AVAHO

Giving a boost radiation dose to the tumor bed following breast-conserving surgery and whole breast irradiation (WBI) has been shown to be effective at reducing recurrence of invasive breast cancer, and now a multinational randomized trial has shown that it can do the same for patients with non–low-risk ductal carcinoma in situ (DCIS).

“The results provide the first randomized trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control,” wrote the authors, led by Boon H. Chua, PhD, from the University of New South Wales, Sydney.

Among 1,608 patients with DCIS with at least one clinical or pathological marker for increased risk of local recurrence, 5-year rates of freedom from local recurrence were 97.1% for patients assigned to received a tumor bed boost versus 92.7% for patients who did not receive a boost dose. This difference translated into a hazard ratio for recurrence with radiation boost of 0.47 (P < .001).

“Our results support the use of tumor-bed boost radiation after postoperative WBI in patients with non–low-risk DCIS to optimize local control, and the adoption of moderately hypofractionated whole breast irradiation in practice to improve the balance of local control, toxicity, and socioeconomic burdens of treatment,” the authors wrote in a study published in The Lancet.

The investigators, from cancer centers in Australia, Europe, and Canada, noted that the advent of screening mammography was followed by a substantial increase in the diagnosis of DCIS. They also noted that patients who undergo breast-conserving surgery for DCIS are at risk for local recurrence, and half of recurrences present as invasive disease.

In addition, they said, there were high recurrence rates in randomized clinical for patients with DCIS who received conventionally fractionated WBI without a tumor boost following surgery.

“Further, the inconvenience of a 5- to 6-week course of conventionally fractionated WBI decreased the quality of life of patients. Thus, tailoring radiation dose fractionation according to recurrence risk is a prominent controversy in the radiation treatment of DCIS,” they wrote.
 

Four-way trial

To see whether a tumor-bed boost following WBI and alternative WBI fractionation schedules could improve outcomes for patients with non–low-risk DCIS, the researchers enrolled patients and assigned them on an equal basis to one of four groups, in which they would receive either conventional or hypofractionated WBI with or without a tumor-bed boost.

The conventional WBI regimen consisted of a total of 50 Gy delivered over 25 fractions. The hypofractionated regimen consisted of a total dose of 42.5 Gy delivered in 16 fractions. Patients assigned to get a boost dose to the tumor bed received an additional 16 Gy in eight fractions after WBI.

Of the 1,608 patients enrolled who eligible for randomization, 803 received a boost dose and 805 did not. As noted before, the risk of recurrence at 5 years was significantly lower with boosting, with 5-year free-from-local-recurrence rates of 97.1%, compared with 92.7% for patients who did not get a tumor-bed boost.

There were no significant differences according to fractionation schedule, however: among all randomly assigned patients the rate of 5-year freedom from recurrence was 94.9% for both the conventionally fractionated and hypofractionated WBI groups.

Not surprisingly, patients who received the boost dose had higher rates of grade 2 or greater toxicities, including breast pain (14% vs. 10%; P = .03) and induration (14% vs. 6%; P < .001).

The study was supported by the National Health and Medical Research Council of Australia, Susan G. Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, and Canadian Cancer Trials Group. Dr. Chua disclosed grant support from the organizations and others.

Giving a boost radiation dose to the tumor bed following breast-conserving surgery and whole breast irradiation (WBI) has been shown to be effective at reducing recurrence of invasive breast cancer, and now a multinational randomized trial has shown that it can do the same for patients with non–low-risk ductal carcinoma in situ (DCIS).

“The results provide the first randomized trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control,” wrote the authors, led by Boon H. Chua, PhD, from the University of New South Wales, Sydney.

Among 1,608 patients with DCIS with at least one clinical or pathological marker for increased risk of local recurrence, 5-year rates of freedom from local recurrence were 97.1% for patients assigned to received a tumor bed boost versus 92.7% for patients who did not receive a boost dose. This difference translated into a hazard ratio for recurrence with radiation boost of 0.47 (P < .001).

“Our results support the use of tumor-bed boost radiation after postoperative WBI in patients with non–low-risk DCIS to optimize local control, and the adoption of moderately hypofractionated whole breast irradiation in practice to improve the balance of local control, toxicity, and socioeconomic burdens of treatment,” the authors wrote in a study published in The Lancet.

The investigators, from cancer centers in Australia, Europe, and Canada, noted that the advent of screening mammography was followed by a substantial increase in the diagnosis of DCIS. They also noted that patients who undergo breast-conserving surgery for DCIS are at risk for local recurrence, and half of recurrences present as invasive disease.

In addition, they said, there were high recurrence rates in randomized clinical for patients with DCIS who received conventionally fractionated WBI without a tumor boost following surgery.

“Further, the inconvenience of a 5- to 6-week course of conventionally fractionated WBI decreased the quality of life of patients. Thus, tailoring radiation dose fractionation according to recurrence risk is a prominent controversy in the radiation treatment of DCIS,” they wrote.
 

Four-way trial

To see whether a tumor-bed boost following WBI and alternative WBI fractionation schedules could improve outcomes for patients with non–low-risk DCIS, the researchers enrolled patients and assigned them on an equal basis to one of four groups, in which they would receive either conventional or hypofractionated WBI with or without a tumor-bed boost.

The conventional WBI regimen consisted of a total of 50 Gy delivered over 25 fractions. The hypofractionated regimen consisted of a total dose of 42.5 Gy delivered in 16 fractions. Patients assigned to get a boost dose to the tumor bed received an additional 16 Gy in eight fractions after WBI.

Of the 1,608 patients enrolled who eligible for randomization, 803 received a boost dose and 805 did not. As noted before, the risk of recurrence at 5 years was significantly lower with boosting, with 5-year free-from-local-recurrence rates of 97.1%, compared with 92.7% for patients who did not get a tumor-bed boost.

There were no significant differences according to fractionation schedule, however: among all randomly assigned patients the rate of 5-year freedom from recurrence was 94.9% for both the conventionally fractionated and hypofractionated WBI groups.

Not surprisingly, patients who received the boost dose had higher rates of grade 2 or greater toxicities, including breast pain (14% vs. 10%; P = .03) and induration (14% vs. 6%; P < .001).

The study was supported by the National Health and Medical Research Council of Australia, Susan G. Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, and Canadian Cancer Trials Group. Dr. Chua disclosed grant support from the organizations and others.

Giving a boost radiation dose to the tumor bed following breast-conserving surgery and whole breast irradiation (WBI) has been shown to be effective at reducing recurrence of invasive breast cancer, and now a multinational randomized trial has shown that it can do the same for patients with non–low-risk ductal carcinoma in situ (DCIS).

“The results provide the first randomized trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control,” wrote the authors, led by Boon H. Chua, PhD, from the University of New South Wales, Sydney.

Among 1,608 patients with DCIS with at least one clinical or pathological marker for increased risk of local recurrence, 5-year rates of freedom from local recurrence were 97.1% for patients assigned to received a tumor bed boost versus 92.7% for patients who did not receive a boost dose. This difference translated into a hazard ratio for recurrence with radiation boost of 0.47 (P < .001).

“Our results support the use of tumor-bed boost radiation after postoperative WBI in patients with non–low-risk DCIS to optimize local control, and the adoption of moderately hypofractionated whole breast irradiation in practice to improve the balance of local control, toxicity, and socioeconomic burdens of treatment,” the authors wrote in a study published in The Lancet.

The investigators, from cancer centers in Australia, Europe, and Canada, noted that the advent of screening mammography was followed by a substantial increase in the diagnosis of DCIS. They also noted that patients who undergo breast-conserving surgery for DCIS are at risk for local recurrence, and half of recurrences present as invasive disease.

In addition, they said, there were high recurrence rates in randomized clinical for patients with DCIS who received conventionally fractionated WBI without a tumor boost following surgery.

“Further, the inconvenience of a 5- to 6-week course of conventionally fractionated WBI decreased the quality of life of patients. Thus, tailoring radiation dose fractionation according to recurrence risk is a prominent controversy in the radiation treatment of DCIS,” they wrote.
 

Four-way trial

To see whether a tumor-bed boost following WBI and alternative WBI fractionation schedules could improve outcomes for patients with non–low-risk DCIS, the researchers enrolled patients and assigned them on an equal basis to one of four groups, in which they would receive either conventional or hypofractionated WBI with or without a tumor-bed boost.

The conventional WBI regimen consisted of a total of 50 Gy delivered over 25 fractions. The hypofractionated regimen consisted of a total dose of 42.5 Gy delivered in 16 fractions. Patients assigned to get a boost dose to the tumor bed received an additional 16 Gy in eight fractions after WBI.

Of the 1,608 patients enrolled who eligible for randomization, 803 received a boost dose and 805 did not. As noted before, the risk of recurrence at 5 years was significantly lower with boosting, with 5-year free-from-local-recurrence rates of 97.1%, compared with 92.7% for patients who did not get a tumor-bed boost.

There were no significant differences according to fractionation schedule, however: among all randomly assigned patients the rate of 5-year freedom from recurrence was 94.9% for both the conventionally fractionated and hypofractionated WBI groups.

Not surprisingly, patients who received the boost dose had higher rates of grade 2 or greater toxicities, including breast pain (14% vs. 10%; P = .03) and induration (14% vs. 6%; P < .001).

The study was supported by the National Health and Medical Research Council of Australia, Susan G. Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, and Canadian Cancer Trials Group. Dr. Chua disclosed grant support from the organizations and others.

Endoscopic ultrasound (EUS)–guided through-the-needle biopsies (TTNBs) of pancreatic cystic lesions are sufficient for accurate molecular analysis, which offers a superior alternative to cyst fluid obtained via fine-needle aspiration, based on a prospective study.

For highest diagnostic clarity, next-generation sequencing (NGS) of TTNBs can be paired with histology, lead author Charlotte Vestrup Rift, MD, PhD, of Copenhagen University Hospital, and colleagues reported.

“The diagnostic algorithm for the management of [pancreatic cystic lesions] includes endoscopic ultrasound examination with aspiration of cyst fluid for cytology,” the investigators wrote in Gastrointestinal Endoscopy. “However, the reported sensitivity of cytology is low [at 54%]. A new microforceps, introduced through a 19-gauge needle, has proven useful for procurement of [TTNBs] that represent both the epithelial and stromal component of the cyst wall. TTNBs have a high sensitivity of 86% for the diagnosis of mucinous cysts.”

Dr. Rift and colleagues evaluated the impact of introducing NGS to the diagnostic process. They noted that concomitant mutations in GNAS and KRAS are diagnostic for intraductal papillary mucinous neoplasms (IPMNs), while other mutations have been linked with progression to cancer.

The study involved 101 patients with pancreatic cystic lesions larger than 15 mm in diameter, mean age of 68 years, among whom 91 had residual TTNBs available after microscopic analysis. These samples underwent a 51-gene NGS panel that included the “most prevalent hot-spot mutations.” Diagnoses were sorted into four categories: neoplastic cyst, mucinous cyst, IPMN, or serous cystic neoplasm.

The primary endpoint was diagnostic yield, both for molecular analysis of TTNBs and for molecular analysis plus histopathology of TTNBs. Sensitivity and specificity of NGS were also determined using histopathology as the gold standard.

Relying on NGS alone, diagnostic yields were 44.5% and 27.7% for detecting a mucinous cyst and determining type of cyst, respectively. These yields rose to 73.3% and 70.3%, respectively, when NGS was used with microscopic evaluation. Continuing with this combined approach, sensitivity and specificity were 83.7% and 81.8%, respectively, for the diagnosis of a mucinous cyst. Sensitivity and specificity were higher still, at 87.2% and 84.6%, respectively, for identifying IPMNs.

The adverse-event rate was 9.9%, with a risk of postprocedure acute pancreatitis of 8.9 % and procedure-associated intracystic bleeding of 3%, according to the authors.

Limitations of the study include the relatively small sample size and the single-center design.

“TTNB-NGS is not sufficient as a stand-alone diagnostic tool as of yet but has a high diagnostic yield when combined with microscopic evaluation and subtyping by immunohistochemistry,” the investigators concluded. “The advantage of EUS-TTNB over EUS–[fine-needle aspiration] is the ability to perform detailed cyst subtyping and the high technical success rate of the procedure. ... However, the procedure comes with a risk of adverse events and thus should be offered to patients where the value of an exact diagnosis outweighs the risks.”

“Molecular subtyping is emerging as a useful clinical test for diagnosing pancreatic cysts,” said Margaret Geraldine Keane, MBBS, MSc, of Johns Hopkins Medicine, Baltimore, although she noted that NGS remains expensive and sporadically available, “which limits its clinical utility and incorporation into diagnostic algorithms for pancreatic cysts. In the future, as the cost of sequencing reduces, and availability improves, this may change.”

For now, Dr. Keane advised physicians to reserve molecular subtyping for cases in which “accurate cyst subtyping will change management ... or when other tests have not provided a clear diagnosis.”

She said the present study is valuable because better diagnostic tests are badly needed for patients with pancreatic cysts, considering the high rate of surgical overtreatment.

“Having more diagnostic tests, such as those described in this publication [to be used on their own or in combination] to decide which patients need surgery, is important,” Dr. Keane said who was not involved in the study.

Better diagnostic tests could also improve outcomes for patients with pancreatic cancer, she said, noting a 5-year survival rate of 10%.

“This outcome is in large part attributable to the late stage at which the majority of patients are diagnosed,” Dr. Keane said. “If patients can be diagnosed earlier, survival dramatically improves. Improvements in diagnostic tests for premalignant pancreatic cystic lesions are therefore vital.”

The study was supported by Rigshospitalets Research Foundation, The Novo Nordisk Foundation, The Danish Cancer Society, and others, although they did not have a role in conducting the study or preparing the manuscript. One investigator disclosed a relationship with MediGlobe. The other investigators reported no conflicts of interest. Dr. Keane disclosed no conflicts of interest.

Endoscopic ultrasound (EUS)–guided through-the-needle biopsies (TTNBs) of pancreatic cystic lesions are sufficient for accurate molecular analysis, which offers a superior alternative to cyst fluid obtained via fine-needle aspiration, based on a prospective study.

For highest diagnostic clarity, next-generation sequencing (NGS) of TTNBs can be paired with histology, lead author Charlotte Vestrup Rift, MD, PhD, of Copenhagen University Hospital, and colleagues reported.

“The diagnostic algorithm for the management of [pancreatic cystic lesions] includes endoscopic ultrasound examination with aspiration of cyst fluid for cytology,” the investigators wrote in Gastrointestinal Endoscopy. “However, the reported sensitivity of cytology is low [at 54%]. A new microforceps, introduced through a 19-gauge needle, has proven useful for procurement of [TTNBs] that represent both the epithelial and stromal component of the cyst wall. TTNBs have a high sensitivity of 86% for the diagnosis of mucinous cysts.”

Dr. Rift and colleagues evaluated the impact of introducing NGS to the diagnostic process. They noted that concomitant mutations in GNAS and KRAS are diagnostic for intraductal papillary mucinous neoplasms (IPMNs), while other mutations have been linked with progression to cancer.

The study involved 101 patients with pancreatic cystic lesions larger than 15 mm in diameter, mean age of 68 years, among whom 91 had residual TTNBs available after microscopic analysis. These samples underwent a 51-gene NGS panel that included the “most prevalent hot-spot mutations.” Diagnoses were sorted into four categories: neoplastic cyst, mucinous cyst, IPMN, or serous cystic neoplasm.

