation flap.

The mean age of the patients was about 69 years, and about 65% were male. The two groups had no significant differences in demographics, tumor types, or repairs. They were randomized to receive either local injections of bupivacaine 0.5% (with no epinephrine) or placebo with sterile saline injection immediately following the procedure, with the total amount of injection standardized and dependent upon the flap surface area, ranging from 2.5 to 5 cm³.

For postoperative pain, all patients were prescribed acetaminophen 1,000 mg alternating with ibuprofen 400 mg, and tramadol, with instructions to only use tramadol as needed for breakthrough pain.

The reported use of narcotic analgesics by participants was significantly higher among those receiving placebo versus bupivacaine in the first 24 hours following surgery (odds ratio, 2.18; P = .03), as well as in the second 24 hours (OR, 2.18; P = .08) and at 48 hours combined (OR, 2.58; P < .01).

Those in the bupivacaine group also reported lower average pain scores, on a scale of 0-10, during the first 8-hour interval (mean difference, 1.6; P < .001). Importantly, overall, reports of pain medication use and the percentage of patients reporting pain under control were similar between groups, despite lower opioid use in the bupivacaine group.

“The percentage of patients reporting their pain to be under control was similar at all time intervals in both groups, so this means the bupivacaine group had their pain well-controlled despite fewer narcotics, with significant reductions in opioid use,” Dr. Voss noted.

Bupivacaine, though generally regarded as safe, has a reputation for being the most cardiotoxic of the local anesthetic agents; however, there were no such side effects reported in the study. Dr. Voss said the likely explanation is the use of low doses.

“In our study, we had no cardiotoxic effects when using up to 5 cc of 0.5%, which equates to 25 mg per patient,” she explained. This is considered a “very low dose,” since the maximum in the Food and Drug Administration pamphlet for local infiltration is 175 mg per patient every 3 hours, “yet is sufficient for reducing pain/narcotic use.”

She added that “surgeons must be careful to avoid accidental intravascular injection, which could increase risks of systemic toxicity, but this is very rare in the reconstruction settings described.”

Overall, the study suggests a potentially beneficial and unique nonopioid approach that is currently lacking for Mohs procedures associated with a high level of pain. “These findings offer a very effective intervention to reduce postoperative opioid use in this subset of patients,” Dr. Voss told this news organization. “There is not any other intervention that I am aware of to address this, although further study into other long-acting anesthetics may demonstrate similar effects.”

Dr. Justin J. Leitenberger

Commenting on the study, Justin J. Leitenberger, MD, session moderator, said that these “data could be impactful for reducing pain as well as the need for opioid medication after dermatologic surgery, both of which would be significant for our patients and public health outcomes.”

Among the challenges in treating pain following Mohs surgeries is that “every patient has a different pain threshold and expectation after surgery,” said Dr. Leitenberger, assistant professor of medicine and dermatology and codirector of dermatologic surgery, Mohs micrographic surgery, and laser and cosmetic surgery at Oregon Health & Science University, Portland.

“Patients undergoing larger repairs in tense areas of skin can experience increased pain and require prescription pain medication,” he said. “Bupivacaine, in this study, shows promise to provide longer lasting pain control from the surgical appointment and easier bridging to nonopioid pain control.”

Regarding the potential cardiotoxicities associated with the drug, Dr. Leitenberger agreed that the risks are low, and added that many surgeons have, in fact, switched to full use of bupivacaine, as opposed to combination with lidocaine, apparently without problems. “This is a small dose locally to the area after a procedure and I agree that the risks are minuscule,” he said.

“Of note, during national lidocaine shortages over the past few years, many practices transitioned to exclusive use of bupivacaine for the entire Mohs procedure, and [anecdotally], this transition did not result in toxicities that were reported,” Dr. Leitenberger said.

GW Medical Faculty Associates

Commenting further, Vishal Patel, MD, assistant professor of dermatology and hematology/oncology at George Washington University and director of cutaneous oncology at the GW Cancer Center, both in Washington, also agreed that the benefits appear important. “The benefit from using bupivacaine is encouraging on multiple levels,” he said in an interview.

“Given all that we know about opioids and their negative side effect profile as well as their limited help in cutaneous surgery pain control, the use of long-acting anesthetics is an innovative and reasonable approach to provide pain control in the immediate postoperative window when patients tend to have the most pain,” said Dr. Patel, who is also director of dermatologic surgery at George Washington University.

“After this window, acetaminophen and ibuprofen, which have been shown when used in tandem in an alternating schedule to be superior to opioids, provides an effective pain regimen,” he said. “For larger and more pain-sensitive patients, this appears to be a promising combination.”

Dr. Voss, Dr. Leitenberger, and Dr. Patel have reported no relevant financial relationships.

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

Among patients with stage II or stage III rectal adenocarcinoma, organ preservation is achievable in up to half of patients who undergo total neoadjuvant chemotherapy (TNT), according to the results from a new randomized phase 2 trial.