The primary endpoint was diagnostic yield, both for molecular analysis of TTNBs and for molecular analysis plus histopathology of TTNBs. Sensitivity and specificity of NGS were also determined using histopathology as the gold standard.

Relying on NGS alone, diagnostic yields were 44.5% and 27.7% for detecting a mucinous cyst and determining type of cyst, respectively. These yields rose to 73.3% and 70.3%, respectively, when NGS was used with microscopic evaluation. Continuing with this combined approach, sensitivity and specificity were 83.7% and 81.8%, respectively, for the diagnosis of a mucinous cyst. Sensitivity and specificity were higher still, at 87.2% and 84.6%, respectively, for identifying IPMNs.

The adverse-event rate was 9.9%, with a risk of postprocedure acute pancreatitis of 8.9 % and procedure-associated intracystic bleeding of 3%, according to the authors.

Limitations of the study include the relatively small sample size and the single-center design.

“TTNB-NGS is not sufficient as a stand-alone diagnostic tool as of yet but has a high diagnostic yield when combined with microscopic evaluation and subtyping by immunohistochemistry,” the investigators concluded. “The advantage of EUS-TTNB over EUS–[fine-needle aspiration] is the ability to perform detailed cyst subtyping and the high technical success rate of the procedure. ... However, the procedure comes with a risk of adverse events and thus should be offered to patients where the value of an exact diagnosis outweighs the risks.”

“Molecular subtyping is emerging as a useful clinical test for diagnosing pancreatic cysts,” said Margaret Geraldine Keane, MBBS, MSc, of Johns Hopkins Medicine, Baltimore, although she noted that NGS remains expensive and sporadically available, “which limits its clinical utility and incorporation into diagnostic algorithms for pancreatic cysts. In the future, as the cost of sequencing reduces, and availability improves, this may change.”

For now, Dr. Keane advised physicians to reserve molecular subtyping for cases in which “accurate cyst subtyping will change management ... or when other tests have not provided a clear diagnosis.”

She said the present study is valuable because better diagnostic tests are badly needed for patients with pancreatic cysts, considering the high rate of surgical overtreatment.

“Having more diagnostic tests, such as those described in this publication [to be used on their own or in combination] to decide which patients need surgery, is important,” Dr. Keane said who was not involved in the study.

Better diagnostic tests could also improve outcomes for patients with pancreatic cancer, she said, noting a 5-year survival rate of 10%.

“This outcome is in large part attributable to the late stage at which the majority of patients are diagnosed,” Dr. Keane said. “If patients can be diagnosed earlier, survival dramatically improves. Improvements in diagnostic tests for premalignant pancreatic cystic lesions are therefore vital.”

The study was supported by Rigshospitalets Research Foundation, The Novo Nordisk Foundation, The Danish Cancer Society, and others, although they did not have a role in conducting the study or preparing the manuscript. One investigator disclosed a relationship with MediGlobe. The other investigators reported no conflicts of interest. Dr. Keane disclosed no conflicts of interest.

Endoscopic ultrasound (EUS)–guided through-the-needle biopsies (TTNBs) of pancreatic cystic lesions are sufficient for accurate molecular analysis, which offers a superior alternative to cyst fluid obtained via fine-needle aspiration, based on a prospective study.

For highest diagnostic clarity, next-generation sequencing (NGS) of TTNBs can be paired with histology, lead author Charlotte Vestrup Rift, MD, PhD, of Copenhagen University Hospital, and colleagues reported.

“The diagnostic algorithm for the management of [pancreatic cystic lesions] includes endoscopic ultrasound examination with aspiration of cyst fluid for cytology,” the investigators wrote in Gastrointestinal Endoscopy. “However, the reported sensitivity of cytology is low [at 54%]. A new microforceps, introduced through a 19-gauge needle, has proven useful for procurement of [TTNBs] that represent both the epithelial and stromal component of the cyst wall. TTNBs have a high sensitivity of 86% for the diagnosis of mucinous cysts.”

Dr. Rift and colleagues evaluated the impact of introducing NGS to the diagnostic process. They noted that concomitant mutations in GNAS and KRAS are diagnostic for intraductal papillary mucinous neoplasms (IPMNs), while other mutations have been linked with progression to cancer.

The study involved 101 patients with pancreatic cystic lesions larger than 15 mm in diameter, mean age of 68 years, among whom 91 had residual TTNBs available after microscopic analysis. These samples underwent a 51-gene NGS panel that included the “most prevalent hot-spot mutations.” Diagnoses were sorted into four categories: neoplastic cyst, mucinous cyst, IPMN, or serous cystic neoplasm.

The primary endpoint was diagnostic yield, both for molecular analysis of TTNBs and for molecular analysis plus histopathology of TTNBs. Sensitivity and specificity of NGS were also determined using histopathology as the gold standard.

Relying on NGS alone, diagnostic yields were 44.5% and 27.7% for detecting a mucinous cyst and determining type of cyst, respectively. These yields rose to 73.3% and 70.3%, respectively, when NGS was used with microscopic evaluation. Continuing with this combined approach, sensitivity and specificity were 83.7% and 81.8%, respectively, for the diagnosis of a mucinous cyst. Sensitivity and specificity were higher still, at 87.2% and 84.6%, respectively, for identifying IPMNs.

The adverse-event rate was 9.9%, with a risk of postprocedure acute pancreatitis of 8.9 % and procedure-associated intracystic bleeding of 3%, according to the authors.

Limitations of the study include the relatively small sample size and the single-center design.

“TTNB-NGS is not sufficient as a stand-alone diagnostic tool as of yet but has a high diagnostic yield when combined with microscopic evaluation and subtyping by immunohistochemistry,” the investigators concluded. “The advantage of EUS-TTNB over EUS–[fine-needle aspiration] is the ability to perform detailed cyst subtyping and the high technical success rate of the procedure. ... However, the procedure comes with a risk of adverse events and thus should be offered to patients where the value of an exact diagnosis outweighs the risks.”

“Molecular subtyping is emerging as a useful clinical test for diagnosing pancreatic cysts,” said Margaret Geraldine Keane, MBBS, MSc, of Johns Hopkins Medicine, Baltimore, although she noted that NGS remains expensive and sporadically available, “which limits its clinical utility and incorporation into diagnostic algorithms for pancreatic cysts. In the future, as the cost of sequencing reduces, and availability improves, this may change.”

For now, Dr. Keane advised physicians to reserve molecular subtyping for cases in which “accurate cyst subtyping will change management ... or when other tests have not provided a clear diagnosis.”

She said the present study is valuable because better diagnostic tests are badly needed for patients with pancreatic cysts, considering the high rate of surgical overtreatment.

“Having more diagnostic tests, such as those described in this publication [to be used on their own or in combination] to decide which patients need surgery, is important,” Dr. Keane said who was not involved in the study.

Better diagnostic tests could also improve outcomes for patients with pancreatic cancer, she said, noting a 5-year survival rate of 10%.

“This outcome is in large part attributable to the late stage at which the majority of patients are diagnosed,” Dr. Keane said. “If patients can be diagnosed earlier, survival dramatically improves. Improvements in diagnostic tests for premalignant pancreatic cystic lesions are therefore vital.”

The study was supported by Rigshospitalets Research Foundation, The Novo Nordisk Foundation, The Danish Cancer Society, and others, although they did not have a role in conducting the study or preparing the manuscript. One investigator disclosed a relationship with MediGlobe. The other investigators reported no conflicts of interest. Dr. Keane disclosed no conflicts of interest.

An international team of researchers have developed a “molecular map” of chronic lymphocytic leukemia (CLL) and used it to refine genetic subtypes and variations that appear to be linked to clinical outcomes.

Released in a report in Nature Genetics, the map has doubled the number of genetic traits linked the disease from around 100 to 202, lead author Binyamin A. Knisbacher, PhD, a postdoctoral fellow at the Broad Institute of MIT and Harvard Medical Schoo, Boston, said in an interview.

“It also delineated the molecular landscape of the two immunoglobulin gene (IGHV) subtypes, refined CLL subtyping, and built richer genetic prognostic models,” he said.

According to Dr. Knisbacher, CLL “has been at the forefront of genomic discovery,” and research has shown that there’s a wide variety of somatic mutations that drive CLL initiation across the patient population. However, as many as 10% of cases don’t appear to be driven by any known genetic variation, he said, and there’s a need to identify more subtypes and “build richer prognostic models of patient survival” based on genetics and multiomics such as genomics, transcriptomics, and epigenomics.

For the new study, researchers analyzed RNA and DNA from 1,095 patients with CLL and 54 patients with monoclonal B cell lymphocytosis and built what they say is the largest CLL dataset in existence. It’s twice the size of previous datasets, Dr. Knisbacher said.

“We found that RNA expression data was extremely informative for characterizing CLL,” Dr. Knisbacher said. “The RNA expression subtypes refined the ‘classic’ two IGHV subtypes. It is well documented that patients with U-CLL (IGHV-unmutated CLL) have substantially worse clinical outcome in comparison to M-CLL patients (IGHV-mutated CLLs). We found that M-CLLs that have RNA expression profiles similar to U-CLLs have worse survival than M-CLLs with a typical expression profile. Failure-free survival was 50% shorter – 5.3 versus 10.7 years median failure-free survival.”

In addition, he said, “U-CLLs with expression similar to M-CLLs had better survival than U-CLLs with an RNA expression profile typical to U-CLLs.”

The researchers have made their molecular map publicly available at https://cllmap.org/. Researchers can use it “to discover more about each subtype of CLL, and these future studies can help to improve clinical prognosis for the benefit of the patient,” Dr. Knisbacher said.

The study authors added that “this molecular foundation may allow for better prediction of response to therapy or provide the basis for rational combination of novel agents.”

Lee Greenberger, PhD, chief science officer of the Leukemia & Lymphoma Society, said in an interview that the study “provides foundational data further subtyping CLL patients and outcomes. It identifies new targets for therapy or diagnostic predictions in the future. This type of foundational work has proven invaluable in the development of new medicines for cancer in general.”

While there are many medications that have improved therapeutic outcomes in CLL, he added, “cures – or life-long disease control –remain elusive for many patients. Therefore, new molecular insights are needed that could personalize therapies or even lead to entirely new therapies.”

In addition, he said, although prevention of CLL still remains elusive, “it is conceivable that some of the mutations found in this paper occur early in the CLL trajectory, perhaps even before the disease is presented clinically.”

The study was funded by the National Institutes of Health and the Broad/IBM Cancer Resistance Research Project. Dr. Knisbacher and several other authors disclose that they are inventors on a patent related to CLL. Several authors report various relationships with industry. Dr. Greenberger has no disclosures.
 

An international team of researchers have developed a “molecular map” of chronic lymphocytic leukemia (CLL) and used it to refine genetic subtypes and variations that appear to be linked to clinical outcomes.

Released in a report in Nature Genetics, the map has doubled the number of genetic traits linked the disease from around 100 to 202, lead author Binyamin A. Knisbacher, PhD, a postdoctoral fellow at the Broad Institute of MIT and Harvard Medical Schoo, Boston, said in an interview.

“It also delineated the molecular landscape of the two immunoglobulin gene (IGHV) subtypes, refined CLL subtyping, and built richer genetic prognostic models,” he said.

According to Dr. Knisbacher, CLL “has been at the forefront of genomic discovery,” and research has shown that there’s a wide variety of somatic mutations that drive CLL initiation across the patient population. However, as many as 10% of cases don’t appear to be driven by any known genetic variation, he said, and there’s a need to identify more subtypes and “build richer prognostic models of patient survival” based on genetics and multiomics such as genomics, transcriptomics, and epigenomics.

For the new study, researchers analyzed RNA and DNA from 1,095 patients with CLL and 54 patients with monoclonal B cell lymphocytosis and built what they say is the largest CLL dataset in existence. It’s twice the size of previous datasets, Dr. Knisbacher said.

“We found that RNA expression data was extremely informative for characterizing CLL,” Dr. Knisbacher said. “The RNA expression subtypes refined the ‘classic’ two IGHV subtypes. It is well documented that patients with U-CLL (IGHV-unmutated CLL) have substantially worse clinical outcome in comparison to M-CLL patients (IGHV-mutated CLLs). We found that M-CLLs that have RNA expression profiles similar to U-CLLs have worse survival than M-CLLs with a typical expression profile. Failure-free survival was 50% shorter – 5.3 versus 10.7 years median failure-free survival.”

In addition, he said, “U-CLLs with expression similar to M-CLLs had better survival than U-CLLs with an RNA expression profile typical to U-CLLs.”

The researchers have made their molecular map publicly available at https://cllmap.org/. Researchers can use it “to discover more about each subtype of CLL, and these future studies can help to improve clinical prognosis for the benefit of the patient,” Dr. Knisbacher said.

The study authors added that “this molecular foundation may allow for better prediction of response to therapy or provide the basis for rational combination of novel agents.”

Lee Greenberger, PhD, chief science officer of the Leukemia & Lymphoma Society, said in an interview that the study “provides foundational data further subtyping CLL patients and outcomes. It identifies new targets for therapy or diagnostic predictions in the future. This type of foundational work has proven invaluable in the development of new medicines for cancer in general.”

While there are many medications that have improved therapeutic outcomes in CLL, he added, “cures – or life-long disease control –remain elusive for many patients. Therefore, new molecular insights are needed that could personalize therapies or even lead to entirely new therapies.”

In addition, he said, although prevention of CLL still remains elusive, “it is conceivable that some of the mutations found in this paper occur early in the CLL trajectory, perhaps even before the disease is presented clinically.”

The study was funded by the National Institutes of Health and the Broad/IBM Cancer Resistance Research Project. Dr. Knisbacher and several other authors disclose that they are inventors on a patent related to CLL. Several authors report various relationships with industry. Dr. Greenberger has no disclosures.
 

An international team of researchers have developed a “molecular map” of chronic lymphocytic leukemia (CLL) and used it to refine genetic subtypes and variations that appear to be linked to clinical outcomes.

Released in a report in Nature Genetics, the map has doubled the number of genetic traits linked the disease from around 100 to 202, lead author Binyamin A. Knisbacher, PhD, a postdoctoral fellow at the Broad Institute of MIT and Harvard Medical Schoo, Boston, said in an interview.

“It also delineated the molecular landscape of the two immunoglobulin gene (IGHV) subtypes, refined CLL subtyping, and built richer genetic prognostic models,” he said.

According to Dr. Knisbacher, CLL “has been at the forefront of genomic discovery,” and research has shown that there’s a wide variety of somatic mutations that drive CLL initiation across the patient population. However, as many as 10% of cases don’t appear to be driven by any known genetic variation, he said, and there’s a need to identify more subtypes and “build richer prognostic models of patient survival” based on genetics and multiomics such as genomics, transcriptomics, and epigenomics.

For the new study, researchers analyzed RNA and DNA from 1,095 patients with CLL and 54 patients with monoclonal B cell lymphocytosis and built what they say is the largest CLL dataset in existence. It’s twice the size of previous datasets, Dr. Knisbacher said.

“We found that RNA expression data was extremely informative for characterizing CLL,” Dr. Knisbacher said. “The RNA expression subtypes refined the ‘classic’ two IGHV subtypes. It is well documented that patients with U-CLL (IGHV-unmutated CLL) have substantially worse clinical outcome in comparison to M-CLL patients (IGHV-mutated CLLs). We found that M-CLLs that have RNA expression profiles similar to U-CLLs have worse survival than M-CLLs with a typical expression profile. Failure-free survival was 50% shorter – 5.3 versus 10.7 years median failure-free survival.”

In addition, he said, “U-CLLs with expression similar to M-CLLs had better survival than U-CLLs with an RNA expression profile typical to U-CLLs.”

The researchers have made their molecular map publicly available at https://cllmap.org/. Researchers can use it “to discover more about each subtype of CLL, and these future studies can help to improve clinical prognosis for the benefit of the patient,” Dr. Knisbacher said.

The study authors added that “this molecular foundation may allow for better prediction of response to therapy or provide the basis for rational combination of novel agents.”

Lee Greenberger, PhD, chief science officer of the Leukemia & Lymphoma Society, said in an interview that the study “provides foundational data further subtyping CLL patients and outcomes. It identifies new targets for therapy or diagnostic predictions in the future. This type of foundational work has proven invaluable in the development of new medicines for cancer in general.”

While there are many medications that have improved therapeutic outcomes in CLL, he added, “cures – or life-long disease control –remain elusive for many patients. Therefore, new molecular insights are needed that could personalize therapies or even lead to entirely new therapies.”

In addition, he said, although prevention of CLL still remains elusive, “it is conceivable that some of the mutations found in this paper occur early in the CLL trajectory, perhaps even before the disease is presented clinically.”

The study was funded by the National Institutes of Health and the Broad/IBM Cancer Resistance Research Project. Dr. Knisbacher and several other authors disclose that they are inventors on a patent related to CLL. Several authors report various relationships with industry. Dr. Greenberger has no disclosures.
 

In June, Rebecca A. Shatsky, MD, a medical oncologist, turned to Twitter for advice: “What do you do/say when a patient won’t believe you that they have #CANCER. As an oncologist this comes up every now and then and proves very difficult, looking to hear how others have dealt and what works best to help patients here.”

About a dozen people weighed in, offering various thoughts on how to approach these thorny situations. One oncologist suggested revisiting the conversation a few days later, after the patient has more time to process; others suggested sharing the pathology report or images with their patient.

Another person simply noted that “if a [patient] doesn’t want to believe they have cancer, no amount of evidence will change that.”

Based on the initial responses, “it appears there is a paucity of answers sadly,” wrote Dr. Shatsky, a breast cancer specialist at University of California, San Diego.

But for Dr. Shatsky, these incidents spoke to another alarming trend: a rampant mistrust of the medical community that is “becoming MORE common instead of less.”
 

‘Erosion of trust’

Overall, experts say that situations like the one Dr. Shatsky described – patients who don’t believe their cancer diagnosis – occur infrequently.

But denial comes in many forms, and complete disbelief is probably the most extreme. Patients may also downplay the severity of their disease, shy away from hearing bad news, or refuse standard treatment or their doctor’s advice.

Like Dr. Shatsky, these experts say they are also seeing a troubling increase in patients who don’t believe their physicians or don’t trust their recommendations.

“I think there’s an erosion of trust in expertise, in general,” said Ronald M. Epstein, MD, professor of family medicine and psychiatry & oncology at the University of Rochester (N.Y.). “People distrust science more than they did maybe 20 or 30 years ago, or at least that seems to be the case.”

Denial and distrust in cancer care are not new. These responses – along with wishful thinking, distraction, and minimization – are long-established responses among oncology patients. In 1972, Avery D. Weisman, MD, a psychiatrist at Harvard Medical School, Boston, wrote his book “On Dying and Denying,” and ever since, denial and similar responses have been explored in the oncology literature.

Much of this research has focused on the latter stages of illness, but denial can be present at diagnosis as well. One study of patients with breast cancer, carried out nearly 30 years ago, suggested that denial of diagnosis generally occurs early in a patient’s course of illness and decreases over time, but may arise again in the terminal phase of cancer. Another analysis, evaluating this phenomenon across 13 studies, found that the prevalence of denial at diagnosis ranged from 4% to as high as 47%. 

An oncologist delivers somewhere between 10,000 to 30,000 episodes of bad news over the course of a career, so there’s always a chance that a patient will respond in a way that’s on the “spectrum of disbelief,” said Paul Helft, MD, professor of medicine and recently retired director of the ethics center at Indiana University, Indianapolis.

Diane Meier, MD, said denial and disbelief are natural, protective responses to difficult or frightening news.

When patients exhibit denial, Dr. Meier advises patience and time. Physicians can also ask the patient if there’s a person they trust – a family member or faith leader, for example – who could speak on their behalf about possible next steps.

“The main thing is not to find ourselves in opposition to the patient ... or threaten them with what will happen if they don’t listen to us,” said Dr. Meier, a professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, New York.

And physicians should be careful when they feel themselves wanting to argue with or lecture a patient.

“The minute we feel that urge coming on, that’s a signal to us to stop and realize that something is going on inside the patient that we don’t understand,” she said. “Forcing information on a person who is signaling in every way that they don’t want it and can’t handle it is not a recipe for trust or a high-quality relationship.”
 

Refusing expert advice

Jennifer Lycette, MD, has encountered a growing number of patients who don’t believe their disease should be treated the way she or other oncologists recommend. Some patients remain adamant about sticking with alternative medicine or doing nothing, despite growing sicker.

“I’ve even had situations where the tumor might be visible, like growing through the skin, and people still double down that whatever they’re doing is working,” said Dr. Lycette, a hematologist and medical oncologist at the Providence Seaside Cancer Center in Seaside, Ore.

She encourages these patients to get a second opinion and tries to keep an open mind about alternative approaches. If she’s not familiar with something a patient is considering, she’ll research it with them.

But she makes sure to point out any risks associated with these approaches. While some alternative therapies can support patients through standard treatment, she strongly cautions patients against using these therapies in place of standard treatment.

“The bottom line is to keep the lines of communication open,” she said.

Like Dr. Lycette, Dr. Helft has been encountering more patients with alternative health beliefs who rely on people outside of the medical system for elements of their care.

In the past, he used to tell these patients that science is incomplete, and physicians don’t know everything. But he’s changed his tune.

“I’ve taken to just telling them what I believe, which is that the majority of things that they hear and are being sold are almost certainly ineffective and a waste of money,” he said. “I’ve come to accept that people are adults, and they make their own decisions, and sometimes they make decisions that are not the ones that I would make or want them to make.”
 

Delivering bad news

Dr. Helft often sees patients seeking a second or third opinion on their cancer. These patients may not all be in denial about having cancer, but they typically don’t want to hear bad news, which can make treatment a challenge.

To handle these scenarios, Dr. Helft has developed a system of responses for engaging with patients. He borrows an approach described in 2008 where he acknowledges a patient’s emotional distress and tries to understand why they may not want to know more.

For instance, he might tell a patient: “I have formulated an opinion about your situation, but it sounds as if you have heard many negative descriptions previously. I don’t want to burden you with one more if you don’t feel prepared to talk about it.”

Trying to understand why a patient is resistant to hearing about their condition may also help build trust. “If you could help me understand your thinking about why you would rather not talk about prognosis, it will help me know more about how to discuss other serious issues,” is one approach highlighted in the 2008 guide.

Behind the scenes, Dr. Helft will privately assess how much information about a patient’s prognosis is salient to their decision making, especially if the patient appears to misunderstand their prognosis or if there are various options for treatment over the long-term. 

Dr. Helft will also ask patients how much they want to know. Do they want to discuss no options? A few? All and in detail?

This approach implicitly recognizes that the information is highly stressful but avoids being overly blunt, he notes. It can also help steer patients on the right treatment track and minimize poor decision making.

Samantha Winemaker, MD, a palliative care physician in Hamilton, Ont., finds patients often go through an adjustment period after learning about a new diagnosis. The reaction tends to range from needing time to accept the diagnosis as real to jumping in to understand as much as possible.

Dr. Winemaker, who cohosts “The Waiting Room Revolution” podcast that focuses on helping people deal with a serious illness, encourages physicians to be realistic with patients about their prognosis and deliver news with a dose of gentle truth from the start.

“We should invite patients ‘into the know’ as early as possible, while maintaining hope,” she said.

She calls this approach of balancing hope and reality “walking two roads” and said it extends throughout the illness journey. This way, patients are less likely to be surprised if things make a turn for the worse.

“We should never wait until the 11th hour to give someone bad news,” she said.
 

‘We all want to hope’

Dr. Epstein has listened to hundreds of hours of discussion between doctors and patients as part of his research on communication. He often hears doctors initiate difficult conversations by lecturing a patient.

Many physicians mistakenly believe that, if they say something authoritatively, patients will believe it, he said. But the opposite often happens – patients shut down and instinctively distrust the physician.

Dr. Epstein teaches doctors to establish trust before providing difficult information. Even when a patient expresses outlandish ideas about their illness, treat them with dignity and respect, he advised. “If people don’t feel respected, you don’t have a leg to stand on and there’s no point in trying to convince them.”

Patients and physicians often leave conversations with discordant views of what’s ahead. In one study, two-thirds of patients held wildly different views on their prognosis, compared with their doctors, and most had no idea they were at odds with their physician.

In the past, Dr. Epstein has tried to close the gap between his understanding of a patient’s prognosis and the patient’s. But more recently he has become less convinced of the need to do so.

“What I try to do now is focus more on the uncertainty there,” he said. He uses phrases like: “Given that we don’t know how long you will live, I just need to know what you would want me to do if things took a turn for the worse” or “I’m worried that if you don’t have the surgery, you might experience more pain in the future.”

He urged doctors to pay attention to their word choices. Use care with the phrase “response rate” – patients sometimes mistake this to mean that they are being cured. And, instead of telling patients they “must” do something, he says that he worries about consequences for them if they don’t.

He asks patients what they’re hearing from other people in their lives or online. Sometimes patients say that people close to them are encouraging them to stop medical treatment or pursue alternative therapies. When that happens, Dr. Epstein asks to meet with that person to talk to them about his concerns for their loved one.

He also acknowledges calculated uncertainty often exists in medicine. That, he says, leaves open the potential for exceptional circumstances.

“And we all want to hope,” Dr. Epstein said.

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

In June, Rebecca A. Shatsky, MD, a medical oncologist, turned to Twitter for advice: “What do you do/say when a patient won’t believe you that they have #CANCER. As an oncologist this comes up every now and then and proves very difficult, looking to hear how others have dealt and what works best to help patients here.”

About a dozen people weighed in, offering various thoughts on how to approach these thorny situations. One oncologist suggested revisiting the conversation a few days later, after the patient has more time to process; others suggested sharing the pathology report or images with their patient.

Another person simply noted that “if a [patient] doesn’t want to believe they have cancer, no amount of evidence will change that.”

Based on the initial responses, “it appears there is a paucity of answers sadly,” wrote Dr. Shatsky, a breast cancer specialist at University of California, San Diego.

But for Dr. Shatsky, these incidents spoke to another alarming trend: a rampant mistrust of the medical community that is “becoming MORE common instead of less.”
 

‘Erosion of trust’

Overall, experts say that situations like the one Dr. Shatsky described – patients who don’t believe their cancer diagnosis – occur infrequently.

But denial comes in many forms, and complete disbelief is probably the most extreme. Patients may also downplay the severity of their disease, shy away from hearing bad news, or refuse standard treatment or their doctor’s advice.

Like Dr. Shatsky, these experts say they are also seeing a troubling increase in patients who don’t believe their physicians or don’t trust their recommendations.

“I think there’s an erosion of trust in expertise, in general,” said Ronald M. Epstein, MD, professor of family medicine and psychiatry & oncology at the University of Rochester (N.Y.). “People distrust science more than they did maybe 20 or 30 years ago, or at least that seems to be the case.”

Denial and distrust in cancer care are not new. These responses – along with wishful thinking, distraction, and minimization – are long-established responses among oncology patients. In 1972, Avery D. Weisman, MD, a psychiatrist at Harvard Medical School, Boston, wrote his book “On Dying and Denying,” and ever since, denial and similar responses have been explored in the oncology literature.

Much of this research has focused on the latter stages of illness, but denial can be present at diagnosis as well. One study of patients with breast cancer, carried out nearly 30 years ago, suggested that denial of diagnosis generally occurs early in a patient’s course of illness and decreases over time, but may arise again in the terminal phase of cancer. Another analysis, evaluating this phenomenon across 13 studies, found that the prevalence of denial at diagnosis ranged from 4% to as high as 47%. 

An oncologist delivers somewhere between 10,000 to 30,000 episodes of bad news over the course of a career, so there’s always a chance that a patient will respond in a way that’s on the “spectrum of disbelief,” said Paul Helft, MD, professor of medicine and recently retired director of the ethics center at Indiana University, Indianapolis.

Diane Meier, MD, said denial and disbelief are natural, protective responses to difficult or frightening news.

When patients exhibit denial, Dr. Meier advises patience and time. Physicians can also ask the patient if there’s a person they trust – a family member or faith leader, for example – who could speak on their behalf about possible next steps.

“The main thing is not to find ourselves in opposition to the patient ... or threaten them with what will happen if they don’t listen to us,” said Dr. Meier, a professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, New York.

And physicians should be careful when they feel themselves wanting to argue with or lecture a patient.

“The minute we feel that urge coming on, that’s a signal to us to stop and realize that something is going on inside the patient that we don’t understand,” she said. “Forcing information on a person who is signaling in every way that they don’t want it and can’t handle it is not a recipe for trust or a high-quality relationship.”
 

Refusing expert advice

Jennifer Lycette, MD, has encountered a growing number of patients who don’t believe their disease should be treated the way she or other oncologists recommend. Some patients remain adamant about sticking with alternative medicine or doing nothing, despite growing sicker.

“I’ve even had situations where the tumor might be visible, like growing through the skin, and people still double down that whatever they’re doing is working,” said Dr. Lycette, a hematologist and medical oncologist at the Providence Seaside Cancer Center in Seaside, Ore.

She encourages these patients to get a second opinion and tries to keep an open mind about alternative approaches. If she’s not familiar with something a patient is considering, she’ll research it with them.

But she makes sure to point out any risks associated with these approaches. While some alternative therapies can support patients through standard treatment, she strongly cautions patients against using these therapies in place of standard treatment.

“The bottom line is to keep the lines of communication open,” she said.

Like Dr. Lycette, Dr. Helft has been encountering more patients with alternative health beliefs who rely on people outside of the medical system for elements of their care.

In the past, he used to tell these patients that science is incomplete, and physicians don’t know everything. But he’s changed his tune.

“I’ve taken to just telling them what I believe, which is that the majority of things that they hear and are being sold are almost certainly ineffective and a waste of money,” he said. “I’ve come to accept that people are adults, and they make their own decisions, and sometimes they make decisions that are not the ones that I would make or want them to make.”
 

Delivering bad news

Dr. Helft often sees patients seeking a second or third opinion on their cancer. These patients may not all be in denial about having cancer, but they typically don’t want to hear bad news, which can make treatment a challenge.

To handle these scenarios, Dr. Helft has developed a system of responses for engaging with patients. He borrows an approach described in 2008 where he acknowledges a patient’s emotional distress and tries to understand why they may not want to know more.

For instance, he might tell a patient: “I have formulated an opinion about your situation, but it sounds as if you have heard many negative descriptions previously. I don’t want to burden you with one more if you don’t feel prepared to talk about it.”

Trying to understand why a patient is resistant to hearing about their condition may also help build trust. “If you could help me understand your thinking about why you would rather not talk about prognosis, it will help me know more about how to discuss other serious issues,” is one approach highlighted in the 2008 guide.

Behind the scenes, Dr. Helft will privately assess how much information about a patient’s prognosis is salient to their decision making, especially if the patient appears to misunderstand their prognosis or if there are various options for treatment over the long-term. 