The study included 324 patients from 18 centers who were randomized into one of two groups: induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT). Patients in both groups then underwent either total mesorectal excision (TME) or a watch-and-wait strategy, depending on tumor response.

“What the study shows is that the order of the chemo and the radiation dose doesn’t affect survival, but it seems to affect the probability of preserving the rectum. That data is consistent with other studies that have compared head-to-head chemotherapy followed by radiation versus radiation followed by chemotherapy. In addition, the survival rate for this study is no different from other prospective studies that included patients with similar-stage tumors selected by MRI. So the data suggest that you can probably avoid surgery in half of the patients with locally advanced rectal cancer and still achieve similar survival compared to patients treated with more conventional neoadjuvant treatments and mandatory surgery,” said lead author Julio Garcia-Aguilar, MD, PhD, in an interview.

“It is a significant shift in the treatment paradigm, that can potentially benefit half of the 50,000 rectal cancer patients diagnosed every year in the United States,” said Dr. Garcia-Aguilar, chief of colorectal surgery at Memorial Sloan Kettering Cancer Center, New York.

The study was published online in the Journal of Clinical Oncology.

Neoadjuvant CRT, TME, and adjuvant chemotherapy is an effective treatment strategy for locally advanced rectal adenocarcinoma, but the regimen can cause bowel, urinary, and sexual dysfunction. The majority of adverse effects from the therapy can be traced to surgery. In addition, some patients with distal rectal cancer often require a permanent colostomy.

TNT is a newer approach that delivers chemotherapy plus radiotherapy before surgery. It is designed to improve treatment compliance and eradicate micrometastases in advance of surgery.

After a median follow-up of 3 years, disease-free survival (76% in both groups) was similar to historical controls (75%). Both groups had similar rates of local recurrence-free survival (94% each) and distant metastasis–free survival (84% for INCT-CRT and 82% for CRT-CNCT).

Following TNT, 26% of patients were recommended for TME, including 28% in the INCT-CRT group and 24% in the CRT-CNCT group, and the rest offered watchful-waiting. Forty percent of those in the INCT-CRT group and 27% in the CRT-CNCT group who went on to watchful waiting had tumor regrowth. Of these combined 75 patients, 67 underwent successful salvage surgery.

In the intention-to-treat analysis, 53% of patients had a preserved rectum at 3 years (95% confidence interval, 45%-62%) in the CRT-CNCT group versus 41% in the INCT-CRT group (95% CI, 33%-50%; P = .01).

The new results reinforce other results and should contribute to shifting clinical practice, according to Dr. Garcia-Aguilar. “I think what we have learned is that rectal cancers respond to chemotherapy and radiation at a higher rate that we thought previously, but that the response takes time. That’s something that we use currently in an adaptive way to modify the treatment as we observe the tumor response,” he said.

The slow regrowth means that patients can be closely monitored without undue risk, but such an approach demands buy-in from the patient. “The patient needs to be compliant with a close surveillance protocol, because otherwise it can be a disaster. I think that’s really part of the message,” Dr. Garcia-Aguilar said.

Dr. Garcia-Aguilar has an ownership interest in Intuitive Surgical and has advised or consulted for Medtronic, Intuitive Surgical, and Johnson & Johnson.

Among patients with stage II or stage III rectal adenocarcinoma, organ preservation is achievable in up to half of patients who undergo total neoadjuvant chemotherapy (TNT), according to the results from a new randomized phase 2 trial.

The study included 324 patients from 18 centers who were randomized into one of two groups: induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT). Patients in both groups then underwent either total mesorectal excision (TME) or a watch-and-wait strategy, depending on tumor response.

“What the study shows is that the order of the chemo and the radiation dose doesn’t affect survival, but it seems to affect the probability of preserving the rectum. That data is consistent with other studies that have compared head-to-head chemotherapy followed by radiation versus radiation followed by chemotherapy. In addition, the survival rate for this study is no different from other prospective studies that included patients with similar-stage tumors selected by MRI. So the data suggest that you can probably avoid surgery in half of the patients with locally advanced rectal cancer and still achieve similar survival compared to patients treated with more conventional neoadjuvant treatments and mandatory surgery,” said lead author Julio Garcia-Aguilar, MD, PhD, in an interview.

“It is a significant shift in the treatment paradigm, that can potentially benefit half of the 50,000 rectal cancer patients diagnosed every year in the United States,” said Dr. Garcia-Aguilar, chief of colorectal surgery at Memorial Sloan Kettering Cancer Center, New York.

The study was published online in the Journal of Clinical Oncology.

Neoadjuvant CRT, TME, and adjuvant chemotherapy is an effective treatment strategy for locally advanced rectal adenocarcinoma, but the regimen can cause bowel, urinary, and sexual dysfunction. The majority of adverse effects from the therapy can be traced to surgery. In addition, some patients with distal rectal cancer often require a permanent colostomy.

TNT is a newer approach that delivers chemotherapy plus radiotherapy before surgery. It is designed to improve treatment compliance and eradicate micrometastases in advance of surgery.