Dr. Helft will also ask patients how much they want to know. Do they want to discuss no options? A few? All and in detail?

This approach implicitly recognizes that the information is highly stressful but avoids being overly blunt, he notes. It can also help steer patients on the right treatment track and minimize poor decision making.

Samantha Winemaker, MD, a palliative care physician in Hamilton, Ont., finds patients often go through an adjustment period after learning about a new diagnosis. The reaction tends to range from needing time to accept the diagnosis as real to jumping in to understand as much as possible.

Dr. Winemaker, who cohosts “The Waiting Room Revolution” podcast that focuses on helping people deal with a serious illness, encourages physicians to be realistic with patients about their prognosis and deliver news with a dose of gentle truth from the start.

“We should invite patients ‘into the know’ as early as possible, while maintaining hope,” she said.

She calls this approach of balancing hope and reality “walking two roads” and said it extends throughout the illness journey. This way, patients are less likely to be surprised if things make a turn for the worse.

“We should never wait until the 11th hour to give someone bad news,” she said.
 

‘We all want to hope’

Dr. Epstein has listened to hundreds of hours of discussion between doctors and patients as part of his research on communication. He often hears doctors initiate difficult conversations by lecturing a patient.

Many physicians mistakenly believe that, if they say something authoritatively, patients will believe it, he said. But the opposite often happens – patients shut down and instinctively distrust the physician.

Dr. Epstein teaches doctors to establish trust before providing difficult information. Even when a patient expresses outlandish ideas about their illness, treat them with dignity and respect, he advised. “If people don’t feel respected, you don’t have a leg to stand on and there’s no point in trying to convince them.”

Patients and physicians often leave conversations with discordant views of what’s ahead. In one study, two-thirds of patients held wildly different views on their prognosis, compared with their doctors, and most had no idea they were at odds with their physician.

In the past, Dr. Epstein has tried to close the gap between his understanding of a patient’s prognosis and the patient’s. But more recently he has become less convinced of the need to do so.

“What I try to do now is focus more on the uncertainty there,” he said. He uses phrases like: “Given that we don’t know how long you will live, I just need to know what you would want me to do if things took a turn for the worse” or “I’m worried that if you don’t have the surgery, you might experience more pain in the future.”

He urged doctors to pay attention to their word choices. Use care with the phrase “response rate” – patients sometimes mistake this to mean that they are being cured. And, instead of telling patients they “must” do something, he says that he worries about consequences for them if they don’t.

He asks patients what they’re hearing from other people in their lives or online. Sometimes patients say that people close to them are encouraging them to stop medical treatment or pursue alternative therapies. When that happens, Dr. Epstein asks to meet with that person to talk to them about his concerns for their loved one.

He also acknowledges calculated uncertainty often exists in medicine. That, he says, leaves open the potential for exceptional circumstances.

“And we all want to hope,” Dr. Epstein said.

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

In June, Rebecca A. Shatsky, MD, a medical oncologist, turned to Twitter for advice: “What do you do/say when a patient won’t believe you that they have #CANCER. As an oncologist this comes up every now and then and proves very difficult, looking to hear how others have dealt and what works best to help patients here.”

About a dozen people weighed in, offering various thoughts on how to approach these thorny situations. One oncologist suggested revisiting the conversation a few days later, after the patient has more time to process; others suggested sharing the pathology report or images with their patient.

Another person simply noted that “if a [patient] doesn’t want to believe they have cancer, no amount of evidence will change that.”

Based on the initial responses, “it appears there is a paucity of answers sadly,” wrote Dr. Shatsky, a breast cancer specialist at University of California, San Diego.

But for Dr. Shatsky, these incidents spoke to another alarming trend: a rampant mistrust of the medical community that is “becoming MORE common instead of less.”
 

‘Erosion of trust’

Overall, experts say that situations like the one Dr. Shatsky described – patients who don’t believe their cancer diagnosis – occur infrequently.

But denial comes in many forms, and complete disbelief is probably the most extreme. Patients may also downplay the severity of their disease, shy away from hearing bad news, or refuse standard treatment or their doctor’s advice.

Like Dr. Shatsky, these experts say they are also seeing a troubling increase in patients who don’t believe their physicians or don’t trust their recommendations.

“I think there’s an erosion of trust in expertise, in general,” said Ronald M. Epstein, MD, professor of family medicine and psychiatry & oncology at the University of Rochester (N.Y.). “People distrust science more than they did maybe 20 or 30 years ago, or at least that seems to be the case.”

Denial and distrust in cancer care are not new. These responses – along with wishful thinking, distraction, and minimization – are long-established responses among oncology patients. In 1972, Avery D. Weisman, MD, a psychiatrist at Harvard Medical School, Boston, wrote his book “On Dying and Denying,” and ever since, denial and similar responses have been explored in the oncology literature.

Much of this research has focused on the latter stages of illness, but denial can be present at diagnosis as well. One study of patients with breast cancer, carried out nearly 30 years ago, suggested that denial of diagnosis generally occurs early in a patient’s course of illness and decreases over time, but may arise again in the terminal phase of cancer. Another analysis, evaluating this phenomenon across 13 studies, found that the prevalence of denial at diagnosis ranged from 4% to as high as 47%. 

An oncologist delivers somewhere between 10,000 to 30,000 episodes of bad news over the course of a career, so there’s always a chance that a patient will respond in a way that’s on the “spectrum of disbelief,” said Paul Helft, MD, professor of medicine and recently retired director of the ethics center at Indiana University, Indianapolis.

Diane Meier, MD, said denial and disbelief are natural, protective responses to difficult or frightening news.

When patients exhibit denial, Dr. Meier advises patience and time. Physicians can also ask the patient if there’s a person they trust – a family member or faith leader, for example – who could speak on their behalf about possible next steps.

“The main thing is not to find ourselves in opposition to the patient ... or threaten them with what will happen if they don’t listen to us,” said Dr. Meier, a professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, New York.

And physicians should be careful when they feel themselves wanting to argue with or lecture a patient.

“The minute we feel that urge coming on, that’s a signal to us to stop and realize that something is going on inside the patient that we don’t understand,” she said. “Forcing information on a person who is signaling in every way that they don’t want it and can’t handle it is not a recipe for trust or a high-quality relationship.”
 

Refusing expert advice

Jennifer Lycette, MD, has encountered a growing number of patients who don’t believe their disease should be treated the way she or other oncologists recommend. Some patients remain adamant about sticking with alternative medicine or doing nothing, despite growing sicker.

“I’ve even had situations where the tumor might be visible, like growing through the skin, and people still double down that whatever they’re doing is working,” said Dr. Lycette, a hematologist and medical oncologist at the Providence Seaside Cancer Center in Seaside, Ore.

She encourages these patients to get a second opinion and tries to keep an open mind about alternative approaches. If she’s not familiar with something a patient is considering, she’ll research it with them.

But she makes sure to point out any risks associated with these approaches. While some alternative therapies can support patients through standard treatment, she strongly cautions patients against using these therapies in place of standard treatment.

“The bottom line is to keep the lines of communication open,” she said.

Like Dr. Lycette, Dr. Helft has been encountering more patients with alternative health beliefs who rely on people outside of the medical system for elements of their care.

In the past, he used to tell these patients that science is incomplete, and physicians don’t know everything. But he’s changed his tune.

“I’ve taken to just telling them what I believe, which is that the majority of things that they hear and are being sold are almost certainly ineffective and a waste of money,” he said. “I’ve come to accept that people are adults, and they make their own decisions, and sometimes they make decisions that are not the ones that I would make or want them to make.”
 

Delivering bad news

Dr. Helft often sees patients seeking a second or third opinion on their cancer. These patients may not all be in denial about having cancer, but they typically don’t want to hear bad news, which can make treatment a challenge.

To handle these scenarios, Dr. Helft has developed a system of responses for engaging with patients. He borrows an approach described in 2008 where he acknowledges a patient’s emotional distress and tries to understand why they may not want to know more.

For instance, he might tell a patient: “I have formulated an opinion about your situation, but it sounds as if you have heard many negative descriptions previously. I don’t want to burden you with one more if you don’t feel prepared to talk about it.”

Trying to understand why a patient is resistant to hearing about their condition may also help build trust. “If you could help me understand your thinking about why you would rather not talk about prognosis, it will help me know more about how to discuss other serious issues,” is one approach highlighted in the 2008 guide.

Behind the scenes, Dr. Helft will privately assess how much information about a patient’s prognosis is salient to their decision making, especially if the patient appears to misunderstand their prognosis or if there are various options for treatment over the long-term. 

Dr. Helft will also ask patients how much they want to know. Do they want to discuss no options? A few? All and in detail?

This approach implicitly recognizes that the information is highly stressful but avoids being overly blunt, he notes. It can also help steer patients on the right treatment track and minimize poor decision making.

Samantha Winemaker, MD, a palliative care physician in Hamilton, Ont., finds patients often go through an adjustment period after learning about a new diagnosis. The reaction tends to range from needing time to accept the diagnosis as real to jumping in to understand as much as possible.

Dr. Winemaker, who cohosts “The Waiting Room Revolution” podcast that focuses on helping people deal with a serious illness, encourages physicians to be realistic with patients about their prognosis and deliver news with a dose of gentle truth from the start.

“We should invite patients ‘into the know’ as early as possible, while maintaining hope,” she said.

She calls this approach of balancing hope and reality “walking two roads” and said it extends throughout the illness journey. This way, patients are less likely to be surprised if things make a turn for the worse.

“We should never wait until the 11th hour to give someone bad news,” she said.
 

‘We all want to hope’

Dr. Epstein has listened to hundreds of hours of discussion between doctors and patients as part of his research on communication. He often hears doctors initiate difficult conversations by lecturing a patient.

Many physicians mistakenly believe that, if they say something authoritatively, patients will believe it, he said. But the opposite often happens – patients shut down and instinctively distrust the physician.

Dr. Epstein teaches doctors to establish trust before providing difficult information. Even when a patient expresses outlandish ideas about their illness, treat them with dignity and respect, he advised. “If people don’t feel respected, you don’t have a leg to stand on and there’s no point in trying to convince them.”

Patients and physicians often leave conversations with discordant views of what’s ahead. In one study, two-thirds of patients held wildly different views on their prognosis, compared with their doctors, and most had no idea they were at odds with their physician.

In the past, Dr. Epstein has tried to close the gap between his understanding of a patient’s prognosis and the patient’s. But more recently he has become less convinced of the need to do so.

“What I try to do now is focus more on the uncertainty there,” he said. He uses phrases like: “Given that we don’t know how long you will live, I just need to know what you would want me to do if things took a turn for the worse” or “I’m worried that if you don’t have the surgery, you might experience more pain in the future.”

He urged doctors to pay attention to their word choices. Use care with the phrase “response rate” – patients sometimes mistake this to mean that they are being cured. And, instead of telling patients they “must” do something, he says that he worries about consequences for them if they don’t.

He asks patients what they’re hearing from other people in their lives or online. Sometimes patients say that people close to them are encouraging them to stop medical treatment or pursue alternative therapies. When that happens, Dr. Epstein asks to meet with that person to talk to them about his concerns for their loved one.

He also acknowledges calculated uncertainty often exists in medicine. That, he says, leaves open the potential for exceptional circumstances.

“And we all want to hope,” Dr. Epstein said.

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

Six years ago, Kim Bowles had a double mastectomy after being diagnosed with stage 3 breast cancer. Instead of opting for reconstruction, she decided to go “flat.” At 35, she had already breast fed both of her children, and didn’t want breasts anymore.

She asked her surgeon for an aesthetic flat closure, showing him photos of a smooth chest with no excess skin flaps. Although he agreed to her request in the office, he reneged in the operating room.

As the anesthesia took effect he said, “I’ll just leave a little extra skin, in case you change your mind.”

The last thing she remembers is telling him “no.”

When Ms. Bowles woke up, she saw excess tissue instead of the smooth chest she had requested. When she was eventually well enough, she staged a topless sit-in at the hospital and marched outside with a placard, baring her breastless, disfigured chest.

“Do I need a B-cup side-boob?” she asked, pulling at her lateral excess tissue, often referred to as dog ears. “You would never think that a surgeon would leave somebody looking like that,” she said in an interview.

Based on her experience, Ms. Bowles coined the term “flat denial” to describe what her surgeon did.
 

The weight of flat denial

In a recent study, Deanna Attai, MD, a breast surgeon at University of California, Los Angeles, discovered that more than one in five women who want a flat closure experience flat denial.

But well before that survey, Dr. Attai first came across flat denial more than a decade ago when a patient came to her for a second opinion after another surgeon insisted the patient see a psychiatrist when she requested a flat closure. Dr. Attai performed the flat closure for her instead.

But Dr. Attai said flat denial can take many forms. Some experiences may closely match the paternalistic encounter Ms. Bowles had, where a surgeon disregards a patient’s request. Other surgeons may simply be ignorant that a flat closure can be achieved aesthetically or that patients would even want this option.

This resistance aligns with Hester Schnipper’s experience as an oncology social worker. In her 45-year career, she has often found herself pushing back against breast surgeons who present reconstruction as if it were the only option for patients after mastectomy.

“And because most women are so overwhelmed, so scared, so stressed, they tend to go with whatever the doctor suggests,” said Ms. Schnipper.

Whatever form flat denial takes, the outcome can be damaging to the patient.

“This isn’t just ‘my scar’s a little thick.’ This is much more,” Dr. Attai said. “How do you even put a prosthesis on that? And if you’re not going to do a prosthesis in a bra, how do you even wear a shirt with all of that? It becomes a cleaning issue and depending on how things scar down you can get irregular fibrosis.”

What’s more, the harms of flat denial can extend beyond the physical scars.

Like Ms. Bowles, Anne Marie Champagne had made her desire for a flat closure clear to her surgeon before undergoing a mastectomy in 2009. The surgeon also reneged in the operating room while Champagne was unconscious and unable to object.

Ms. Champagne told The Washington Post that her surgeon’s justification for his actions left her feeling “profound grief, a combination of heartache and anger.

“I couldn’t believe that my surgeon would make a decision for me while I was under anesthesia that went against everything we had discussed – what I had consented to.”

Although it’s not clear how often women experience flat denial, discussions surrounding the issue have increased in recent years.

Ms. Bowles started a patient advocacy organization called “Not Putting on A Shirt” to help other women. And Dr. Attai moderates a Twitter group, called #BCSM or Breast Cancer Social Media, where patients share their experiences of breast cancer treatment, including in some cases flat denial.

“In getting to know so many women in the online space, an early observation was that the conversations online were different than what we had in the office,” Dr. Attai said. Online, “women were less guarded and more open about sharing the entirety of their breast cancer experience, including the more painful and raw moments.”

Being immersed in these moments, it also became clear to Dr. Attai that members of the treatment team don’t always recognize what is most important to a patient. “We might not ask, we might not allow them the time to express their preferences, or we might not really hear them,” she said.
 

An evolving awareness

National figures on the prevalence of flat closures remain elusive, but it has always been an option. And data indicate that many women choose no reconstruction after mastectomy.

One U.S. survey of women undergoing mastectomy between 2005 and 2007 found that 58% opted not to receive reconstruction, and a more recent British National Mastectomy and Breast Reconstruction Audit from 2011 found 70% chose no reconstruction.

“I definitely have seen more patients requesting to go flat after mastectomy, likely as they feel more empowered to make this decision,” Roshni Rao, MD, chief of breast surgery at Columbia University Medical Center, New York, told The Washington Post.

But to better understand the scope of flat denial, Dr. Attai and colleagues conducted a survey, published in Annals of Surgical Oncology. In it, she found that, among 931 women who had opted to go flat after mastectomy, 22% had experienced flat denial. That meant not being offered the option of going flat, not being supported in their choice to go flat, or not receiving the flat closure surgery initially agreed upon.

In the spring of 2022, Dr. Attai, past president of the American Society of Breast Surgeons, took her results to the society’s annual meeting. The goal was to bring to light aesthetic flat closure techniques as well as the harms of flat denial, presenting photos of the sagging, shriveled skin flaps alongside her analysis.

“No one ever goes into an operation intending it to look like those horrible pictures,” she said.

Asking for “no breast mound reconstruction” should imply a nice neat flat closure, or an aesthetic flat closure, Dr. Attai explained. “A patient should not have to specify she wants the surgeon to make all efforts to remove redundant and excess skin and fat, but I do think having the discussion and making preferences very clear is important, especially as we’ve seen that some patients are not getting the desired outcome.”

To help improve education and communication, the board of “No Putting on a Shirt” also had an exhibitor’s booth focused on aesthetic flat closures at the ASBrS meeting.

And given this growing awareness, the National Accreditation Program for Breast Centers has begun asking breast centers to report their process for shared decision-making on postmastectomy choices and provide proof that patients’ closure choices are being heard and followed.
 

A shift toward aesthetics

Despite a growing interest in flat closure aesthetics, the landscape shift is still relatively new.

The traditional mastectomy training Dr. Attai and colleagues went through in the 1990s did not emphasize aesthetics.

“I just removed the breast and then I left the room,” she said, explaining that the plastic surgeon took charge of the reconstruction. “We never really learned how to make a nice, neat closure.”

Abhishek Chatterjee, MD, MBA, a breast surgical oncologist and board-certified plastic surgeon, agreed that aesthetics have become more central in the field.

“A decade ago, I would argue that ... it wasn’t in the training program,” but today breast surgery fellowships now include “flat closures that are aesthetically appropriate,” said Dr. Chatterjee, who works at Tufts Medical Center in Boston and is vice chair of the ASBrS oncoplastics committee.

“In my mind, and in any surgeon’s mind, when you do something, you have to do it well ... and with that, aesthetics should be presumed,” he added.

But the term “aesthetic flat closure” was only adopted by the National Cancer Institute in 2020. The NCI, which considers an aesthetic flat closure reconstructive not cosmetic surgery, defines it as rebuilding the shape of the chest wall after breasts are removed, and involves contouring and eliminating excess tissue to create a smooth, flat chest wall.

Achieving this smooth look requires a skilled surgeon trained in flat closure reconstruction, which is not necessarily a guarantee. To help women find a surgeon, “Not Putting on A Shirt” has a flat friendly directory where patients can recommend surgeons who provide aesthetic flat closures. As of August 2022, the list has now grown to over 300 surgeons.

Dr. Chatterjee said the ASBrS is actively involved in training surgeons in aesthetic flat closure. Given this shift, he said most general or breast surgeons should have the skill set to design mastectomy flaps that enable a flat closure with no excess skin, but there are some caveats.

For instance, he noted, if a woman has a lot of breast tissue and excess skin in the outer, lateral folds of the axilla, “it is very, very hard to get a flat closure” and in those rare circumstances, a breast surgeon may need assistance from a plastic surgeon.

But Dr. Attai found a significant gap still exists between what should be done and what is being done in practice.

Part of that disconnect may stem from the lack of a standard of care.

In a recent publication, a team of plastic surgeons from New York University noted that, to date, “there is no plastic surgery literature on specific techniques to achieve an aesthetic flat closure after mastectomy.”

And Dr. Attai added, “there is really no way to know at this point what women are getting when they choose no breast mound reconstruction.”

Physicians may also simply not understand what their patients want.

Dr. Attai said she was “blown away” by the reaction to her presentation on flat denial at ASBrS in April. “I had a lot of members come up to me afterwards and say ‘I had no idea that patients would want this. I am guilty of not offering this.’ ”

In addition, Dr. Chatterjee said, patients may now have “much higher” expectations for a smooth, symmetrical look “versus an outcome with excess skin and bumps.”

But Ms. Bowles said the desire for a more aesthetically pleasing look is nothing new.

“Women have always cared about how they look, they are just shamed into accepting a lesser result,” she argued. “If you look at why women go flat, the primary reason is they don’t want more surgery, not ‘I don’t care what I look like.’ ”

Three years after the mastectomy that left flaps of skin hanging from her chest, Ms. Bowles finally had a revision surgery to achieve the flat closure aesthetic she had wanted from the get-go.

“Nobody expects perfection, but I think the important thing is to have a standard of care that’s optimal,” said Ms. Bowles. “A patient like me should not have needed another surgery.”

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

Six years ago, Kim Bowles had a double mastectomy after being diagnosed with stage 3 breast cancer. Instead of opting for reconstruction, she decided to go “flat.” At 35, she had already breast fed both of her children, and didn’t want breasts anymore.

She asked her surgeon for an aesthetic flat closure, showing him photos of a smooth chest with no excess skin flaps. Although he agreed to her request in the office, he reneged in the operating room.

As the anesthesia took effect he said, “I’ll just leave a little extra skin, in case you change your mind.”

The last thing she remembers is telling him “no.”

When Ms. Bowles woke up, she saw excess tissue instead of the smooth chest she had requested. When she was eventually well enough, she staged a topless sit-in at the hospital and marched outside with a placard, baring her breastless, disfigured chest.

“Do I need a B-cup side-boob?” she asked, pulling at her lateral excess tissue, often referred to as dog ears. “You would never think that a surgeon would leave somebody looking like that,” she said in an interview.

Based on her experience, Ms. Bowles coined the term “flat denial” to describe what her surgeon did.
 

The weight of flat denial

In a recent study, Deanna Attai, MD, a breast surgeon at University of California, Los Angeles, discovered that more than one in five women who want a flat closure experience flat denial.

But well before that survey, Dr. Attai first came across flat denial more than a decade ago when a patient came to her for a second opinion after another surgeon insisted the patient see a psychiatrist when she requested a flat closure. Dr. Attai performed the flat closure for her instead.

But Dr. Attai said flat denial can take many forms. Some experiences may closely match the paternalistic encounter Ms. Bowles had, where a surgeon disregards a patient’s request. Other surgeons may simply be ignorant that a flat closure can be achieved aesthetically or that patients would even want this option.

This resistance aligns with Hester Schnipper’s experience as an oncology social worker. In her 45-year career, she has often found herself pushing back against breast surgeons who present reconstruction as if it were the only option for patients after mastectomy.

“And because most women are so overwhelmed, so scared, so stressed, they tend to go with whatever the doctor suggests,” said Ms. Schnipper.

Whatever form flat denial takes, the outcome can be damaging to the patient.

“This isn’t just ‘my scar’s a little thick.’ This is much more,” Dr. Attai said. “How do you even put a prosthesis on that? And if you’re not going to do a prosthesis in a bra, how do you even wear a shirt with all of that? It becomes a cleaning issue and depending on how things scar down you can get irregular fibrosis.”

What’s more, the harms of flat denial can extend beyond the physical scars.

Like Ms. Bowles, Anne Marie Champagne had made her desire for a flat closure clear to her surgeon before undergoing a mastectomy in 2009. The surgeon also reneged in the operating room while Champagne was unconscious and unable to object.

Ms. Champagne told The Washington Post that her surgeon’s justification for his actions left her feeling “profound grief, a combination of heartache and anger.

“I couldn’t believe that my surgeon would make a decision for me while I was under anesthesia that went against everything we had discussed – what I had consented to.”

Although it’s not clear how often women experience flat denial, discussions surrounding the issue have increased in recent years.

Ms. Bowles started a patient advocacy organization called “Not Putting on A Shirt” to help other women. And Dr. Attai moderates a Twitter group, called #BCSM or Breast Cancer Social Media, where patients share their experiences of breast cancer treatment, including in some cases flat denial.

“In getting to know so many women in the online space, an early observation was that the conversations online were different than what we had in the office,” Dr. Attai said. Online, “women were less guarded and more open about sharing the entirety of their breast cancer experience, including the more painful and raw moments.”

Being immersed in these moments, it also became clear to Dr. Attai that members of the treatment team don’t always recognize what is most important to a patient. “We might not ask, we might not allow them the time to express their preferences, or we might not really hear them,” she said.
 

An evolving awareness

National figures on the prevalence of flat closures remain elusive, but it has always been an option. And data indicate that many women choose no reconstruction after mastectomy.

One U.S. survey of women undergoing mastectomy between 2005 and 2007 found that 58% opted not to receive reconstruction, and a more recent British National Mastectomy and Breast Reconstruction Audit from 2011 found 70% chose no reconstruction.

“I definitely have seen more patients requesting to go flat after mastectomy, likely as they feel more empowered to make this decision,” Roshni Rao, MD, chief of breast surgery at Columbia University Medical Center, New York, told The Washington Post.

But to better understand the scope of flat denial, Dr. Attai and colleagues conducted a survey, published in Annals of Surgical Oncology. In it, she found that, among 931 women who had opted to go flat after mastectomy, 22% had experienced flat denial. That meant not being offered the option of going flat, not being supported in their choice to go flat, or not receiving the flat closure surgery initially agreed upon.

In the spring of 2022, Dr. Attai, past president of the American Society of Breast Surgeons, took her results to the society’s annual meeting. The goal was to bring to light aesthetic flat closure techniques as well as the harms of flat denial, presenting photos of the sagging, shriveled skin flaps alongside her analysis.

“No one ever goes into an operation intending it to look like those horrible pictures,” she said.

Asking for “no breast mound reconstruction” should imply a nice neat flat closure, or an aesthetic flat closure, Dr. Attai explained. “A patient should not have to specify she wants the surgeon to make all efforts to remove redundant and excess skin and fat, but I do think having the discussion and making preferences very clear is important, especially as we’ve seen that some patients are not getting the desired outcome.”

To help improve education and communication, the board of “No Putting on a Shirt” also had an exhibitor’s booth focused on aesthetic flat closures at the ASBrS meeting.

And given this growing awareness, the National Accreditation Program for Breast Centers has begun asking breast centers to report their process for shared decision-making on postmastectomy choices and provide proof that patients’ closure choices are being heard and followed.
 

A shift toward aesthetics

Despite a growing interest in flat closure aesthetics, the landscape shift is still relatively new.

The traditional mastectomy training Dr. Attai and colleagues went through in the 1990s did not emphasize aesthetics.

“I just removed the breast and then I left the room,” she said, explaining that the plastic surgeon took charge of the reconstruction. “We never really learned how to make a nice, neat closure.”

Abhishek Chatterjee, MD, MBA, a breast surgical oncologist and board-certified plastic surgeon, agreed that aesthetics have become more central in the field.

“A decade ago, I would argue that ... it wasn’t in the training program,” but today breast surgery fellowships now include “flat closures that are aesthetically appropriate,” said Dr. Chatterjee, who works at Tufts Medical Center in Boston and is vice chair of the ASBrS oncoplastics committee.

“In my mind, and in any surgeon’s mind, when you do something, you have to do it well ... and with that, aesthetics should be presumed,” he added.

But the term “aesthetic flat closure” was only adopted by the National Cancer Institute in 2020. The NCI, which considers an aesthetic flat closure reconstructive not cosmetic surgery, defines it as rebuilding the shape of the chest wall after breasts are removed, and involves contouring and eliminating excess tissue to create a smooth, flat chest wall.

Achieving this smooth look requires a skilled surgeon trained in flat closure reconstruction, which is not necessarily a guarantee. To help women find a surgeon, “Not Putting on A Shirt” has a flat friendly directory where patients can recommend surgeons who provide aesthetic flat closures. As of August 2022, the list has now grown to over 300 surgeons.

Dr. Chatterjee said the ASBrS is actively involved in training surgeons in aesthetic flat closure. Given this shift, he said most general or breast surgeons should have the skill set to design mastectomy flaps that enable a flat closure with no excess skin, but there are some caveats.

For instance, he noted, if a woman has a lot of breast tissue and excess skin in the outer, lateral folds of the axilla, “it is very, very hard to get a flat closure” and in those rare circumstances, a breast surgeon may need assistance from a plastic surgeon.

But Dr. Attai found a significant gap still exists between what should be done and what is being done in practice.

Part of that disconnect may stem from the lack of a standard of care.

In a recent publication, a team of plastic surgeons from New York University noted that, to date, “there is no plastic surgery literature on specific techniques to achieve an aesthetic flat closure after mastectomy.”

And Dr. Attai added, “there is really no way to know at this point what women are getting when they choose no breast mound reconstruction.”

Physicians may also simply not understand what their patients want.

Dr. Attai said she was “blown away” by the reaction to her presentation on flat denial at ASBrS in April. “I had a lot of members come up to me afterwards and say ‘I had no idea that patients would want this. I am guilty of not offering this.’ ”

In addition, Dr. Chatterjee said, patients may now have “much higher” expectations for a smooth, symmetrical look “versus an outcome with excess skin and bumps.”

But Ms. Bowles said the desire for a more aesthetically pleasing look is nothing new.

“Women have always cared about how they look, they are just shamed into accepting a lesser result,” she argued. “If you look at why women go flat, the primary reason is they don’t want more surgery, not ‘I don’t care what I look like.’ ”

Three years after the mastectomy that left flaps of skin hanging from her chest, Ms. Bowles finally had a revision surgery to achieve the flat closure aesthetic she had wanted from the get-go.

“Nobody expects perfection, but I think the important thing is to have a standard of care that’s optimal,” said Ms. Bowles. “A patient like me should not have needed another surgery.”

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

Six years ago, Kim Bowles had a double mastectomy after being diagnosed with stage 3 breast cancer. Instead of opting for reconstruction, she decided to go “flat.” At 35, she had already breast fed both of her children, and didn’t want breasts anymore.

She asked her surgeon for an aesthetic flat closure, showing him photos of a smooth chest with no excess skin flaps. Although he agreed to her request in the office, he reneged in the operating room.

As the anesthesia took effect he said, “I’ll just leave a little extra skin, in case you change your mind.”

The last thing she remembers is telling him “no.”

When Ms. Bowles woke up, she saw excess tissue instead of the smooth chest she had requested. When she was eventually well enough, she staged a topless sit-in at the hospital and marched outside with a placard, baring her breastless, disfigured chest.

“Do I need a B-cup side-boob?” she asked, pulling at her lateral excess tissue, often referred to as dog ears. “You would never think that a surgeon would leave somebody looking like that,” she said in an interview.

Based on her experience, Ms. Bowles coined the term “flat denial” to describe what her surgeon did.
 

The weight of flat denial

In a recent study, Deanna Attai, MD, a breast surgeon at University of California, Los Angeles, discovered that more than one in five women who want a flat closure experience flat denial.

But well before that survey, Dr. Attai first came across flat denial more than a decade ago when a patient came to her for a second opinion after another surgeon insisted the patient see a psychiatrist when she requested a flat closure. Dr. Attai performed the flat closure for her instead.

But Dr. Attai said flat denial can take many forms. Some experiences may closely match the paternalistic encounter Ms. Bowles had, where a surgeon disregards a patient’s request. Other surgeons may simply be ignorant that a flat closure can be achieved aesthetically or that patients would even want this option.

This resistance aligns with Hester Schnipper’s experience as an oncology social worker. In her 45-year career, she has often found herself pushing back against breast surgeons who present reconstruction as if it were the only option for patients after mastectomy.