After a median follow-up of 3 years, disease-free survival (76% in both groups) was similar to historical controls (75%). Both groups had similar rates of local recurrence-free survival (94% each) and distant metastasis–free survival (84% for INCT-CRT and 82% for CRT-CNCT).

Following TNT, 26% of patients were recommended for TME, including 28% in the INCT-CRT group and 24% in the CRT-CNCT group, and the rest offered watchful-waiting. Forty percent of those in the INCT-CRT group and 27% in the CRT-CNCT group who went on to watchful waiting had tumor regrowth. Of these combined 75 patients, 67 underwent successful salvage surgery.

In the intention-to-treat analysis, 53% of patients had a preserved rectum at 3 years (95% confidence interval, 45%-62%) in the CRT-CNCT group versus 41% in the INCT-CRT group (95% CI, 33%-50%; P = .01).

The new results reinforce other results and should contribute to shifting clinical practice, according to Dr. Garcia-Aguilar. “I think what we have learned is that rectal cancers respond to chemotherapy and radiation at a higher rate that we thought previously, but that the response takes time. That’s something that we use currently in an adaptive way to modify the treatment as we observe the tumor response,” he said.

The slow regrowth means that patients can be closely monitored without undue risk, but such an approach demands buy-in from the patient. “The patient needs to be compliant with a close surveillance protocol, because otherwise it can be a disaster. I think that’s really part of the message,” Dr. Garcia-Aguilar said.

Dr. Garcia-Aguilar has an ownership interest in Intuitive Surgical and has advised or consulted for Medtronic, Intuitive Surgical, and Johnson & Johnson.

Among patients with stage II or stage III rectal adenocarcinoma, organ preservation is achievable in up to half of patients who undergo total neoadjuvant chemotherapy (TNT), according to the results from a new randomized phase 2 trial.

The study included 324 patients from 18 centers who were randomized into one of two groups: induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT). Patients in both groups then underwent either total mesorectal excision (TME) or a watch-and-wait strategy, depending on tumor response.

“What the study shows is that the order of the chemo and the radiation dose doesn’t affect survival, but it seems to affect the probability of preserving the rectum. That data is consistent with other studies that have compared head-to-head chemotherapy followed by radiation versus radiation followed by chemotherapy. In addition, the survival rate for this study is no different from other prospective studies that included patients with similar-stage tumors selected by MRI. So the data suggest that you can probably avoid surgery in half of the patients with locally advanced rectal cancer and still achieve similar survival compared to patients treated with more conventional neoadjuvant treatments and mandatory surgery,” said lead author Julio Garcia-Aguilar, MD, PhD, in an interview.

“It is a significant shift in the treatment paradigm, that can potentially benefit half of the 50,000 rectal cancer patients diagnosed every year in the United States,” said Dr. Garcia-Aguilar, chief of colorectal surgery at Memorial Sloan Kettering Cancer Center, New York.

The study was published online in the Journal of Clinical Oncology.

Neoadjuvant CRT, TME, and adjuvant chemotherapy is an effective treatment strategy for locally advanced rectal adenocarcinoma, but the regimen can cause bowel, urinary, and sexual dysfunction. The majority of adverse effects from the therapy can be traced to surgery. In addition, some patients with distal rectal cancer often require a permanent colostomy.

TNT is a newer approach that delivers chemotherapy plus radiotherapy before surgery. It is designed to improve treatment compliance and eradicate micrometastases in advance of surgery.

After a median follow-up of 3 years, disease-free survival (76% in both groups) was similar to historical controls (75%). Both groups had similar rates of local recurrence-free survival (94% each) and distant metastasis–free survival (84% for INCT-CRT and 82% for CRT-CNCT).

Following TNT, 26% of patients were recommended for TME, including 28% in the INCT-CRT group and 24% in the CRT-CNCT group, and the rest offered watchful-waiting. Forty percent of those in the INCT-CRT group and 27% in the CRT-CNCT group who went on to watchful waiting had tumor regrowth. Of these combined 75 patients, 67 underwent successful salvage surgery.

In the intention-to-treat analysis, 53% of patients had a preserved rectum at 3 years (95% confidence interval, 45%-62%) in the CRT-CNCT group versus 41% in the INCT-CRT group (95% CI, 33%-50%; P = .01).

The new results reinforce other results and should contribute to shifting clinical practice, according to Dr. Garcia-Aguilar. “I think what we have learned is that rectal cancers respond to chemotherapy and radiation at a higher rate that we thought previously, but that the response takes time. That’s something that we use currently in an adaptive way to modify the treatment as we observe the tumor response,” he said.

The slow regrowth means that patients can be closely monitored without undue risk, but such an approach demands buy-in from the patient. “The patient needs to be compliant with a close surveillance protocol, because otherwise it can be a disaster. I think that’s really part of the message,” Dr. Garcia-Aguilar said.

Dr. Garcia-Aguilar has an ownership interest in Intuitive Surgical and has advised or consulted for Medtronic, Intuitive Surgical, and Johnson & Johnson.