“And because most women are so overwhelmed, so scared, so stressed, they tend to go with whatever the doctor suggests,” said Ms. Schnipper.

Whatever form flat denial takes, the outcome can be damaging to the patient.

“This isn’t just ‘my scar’s a little thick.’ This is much more,” Dr. Attai said. “How do you even put a prosthesis on that? And if you’re not going to do a prosthesis in a bra, how do you even wear a shirt with all of that? It becomes a cleaning issue and depending on how things scar down you can get irregular fibrosis.”

What’s more, the harms of flat denial can extend beyond the physical scars.

Like Ms. Bowles, Anne Marie Champagne had made her desire for a flat closure clear to her surgeon before undergoing a mastectomy in 2009. The surgeon also reneged in the operating room while Champagne was unconscious and unable to object.

Ms. Champagne told The Washington Post that her surgeon’s justification for his actions left her feeling “profound grief, a combination of heartache and anger.

“I couldn’t believe that my surgeon would make a decision for me while I was under anesthesia that went against everything we had discussed – what I had consented to.”

Although it’s not clear how often women experience flat denial, discussions surrounding the issue have increased in recent years.

Ms. Bowles started a patient advocacy organization called “Not Putting on A Shirt” to help other women. And Dr. Attai moderates a Twitter group, called #BCSM or Breast Cancer Social Media, where patients share their experiences of breast cancer treatment, including in some cases flat denial.

“In getting to know so many women in the online space, an early observation was that the conversations online were different than what we had in the office,” Dr. Attai said. Online, “women were less guarded and more open about sharing the entirety of their breast cancer experience, including the more painful and raw moments.”

Being immersed in these moments, it also became clear to Dr. Attai that members of the treatment team don’t always recognize what is most important to a patient. “We might not ask, we might not allow them the time to express their preferences, or we might not really hear them,” she said.
 

An evolving awareness

National figures on the prevalence of flat closures remain elusive, but it has always been an option. And data indicate that many women choose no reconstruction after mastectomy.

One U.S. survey of women undergoing mastectomy between 2005 and 2007 found that 58% opted not to receive reconstruction, and a more recent British National Mastectomy and Breast Reconstruction Audit from 2011 found 70% chose no reconstruction.

“I definitely have seen more patients requesting to go flat after mastectomy, likely as they feel more empowered to make this decision,” Roshni Rao, MD, chief of breast surgery at Columbia University Medical Center, New York, told The Washington Post.

But to better understand the scope of flat denial, Dr. Attai and colleagues conducted a survey, published in Annals of Surgical Oncology. In it, she found that, among 931 women who had opted to go flat after mastectomy, 22% had experienced flat denial. That meant not being offered the option of going flat, not being supported in their choice to go flat, or not receiving the flat closure surgery initially agreed upon.

In the spring of 2022, Dr. Attai, past president of the American Society of Breast Surgeons, took her results to the society’s annual meeting. The goal was to bring to light aesthetic flat closure techniques as well as the harms of flat denial, presenting photos of the sagging, shriveled skin flaps alongside her analysis.

“No one ever goes into an operation intending it to look like those horrible pictures,” she said.

Asking for “no breast mound reconstruction” should imply a nice neat flat closure, or an aesthetic flat closure, Dr. Attai explained. “A patient should not have to specify she wants the surgeon to make all efforts to remove redundant and excess skin and fat, but I do think having the discussion and making preferences very clear is important, especially as we’ve seen that some patients are not getting the desired outcome.”

To help improve education and communication, the board of “No Putting on a Shirt” also had an exhibitor’s booth focused on aesthetic flat closures at the ASBrS meeting.

And given this growing awareness, the National Accreditation Program for Breast Centers has begun asking breast centers to report their process for shared decision-making on postmastectomy choices and provide proof that patients’ closure choices are being heard and followed.
 

A shift toward aesthetics

Despite a growing interest in flat closure aesthetics, the landscape shift is still relatively new.

The traditional mastectomy training Dr. Attai and colleagues went through in the 1990s did not emphasize aesthetics.

“I just removed the breast and then I left the room,” she said, explaining that the plastic surgeon took charge of the reconstruction. “We never really learned how to make a nice, neat closure.”

Abhishek Chatterjee, MD, MBA, a breast surgical oncologist and board-certified plastic surgeon, agreed that aesthetics have become more central in the field.

“A decade ago, I would argue that ... it wasn’t in the training program,” but today breast surgery fellowships now include “flat closures that are aesthetically appropriate,” said Dr. Chatterjee, who works at Tufts Medical Center in Boston and is vice chair of the ASBrS oncoplastics committee.

“In my mind, and in any surgeon’s mind, when you do something, you have to do it well ... and with that, aesthetics should be presumed,” he added.

But the term “aesthetic flat closure” was only adopted by the National Cancer Institute in 2020. The NCI, which considers an aesthetic flat closure reconstructive not cosmetic surgery, defines it as rebuilding the shape of the chest wall after breasts are removed, and involves contouring and eliminating excess tissue to create a smooth, flat chest wall.

Achieving this smooth look requires a skilled surgeon trained in flat closure reconstruction, which is not necessarily a guarantee. To help women find a surgeon, “Not Putting on A Shirt” has a flat friendly directory where patients can recommend surgeons who provide aesthetic flat closures. As of August 2022, the list has now grown to over 300 surgeons.

Dr. Chatterjee said the ASBrS is actively involved in training surgeons in aesthetic flat closure. Given this shift, he said most general or breast surgeons should have the skill set to design mastectomy flaps that enable a flat closure with no excess skin, but there are some caveats.

For instance, he noted, if a woman has a lot of breast tissue and excess skin in the outer, lateral folds of the axilla, “it is very, very hard to get a flat closure” and in those rare circumstances, a breast surgeon may need assistance from a plastic surgeon.

But Dr. Attai found a significant gap still exists between what should be done and what is being done in practice.

Part of that disconnect may stem from the lack of a standard of care.

In a recent publication, a team of plastic surgeons from New York University noted that, to date, “there is no plastic surgery literature on specific techniques to achieve an aesthetic flat closure after mastectomy.”

And Dr. Attai added, “there is really no way to know at this point what women are getting when they choose no breast mound reconstruction.”

Physicians may also simply not understand what their patients want.

Dr. Attai said she was “blown away” by the reaction to her presentation on flat denial at ASBrS in April. “I had a lot of members come up to me afterwards and say ‘I had no idea that patients would want this. I am guilty of not offering this.’ ”

In addition, Dr. Chatterjee said, patients may now have “much higher” expectations for a smooth, symmetrical look “versus an outcome with excess skin and bumps.”

But Ms. Bowles said the desire for a more aesthetically pleasing look is nothing new.

“Women have always cared about how they look, they are just shamed into accepting a lesser result,” she argued. “If you look at why women go flat, the primary reason is they don’t want more surgery, not ‘I don’t care what I look like.’ ”

Three years after the mastectomy that left flaps of skin hanging from her chest, Ms. Bowles finally had a revision surgery to achieve the flat closure aesthetic she had wanted from the get-go.

“Nobody expects perfection, but I think the important thing is to have a standard of care that’s optimal,” said Ms. Bowles. “A patient like me should not have needed another surgery.”

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

Despite significant disruptions to the health care system and employment early in the COVID-19 pandemic, the uninsured rate among cancer survivors remained stable in 2020, new research indicates.

In addition, the prevalence of unhealthy behaviors, including smoking and poor sleep habits, appeared to decline among cancer survivors as well as adults who had no history of cancer during this period.

“Our findings suggest that the pandemic may have motivated people to adopt certain healthier behaviors,” Xuesong Han, PhD, American Cancer Society, Atlanta, said in a statement. In addition, policies implemented in response to the pandemic regarding insurance coverage, unemployment benefits, and financial assistance “may have contributed to the observed positive changes.”

Dr. Han and colleagues noted that “to the best of our knowledge, our study provides the first nationally representative estimates of the effects of the first year of the COVID-19 pandemic on cancer survivors in the United States.”

The study was published online in Cancer.

Given the considerable upheaval caused by the COVID-19 pandemic, Dr. Han and colleagues wanted to explore how cancer survivors, in particular, were affected during the first year.

The analysis included 57,132 cancer survivors and 1,044,585 adults without cancer who were involved in the Behavioral Risk Factor Surveillance System.

The researchers found that the unemployment rate in 2020 increased by 43% among cancer survivors and by 57% among adults without a cancer history compared with the previous 2 years.

However, the rate of uninsured cancer survivors aged 18-64 years remained relatively stable in 2020 at 8%, compared with 8.8% in 2017-2019.

Notably, the prevalence of insufficient sleep decreased among cancer survivors (43% to 39%), as did smoking (22% to 19%). Among adults without a history of cancer, there was a decline in insufficient sleep (37% to 34.3%) and smoking (16% to 15%). The prevalence of binge drinking decreased among adults with and those without a history of cancer as well.

Obesity rates, however, increased during the first year of the pandemic among cancer survivors (36.5% to 40%) as well as among those with no cancer history (30.8% to 32.7%). In addition, more adults without a cancer history reported an increase in mental distress in 2020 compared with before the COVID-19 pandemic.

The authors suggest that some of the positive trends observed could be explained, in part, by increased enrollment in the Affordable Care Act and by the Families First Coronavirus Response Act, which increased the federal government’s share of Medicaid costs and prevented states from terminating Medicaid coverage during the pandemic.

“These provisions likely compensated for the loss in employer-sponsored insurance,” the authors noted.

But, they added, “as policies related to the public health emergency expire, ongoing monitoring of long-term effects of the COVID-19 pandemic on cancer survivorship is warranted.”

Dr. Han has received a grant from AstraZeneca outside of the current study.

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

Despite significant disruptions to the health care system and employment early in the COVID-19 pandemic, the uninsured rate among cancer survivors remained stable in 2020, new research indicates.

In addition, the prevalence of unhealthy behaviors, including smoking and poor sleep habits, appeared to decline among cancer survivors as well as adults who had no history of cancer during this period.

“Our findings suggest that the pandemic may have motivated people to adopt certain healthier behaviors,” Xuesong Han, PhD, American Cancer Society, Atlanta, said in a statement. In addition, policies implemented in response to the pandemic regarding insurance coverage, unemployment benefits, and financial assistance “may have contributed to the observed positive changes.”

Dr. Han and colleagues noted that “to the best of our knowledge, our study provides the first nationally representative estimates of the effects of the first year of the COVID-19 pandemic on cancer survivors in the United States.”

The study was published online in Cancer.

Given the considerable upheaval caused by the COVID-19 pandemic, Dr. Han and colleagues wanted to explore how cancer survivors, in particular, were affected during the first year.

The analysis included 57,132 cancer survivors and 1,044,585 adults without cancer who were involved in the Behavioral Risk Factor Surveillance System.

The researchers found that the unemployment rate in 2020 increased by 43% among cancer survivors and by 57% among adults without a cancer history compared with the previous 2 years.

However, the rate of uninsured cancer survivors aged 18-64 years remained relatively stable in 2020 at 8%, compared with 8.8% in 2017-2019.

Notably, the prevalence of insufficient sleep decreased among cancer survivors (43% to 39%), as did smoking (22% to 19%). Among adults without a history of cancer, there was a decline in insufficient sleep (37% to 34.3%) and smoking (16% to 15%). The prevalence of binge drinking decreased among adults with and those without a history of cancer as well.

Obesity rates, however, increased during the first year of the pandemic among cancer survivors (36.5% to 40%) as well as among those with no cancer history (30.8% to 32.7%). In addition, more adults without a cancer history reported an increase in mental distress in 2020 compared with before the COVID-19 pandemic.

The authors suggest that some of the positive trends observed could be explained, in part, by increased enrollment in the Affordable Care Act and by the Families First Coronavirus Response Act, which increased the federal government’s share of Medicaid costs and prevented states from terminating Medicaid coverage during the pandemic.

“These provisions likely compensated for the loss in employer-sponsored insurance,” the authors noted.

But, they added, “as policies related to the public health emergency expire, ongoing monitoring of long-term effects of the COVID-19 pandemic on cancer survivorship is warranted.”

Dr. Han has received a grant from AstraZeneca outside of the current study.

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

Despite significant disruptions to the health care system and employment early in the COVID-19 pandemic, the uninsured rate among cancer survivors remained stable in 2020, new research indicates.

In addition, the prevalence of unhealthy behaviors, including smoking and poor sleep habits, appeared to decline among cancer survivors as well as adults who had no history of cancer during this period.

“Our findings suggest that the pandemic may have motivated people to adopt certain healthier behaviors,” Xuesong Han, PhD, American Cancer Society, Atlanta, said in a statement. In addition, policies implemented in response to the pandemic regarding insurance coverage, unemployment benefits, and financial assistance “may have contributed to the observed positive changes.”

Dr. Han and colleagues noted that “to the best of our knowledge, our study provides the first nationally representative estimates of the effects of the first year of the COVID-19 pandemic on cancer survivors in the United States.”

The study was published online in Cancer.

Given the considerable upheaval caused by the COVID-19 pandemic, Dr. Han and colleagues wanted to explore how cancer survivors, in particular, were affected during the first year.

The analysis included 57,132 cancer survivors and 1,044,585 adults without cancer who were involved in the Behavioral Risk Factor Surveillance System.

The researchers found that the unemployment rate in 2020 increased by 43% among cancer survivors and by 57% among adults without a cancer history compared with the previous 2 years.

However, the rate of uninsured cancer survivors aged 18-64 years remained relatively stable in 2020 at 8%, compared with 8.8% in 2017-2019.

Notably, the prevalence of insufficient sleep decreased among cancer survivors (43% to 39%), as did smoking (22% to 19%). Among adults without a history of cancer, there was a decline in insufficient sleep (37% to 34.3%) and smoking (16% to 15%). The prevalence of binge drinking decreased among adults with and those without a history of cancer as well.

Obesity rates, however, increased during the first year of the pandemic among cancer survivors (36.5% to 40%) as well as among those with no cancer history (30.8% to 32.7%). In addition, more adults without a cancer history reported an increase in mental distress in 2020 compared with before the COVID-19 pandemic.

The authors suggest that some of the positive trends observed could be explained, in part, by increased enrollment in the Affordable Care Act and by the Families First Coronavirus Response Act, which increased the federal government’s share of Medicaid costs and prevented states from terminating Medicaid coverage during the pandemic.

“These provisions likely compensated for the loss in employer-sponsored insurance,” the authors noted.

But, they added, “as policies related to the public health emergency expire, ongoing monitoring of long-term effects of the COVID-19 pandemic on cancer survivorship is warranted.”

Dr. Han has received a grant from AstraZeneca outside of the current study.

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

Alcohol is a major preventable risk factor for cancer. New data suggest that reducing alcohol intake reduces the risk of developing an alcohol-related cancer.

The findings, from a large population-based study conducted in Korea, underscore the importance of encouraging individuals to quit drinking or to reduce alcohol consumption to help reduce cancer risk, the authors noted.

The study was published online in JAMA Network Open.

It provides evidence “suggesting that cancer risk can be meaningfully altered by changing the amount of alcoholic beverages consumed,” wrote the authors of an accompanying editorial, Neal D. Freedman, PhD, and Christian C. Abnet, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

“Alcohol consumption is an important cancer risk factor,” they wrote, adding that a “well examined dose-response association has been reported, with highest risks observed among people who drink 3 alcoholic beverages per day and higher.”

The new study shows that a “reduction in use was associated with lower risk, particularly among participants who started drinking at a heavy level,” they noted.

Previous studies have estimated that alcohol use accounts for nearly 4% of newly diagnosed cancers worldwide and nearly 5% of U.S. cancer cases overall.

But the figures are much higher for some specific cancers. That same U.S. study found that alcohol accounts for at least 45% of oral cavity/pharyngeal cancers and at least 25% of laryngeal cancers, as well as 12.1% of female breast cancers, 11.1% of colorectal cancers, 10.5% of liver cancers, and 7.7% of esophageal cancers, as previously reported by this news organization.
 

New findings on reducing intake

This latest study involved an analysis of data on 4.5 million individuals who were adult beneficiaries of the Korean National Health Insurance Service. The median age of the participants was 53.6 years, and they underwent a national health screening in 2009 and 2011.

During median follow-up of 6.4 years, the cancer incidence rate was 7.7 per 1,000 person-years.

Information on alcohol consumption was collected from self-administered questionnaires completed during the health screenings. Participants were categorized on the basis of alcohol consumption: none (0 g/d), mild ( less than 15 g/d), moderate (15-29.9 g/d), and heavy (30 or more g/d).

Compared with those who sustained their alcohol consumption level during the study period, those who increased their level were at higher risk of alcohol-related cancers and all cancers, the investigators found.

The increase in alcohol-related cancer incidence was dose dependent: Those who changed from nondrinking to mild, moderate, or heavy drinking were at increasingly higher risk for alcohol-related cancer, compared with those who remained nondrinkers (adjusted hazard ratios [aHRs], 1.03, 1.10, and 1.34, respectively).

Participants who were mild drinkers at baseline and who quit drinking were at lower risk of alcohol-related cancer, compared with those whose drinking level was sustained (aHR, 0.96). Those with moderate or heavy drinking levels who quit drinking were at higher overall cancer risk than were those who sustained their drinking levels. However, this difference was negated when quitting was sustained, the authors noted.

For heavy drinkers who reduced their drinking levels, cancer incidence was reduced, compared with those who sustained heavy drinking levels. This was true for those who changed from heavy to moderate drinking (aHR, 0.91 for alcohol-related cancers; 0.96 for alcohol-related cancers) and those who changed from heavy to mild drinking (aHR, 0.92 for alcohol-related cancers and all cancers).

“Alcohol cessation and reduction should be reinforced for the prevention of cancer,” concluded the authors.
 

Implications and future directions

The editorialists noted that the study is limited by several factors, such as a short interval between assessments and relatively short follow-up. There is also no information on participants’ alcohol consumption earlier in life or about other healthy lifestyle changes during the study period. In addition, there is no mention of a genetic variant affecting aldehyde dehydrogenase that leads to alcohol-induced flushing, which is common among East Asians.

Despite of these limitations, the study provides “important new findings about the potential role of changes in alcohol consumption in cancer risk,” Dr. Freedman and Dr. Abnet noted. Future studies should examine the association between alcohol intake and cancer risk in other populations and use longer intervals between assessments, they suggested.

“Such studies are needed to move the field forward and inform public health guidance on cancer prevention,” the editorialists concluded.

The authors of the study and the editorialists have disclosed no relevant financial relationships.

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

Alcohol is a major preventable risk factor for cancer. New data suggest that reducing alcohol intake reduces the risk of developing an alcohol-related cancer.

The findings, from a large population-based study conducted in Korea, underscore the importance of encouraging individuals to quit drinking or to reduce alcohol consumption to help reduce cancer risk, the authors noted.

The study was published online in JAMA Network Open.

It provides evidence “suggesting that cancer risk can be meaningfully altered by changing the amount of alcoholic beverages consumed,” wrote the authors of an accompanying editorial, Neal D. Freedman, PhD, and Christian C. Abnet, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

“Alcohol consumption is an important cancer risk factor,” they wrote, adding that a “well examined dose-response association has been reported, with highest risks observed among people who drink 3 alcoholic beverages per day and higher.”

The new study shows that a “reduction in use was associated with lower risk, particularly among participants who started drinking at a heavy level,” they noted.

Previous studies have estimated that alcohol use accounts for nearly 4% of newly diagnosed cancers worldwide and nearly 5% of U.S. cancer cases overall.

But the figures are much higher for some specific cancers. That same U.S. study found that alcohol accounts for at least 45% of oral cavity/pharyngeal cancers and at least 25% of laryngeal cancers, as well as 12.1% of female breast cancers, 11.1% of colorectal cancers, 10.5% of liver cancers, and 7.7% of esophageal cancers, as previously reported by this news organization.
 

New findings on reducing intake

This latest study involved an analysis of data on 4.5 million individuals who were adult beneficiaries of the Korean National Health Insurance Service. The median age of the participants was 53.6 years, and they underwent a national health screening in 2009 and 2011.

During median follow-up of 6.4 years, the cancer incidence rate was 7.7 per 1,000 person-years.

Information on alcohol consumption was collected from self-administered questionnaires completed during the health screenings. Participants were categorized on the basis of alcohol consumption: none (0 g/d), mild ( less than 15 g/d), moderate (15-29.9 g/d), and heavy (30 or more g/d).

Compared with those who sustained their alcohol consumption level during the study period, those who increased their level were at higher risk of alcohol-related cancers and all cancers, the investigators found.

The increase in alcohol-related cancer incidence was dose dependent: Those who changed from nondrinking to mild, moderate, or heavy drinking were at increasingly higher risk for alcohol-related cancer, compared with those who remained nondrinkers (adjusted hazard ratios [aHRs], 1.03, 1.10, and 1.34, respectively).

Participants who were mild drinkers at baseline and who quit drinking were at lower risk of alcohol-related cancer, compared with those whose drinking level was sustained (aHR, 0.96). Those with moderate or heavy drinking levels who quit drinking were at higher overall cancer risk than were those who sustained their drinking levels. However, this difference was negated when quitting was sustained, the authors noted.

For heavy drinkers who reduced their drinking levels, cancer incidence was reduced, compared with those who sustained heavy drinking levels. This was true for those who changed from heavy to moderate drinking (aHR, 0.91 for alcohol-related cancers; 0.96 for alcohol-related cancers) and those who changed from heavy to mild drinking (aHR, 0.92 for alcohol-related cancers and all cancers).

“Alcohol cessation and reduction should be reinforced for the prevention of cancer,” concluded the authors.
 

Implications and future directions

The editorialists noted that the study is limited by several factors, such as a short interval between assessments and relatively short follow-up. There is also no information on participants’ alcohol consumption earlier in life or about other healthy lifestyle changes during the study period. In addition, there is no mention of a genetic variant affecting aldehyde dehydrogenase that leads to alcohol-induced flushing, which is common among East Asians.

Despite of these limitations, the study provides “important new findings about the potential role of changes in alcohol consumption in cancer risk,” Dr. Freedman and Dr. Abnet noted. Future studies should examine the association between alcohol intake and cancer risk in other populations and use longer intervals between assessments, they suggested.

“Such studies are needed to move the field forward and inform public health guidance on cancer prevention,” the editorialists concluded.

The authors of the study and the editorialists have disclosed no relevant financial relationships.

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

Alcohol is a major preventable risk factor for cancer. New data suggest that reducing alcohol intake reduces the risk of developing an alcohol-related cancer.

The findings, from a large population-based study conducted in Korea, underscore the importance of encouraging individuals to quit drinking or to reduce alcohol consumption to help reduce cancer risk, the authors noted.

The study was published online in JAMA Network Open.

It provides evidence “suggesting that cancer risk can be meaningfully altered by changing the amount of alcoholic beverages consumed,” wrote the authors of an accompanying editorial, Neal D. Freedman, PhD, and Christian C. Abnet, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

“Alcohol consumption is an important cancer risk factor,” they wrote, adding that a “well examined dose-response association has been reported, with highest risks observed among people who drink 3 alcoholic beverages per day and higher.”

The new study shows that a “reduction in use was associated with lower risk, particularly among participants who started drinking at a heavy level,” they noted.

Previous studies have estimated that alcohol use accounts for nearly 4% of newly diagnosed cancers worldwide and nearly 5% of U.S. cancer cases overall.

But the figures are much higher for some specific cancers. That same U.S. study found that alcohol accounts for at least 45% of oral cavity/pharyngeal cancers and at least 25% of laryngeal cancers, as well as 12.1% of female breast cancers, 11.1% of colorectal cancers, 10.5% of liver cancers, and 7.7% of esophageal cancers, as previously reported by this news organization.
 

New findings on reducing intake

This latest study involved an analysis of data on 4.5 million individuals who were adult beneficiaries of the Korean National Health Insurance Service. The median age of the participants was 53.6 years, and they underwent a national health screening in 2009 and 2011.

During median follow-up of 6.4 years, the cancer incidence rate was 7.7 per 1,000 person-years.

Information on alcohol consumption was collected from self-administered questionnaires completed during the health screenings. Participants were categorized on the basis of alcohol consumption: none (0 g/d), mild ( less than 15 g/d), moderate (15-29.9 g/d), and heavy (30 or more g/d).

Compared with those who sustained their alcohol consumption level during the study period, those who increased their level were at higher risk of alcohol-related cancers and all cancers, the investigators found.

The increase in alcohol-related cancer incidence was dose dependent: Those who changed from nondrinking to mild, moderate, or heavy drinking were at increasingly higher risk for alcohol-related cancer, compared with those who remained nondrinkers (adjusted hazard ratios [aHRs], 1.03, 1.10, and 1.34, respectively).

Participants who were mild drinkers at baseline and who quit drinking were at lower risk of alcohol-related cancer, compared with those whose drinking level was sustained (aHR, 0.96). Those with moderate or heavy drinking levels who quit drinking were at higher overall cancer risk than were those who sustained their drinking levels. However, this difference was negated when quitting was sustained, the authors noted.

For heavy drinkers who reduced their drinking levels, cancer incidence was reduced, compared with those who sustained heavy drinking levels. This was true for those who changed from heavy to moderate drinking (aHR, 0.91 for alcohol-related cancers; 0.96 for alcohol-related cancers) and those who changed from heavy to mild drinking (aHR, 0.92 for alcohol-related cancers and all cancers).

“Alcohol cessation and reduction should be reinforced for the prevention of cancer,” concluded the authors.
 

Implications and future directions

The editorialists noted that the study is limited by several factors, such as a short interval between assessments and relatively short follow-up. There is also no information on participants’ alcohol consumption earlier in life or about other healthy lifestyle changes during the study period. In addition, there is no mention of a genetic variant affecting aldehyde dehydrogenase that leads to alcohol-induced flushing, which is common among East Asians.

Despite of these limitations, the study provides “important new findings about the potential role of changes in alcohol consumption in cancer risk,” Dr. Freedman and Dr. Abnet noted. Future studies should examine the association between alcohol intake and cancer risk in other populations and use longer intervals between assessments, they suggested.

“Such studies are needed to move the field forward and inform public health guidance on cancer prevention,” the editorialists concluded.

The authors of the study and the editorialists have disclosed no relevant financial relationships.

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

Use of the epidermal growth-factor receptor inhibitor erlotinib led to about a 30% reduction in duodenal polyp burden after 6 months of once-weekly treatment for patients with familial adenomatous polyposis (FAP) in a phase 2 clinical trial.

“If existing data are confirmed and extended through future research, this strategy has the potential for substantial impact on clinical practice by decreasing, delaying, or augmenting endoscopic and surgical interventions as the mainstay for duodenal cancer prevention in this high-risk patient population,” the study team says.

FAP is a rare genetic condition that markedly raises the risk for colorectal polyps and cancer.

“The biological pathway that leads to the development of polyps and colon cancer in patients with FAP is the same biological pathway as patients in the general population,” study investigator Niloy Jewel Samadder, MD, with the Mayo Clinic, Rochester, Minn., said in a news release.

“Our trial looked at opportunities to use chemoprevention agents in patients with FAP to inhibit the development of precancerous polyps in the small bowel and colorectum,” Dr. Samadder explains.

In an earlier study, the researchers found that the combination of the COX-2 inhibitor sulindac (150 mg twice daily) and erlotinib (75 mg daily) reduced duodenal polyp burden.

However, the dual-drug strategy was associated with a relatively high adverse event (AE) rate, which may limit use of the combination for chemoprevention, as reported previously.

This phase 2 study tested whether erlotinib’s AE profile would be improved with a once-weekly dosing schedule while still reducing polyp burden.

The study was first published online in the journal Gut.

In the single-arm, multicenter study, 46 adults with FAP (mean age, 44 years; 48% women) self-administered 350 mg of erlotinib by mouth one time per week for 6 months. All but four participants completed the 6-month study.

After 6 months of weekly erlotinib, duodenal polyp burden was significantly reduced, with a mean percent reduction of 29.6% (95% confidence interval: –39.6% to –19.7%; P < .0001).

The benefit was observed in patients with either Spigelman 2 or Spigelman 3 duodenal polyp burden.

“Though only 12% of patients noted a decrease in Spigelman stage from 3 to 2 associated with therapy, the majority of patients (86%) had stable disease while on treatment,” the study team reports.

GI polyp number (a secondary outcome) was also decreased after 6 months of treatment with erlotinib (median decrease of 30.8%; P = .0256).

While once-weekly erlotinib was “generally” well tolerated, grade 2 or 3 AEs were reported in 72% of patients; two suffered grade 3 toxicity. Nonetheless, the AE rate was significantly more than the expected null hypothesis rate of 50%, the study team states.

Four patients withdrew from the study because of drug-induced AEs, which included grade 3 rash acneiform, grade 2 infections (hand, foot, and mouth disease), grade 1 fatigue, and grade 1 rash acneiform. No grade 4 AEs were reported.

The most common AE was an erlotinib-induced acneiform-like rash, which occurred in 56.5% of study patients. The rash was managed with topical cortisone and/or clindamycin. Additional erlotinib-induced AEs included oral mucositis (6.5%), diarrhea (50%), and nausea (26.1%).

Summing up, Dr. Samadder and colleagues note that FAP “portends a heritable, systemic predisposition to cancer, and the ultimate goal of cancer preventive intervention is to interrupt the development of neoplasia, need for surgery, and ultimately death from cancer, with an acceptable AE profile.”

The findings from this phase 2 trial support further study of erlotinib as “an effective, acceptable cancer preventive agent for FAP-associated gastrointestinal polyposis,” they conclude.

The study was sponsored by the National Cancer Institute. Dr. Samadder is a consultant for Janssen Research and Development, Recursion Pharmaceuticals, and Cancer Prevention Pharmaceuticals.

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

Use of the epidermal growth-factor receptor inhibitor erlotinib led to about a 30% reduction in duodenal polyp burden after 6 months of once-weekly treatment for patients with familial adenomatous polyposis (FAP) in a phase 2 clinical trial.

“If existing data are confirmed and extended through future research, this strategy has the potential for substantial impact on clinical practice by decreasing, delaying, or augmenting endoscopic and surgical interventions as the mainstay for duodenal cancer prevention in this high-risk patient population,” the study team says.

FAP is a rare genetic condition that markedly raises the risk for colorectal polyps and cancer.

“The biological pathway that leads to the development of polyps and colon cancer in patients with FAP is the same biological pathway as patients in the general population,” study investigator Niloy Jewel Samadder, MD, with the Mayo Clinic, Rochester, Minn., said in a news release.

“Our trial looked at opportunities to use chemoprevention agents in patients with FAP to inhibit the development of precancerous polyps in the small bowel and colorectum,” Dr. Samadder explains.

In an earlier study, the researchers found that the combination of the COX-2 inhibitor sulindac (150 mg twice daily) and erlotinib (75 mg daily) reduced duodenal polyp burden.

However, the dual-drug strategy was associated with a relatively high adverse event (AE) rate, which may limit use of the combination for chemoprevention, as reported previously.

This phase 2 study tested whether erlotinib’s AE profile would be improved with a once-weekly dosing schedule while still reducing polyp burden.

The study was first published online in the journal Gut.

In the single-arm, multicenter study, 46 adults with FAP (mean age, 44 years; 48% women) self-administered 350 mg of erlotinib by mouth one time per week for 6 months. All but four participants completed the 6-month study.

After 6 months of weekly erlotinib, duodenal polyp burden was significantly reduced, with a mean percent reduction of 29.6% (95% confidence interval: –39.6% to –19.7%; P < .0001).

The benefit was observed in patients with either Spigelman 2 or Spigelman 3 duodenal polyp burden.

“Though only 12% of patients noted a decrease in Spigelman stage from 3 to 2 associated with therapy, the majority of patients (86%) had stable disease while on treatment,” the study team reports.

GI polyp number (a secondary outcome) was also decreased after 6 months of treatment with erlotinib (median decrease of 30.8%; P = .0256).

While once-weekly erlotinib was “generally” well tolerated, grade 2 or 3 AEs were reported in 72% of patients; two suffered grade 3 toxicity. Nonetheless, the AE rate was significantly more than the expected null hypothesis rate of 50%, the study team states.

Four patients withdrew from the study because of drug-induced AEs, which included grade 3 rash acneiform, grade 2 infections (hand, foot, and mouth disease), grade 1 fatigue, and grade 1 rash acneiform. No grade 4 AEs were reported.

The most common AE was an erlotinib-induced acneiform-like rash, which occurred in 56.5% of study patients. The rash was managed with topical cortisone and/or clindamycin. Additional erlotinib-induced AEs included oral mucositis (6.5%), diarrhea (50%), and nausea (26.1%).

Summing up, Dr. Samadder and colleagues note that FAP “portends a heritable, systemic predisposition to cancer, and the ultimate goal of cancer preventive intervention is to interrupt the development of neoplasia, need for surgery, and ultimately death from cancer, with an acceptable AE profile.”

The findings from this phase 2 trial support further study of erlotinib as “an effective, acceptable cancer preventive agent for FAP-associated gastrointestinal polyposis,” they conclude.

The study was sponsored by the National Cancer Institute. Dr. Samadder is a consultant for Janssen Research and Development, Recursion Pharmaceuticals, and Cancer Prevention Pharmaceuticals.

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

Use of the epidermal growth-factor receptor inhibitor erlotinib led to about a 30% reduction in duodenal polyp burden after 6 months of once-weekly treatment for patients with familial adenomatous polyposis (FAP) in a phase 2 clinical trial.

“If existing data are confirmed and extended through future research, this strategy has the potential for substantial impact on clinical practice by decreasing, delaying, or augmenting endoscopic and surgical interventions as the mainstay for duodenal cancer prevention in this high-risk patient population,” the study team says.

FAP is a rare genetic condition that markedly raises the risk for colorectal polyps and cancer.

“The biological pathway that leads to the development of polyps and colon cancer in patients with FAP is the same biological pathway as patients in the general population,” study investigator Niloy Jewel Samadder, MD, with the Mayo Clinic, Rochester, Minn., said in a news release.

“Our trial looked at opportunities to use chemoprevention agents in patients with FAP to inhibit the development of precancerous polyps in the small bowel and colorectum,” Dr. Samadder explains.

In an earlier study, the researchers found that the combination of the COX-2 inhibitor sulindac (150 mg twice daily) and erlotinib (75 mg daily) reduced duodenal polyp burden.

However, the dual-drug strategy was associated with a relatively high adverse event (AE) rate, which may limit use of the combination for chemoprevention, as reported previously.

This phase 2 study tested whether erlotinib’s AE profile would be improved with a once-weekly dosing schedule while still reducing polyp burden.

The study was first published online in the journal Gut.

In the single-arm, multicenter study, 46 adults with FAP (mean age, 44 years; 48% women) self-administered 350 mg of erlotinib by mouth one time per week for 6 months. All but four participants completed the 6-month study.

After 6 months of weekly erlotinib, duodenal polyp burden was significantly reduced, with a mean percent reduction of 29.6% (95% confidence interval: –39.6% to –19.7%; P < .0001).

The benefit was observed in patients with either Spigelman 2 or Spigelman 3 duodenal polyp burden.

“Though only 12% of patients noted a decrease in Spigelman stage from 3 to 2 associated with therapy, the majority of patients (86%) had stable disease while on treatment,” the study team reports.

GI polyp number (a secondary outcome) was also decreased after 6 months of treatment with erlotinib (median decrease of 30.8%; P = .0256).

While once-weekly erlotinib was “generally” well tolerated, grade 2 or 3 AEs were reported in 72% of patients; two suffered grade 3 toxicity. Nonetheless, the AE rate was significantly more than the expected null hypothesis rate of 50%, the study team states.

Four patients withdrew from the study because of drug-induced AEs, which included grade 3 rash acneiform, grade 2 infections (hand, foot, and mouth disease), grade 1 fatigue, and grade 1 rash acneiform. No grade 4 AEs were reported.

The most common AE was an erlotinib-induced acneiform-like rash, which occurred in 56.5% of study patients. The rash was managed with topical cortisone and/or clindamycin. Additional erlotinib-induced AEs included oral mucositis (6.5%), diarrhea (50%), and nausea (26.1%).

Summing up, Dr. Samadder and colleagues note that FAP “portends a heritable, systemic predisposition to cancer, and the ultimate goal of cancer preventive intervention is to interrupt the development of neoplasia, need for surgery, and ultimately death from cancer, with an acceptable AE profile.”

The findings from this phase 2 trial support further study of erlotinib as “an effective, acceptable cancer preventive agent for FAP-associated gastrointestinal polyposis,” they conclude.

The study was sponsored by the National Cancer Institute. Dr. Samadder is a consultant for Janssen Research and Development, Recursion Pharmaceuticals, and Cancer Prevention Pharmaceuticals.

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

Gender differences in patient satisfaction with medical care have been evaluated in multiple settings; however, studies specific to the unique population of women veterans with cancer are lacking. Women are reported to value privacy, psychosocial support, and communication to a higher degree compared with men.¹ Factors affecting satisfaction include the following: discomfort in sharing treatment rooms with the opposite gender, a desire for privacy with treatment and restroom use, anatomic or illness differences, and a personal history of abuse^.2-4 Regrettably, up to 1 in 3 women in the United States are victims of sexual trauma in their lifetimes, and up to 1 in 4 women in the military are victims of military sexual trauma. Incidence in both settings is suspected to be higher due to underreporting^.5,6

Chemotherapy treatment units are often uniquely designed as an open space, with several patients sharing a treatment area. The design reduces isolation and facilitates quick nurse-patient access during potentially toxic treatments known to have frequent adverse effects. Data suggest that nursing staff prefer open models to facilitate quick patient assessments and interventions as needed; however, patients and families prefer private treatment rooms, especially among women patients or those receiving longer infusions.⁷

The Veterans Health Administration (VHA) patient population is male predominant, comprised only of 10% female patients.8 Although the proportion of female patients in the VHA is expected to rise annually to about 16% by 2043, the low percentage of female veterans will persist for the foreseeable future.⁸ This low percentage of female veterans is reflected in the Veterans Affairs Portland Health Care System (VAPHCS) cancer patient population and in the use of the chemotherapy infusion unit, which is used for the ambulatory treatment of veterans undergoing cancer therapy.

The VHA has previously explored gender differences in health care, such as with cardiovascular disease, transgender care, and access to mental health.^9-11 However, to the best of our knowledge, no analysis has explored gender differences within the outpatient cancer treatment experience. Patient satisfaction with outpatient cancer care may be magnified in the VHA setting due to the uniquely unequal gender populations, shared treatment space design, and high incidence of sexual abuse among women veterans. Given this, we aimed to identify gender-related preferences in outpatient cancer care in our chemotherapy infusion unit.

In our study, we used the terms male and female to reflect statistical data from the literature or labeled data from the electronic health record (EHR); whereas the terms men and women were used to describe and encompass the cultural implications and context of gender.¹²

Methods

This study was designated as a quality improvement (QI) project by the VAPHCS research office and Institutional Review Board in accordance with VHA policies.

The VAPHCS outpatient chemotherapy infusion unit is designed with 6 rooms for chemotherapy administration. One room is a large open space with 6 chairs for patients. The other rooms are smaller with glass dividers between the rooms, and 3 chairs inside each for patients. There are 2 private bathrooms, each gender neutral. Direct patient care is provided by physicians, nurse practitioners (NPs), infusion unit nurses, and nurse coordinators. Men represent the majority of hematology and oncology physicians (13 of 20 total: 5 women fellow physicians and 2 women attending physicians), and 2 of 4 NPs. Women represent 10 of 12 infusion unit and cancer coordinator nurses. We used the VHA Computerized Patient Record System (CPRS) EHR, to create a list of veterans treated at the VAPHCS outpatient chemotherapy infusion unit for a 2-year period (January 1, 2018, to December 31, 2020).

Male and female patient lists were first generated based on CPRS categorization. We identified all female veterans treated in the ambulatory infusion unit during the study period. Male patients were then chosen at random, recording the most recent names for each year until a matched number per year compared with the female cohort was reached. Patients were recorded only once even though they had multiple infusion unit visits. Patients were excluded who were deceased, on hospice care, lost to follow-up, could not be reached by phone, refused to take the survey, had undeliverable email addresses, or lacked internet or email access.

After filing the appropriate request through the VAPHCS Institutional Review Board committee in January 2021, patient records were reviewed for demographics data, contact information, and infusion treatment history. The survey was then conducted over a 2-week period during January and February 2021. Each patient was invited by phone to complete a 25-question anonymous online survey. The survey questions were created from patient-relayed experiences, then modeled into survey questions in a format similar to other patient satisfaction questionnaires described in cancer care and gender differences.^2,13,14 The survey included self-identification of gender and was multiple choice for all except 2 questions, which allowed an open-ended response (Appendix). Only 1 answer per question was permitted. Only 1 survey link was sent to each veteran who gave permission for the survey. To protect anonymity for the small patient population, we excluded those identifying as gender nonbinary or transgender.

Statistical Analysis

Patient, disease, and treatment features are separated by male and female cohorts to reflect information from the EHR (Table 1). Survey percentages were calculated to reflect the affirmative response of the question asked (Table 2). Questions with answer options of not important, minimally important, important, or very important were calculated to reflect the sum of any importance in both cohorts. Questions with answer options of never, once, often, or every time were calculated to reflect any occurrence (sum of once, often, or every time) in both patient groups. Questions with answer options of strongly agree, somewhat agree, somewhat disagree, and strongly disagree were calculated to reflect any agreement (somewhat agree and strongly agree summed together) for both groups. Comparisons between cohorts were then conducted using a Fisher exact test. A Welch t test was used to calculate the significance of the continuous variable and overall ranking of the infusion unit experience between groups.

Results 

In 2020, 414 individual patients were treated at the VAPAHCS outpatient infusion unit. Of these, 23 (5.6%) were female, and 18 agreed to take the survey. After deceased and duplicate names from 2020 were removed, another 14 eligible 2019 female patients were invited and 6 agreed to participate; 6 eligible 2018 female patients were invited and 4 agreed to take the survey (Figure). Thirty female veterans were sent a survey link and 21 (70%) responses were collected. Twenty-one male 2020 patients were contacted and 18 agreed to take the survey. After removing duplicate names and deceased individuals, 17 of 21 eligible 2019 male patients and 4 of 6 eligible 2018 patients agreed to take the survey. Five additional male veterans declined the online-based survey method. In total, 39 male veterans were reached who agreed to have the survey link emailed, and 20 (51%) total responses were collected.

Most respondents answered all questions in the survey. The most frequently skipped questions included 3 questions that were contingent on a yes answer to a prior question, and 2 openended questions asking for a write-in response. Percentages for female and male respondents were adjusted for number of responses when applicable.

Thirteen (62%) female patients were aged < 65 years, while 18 (90%) of male patients were aged ≥ 65 years. Education beyond high school was reported in 20 female and 15 male respondents. Almost all treatment administered in the infusion unit was for cancer-directed treatment, with only 1 reporting a noncancer treatment (IV iron). The most common malignancy among female patients was breast cancer (n = 11, 52%); for male patients prostate cancer (n = 4, 20%) and hematologic malignancy (n = 4, 20%) were most common. Four (19%) female and 8 (40%) male respondents reported having a metastatic diagnosis. Overall patient satisfaction ranked high with an average score of 9.1 on a 10-point scale. The mean (SD) satisfaction score for female respondents was 1 point lower than that for men: 8.7 (2.2) vs 9.6 (0.6) in men (P = .11).

Eighteen (86%) women reported a history of sexual abuse or harassment compared with 2 (10%) men (P < .001). The sexual abuse assailant was a different gender for 17 of 18 female respondents and of the same gender for both male respondents. Of those with sexual abuse history, 4 women reported feeling uncomfortable around their assailant’s gender vs no men (P = .11), but this difference was not statistically significant. Six women (29%) and 2 (10%) men reported feeling uncomfortable during clinical examinations from comments made by the clinician or during treatment administration (P = .24). Six (29%) women and no men reported that they “felt uncomfortable in the infusion unit by other patients” (P = .02). Six (29%) women and no men reported feeling unable to “voice uncomfortable experiences” to the infusion unit clinician (P = .02).

Ten (48%) women and 6 (30%) men reported emotional support when receiving treatments provided by staff of the same gender (P = .34). Eight (38%) women and 4 (20%) men noted that access to treatment with the same gender was important (P = .31). Six (29%) women and 4 (20%) men indicated that access to a sex or gender-specific restroom was important (P = .72). No gender preferences were identified in the survey questions regarding importance of private treatment room access and level of emotional support when receiving treatment with others of the same malignancy. These relationships were not statistically significant.

In addition, 2 open-ended questions were asked. Seventeen women and 14 men responded. Contact the corresponding author for more information on the questions and responses.

Discussion

Overall patient satisfaction was high among the men and women veterans with cancer who received treatment in our outpatient infusion unit; however, notable gender differences existed. Three items in the survey revealed statistically significant differences in the patient experience between men and women veterans: history of sexual abuse or harassment, uncomfortable feelings among other patients, and discomfort in relaying uncomfortable feelings to a clinician. Other items in the survey did not reach statistical significance; however, we have included discussion of the findings as they may highlight important trends and be of clinical significance.

We suspect differences among genders in patient satisfaction to be related to the high incidence of sexual abuse or harassment history reported by women, much higher at 86% than the one-third to one-fourth incidence rates estimated by the existing literature for civilian or military sexual abuse in women.5,6 These high sexual abuse or harassment rates are present in a majority of women who receive cancer-directed treatment toward a gender-specific breast malignancy, surrounded predominantly among men in a shared treatment space. Together, these factors are likely key reasons behind the differences in satisfaction observed. This sentiment is expressed in our cohort, where one-fifth of women with a sexual abuse or harassment history continue to remain uncomfortable around men, and 29% of women reporting some uncomfortable feelings during their treatment experience compared with none of the men. Additionally, 6 (29%) women vs no men felt uncomfortable in reporting an uncomfortable experience with a clinician; this represents a significant barrier in providing care for these patients.

A key gender preference among women included access to shared treatment rooms with other women and that sharing a treatment space with other women resulted in feeling more emotional support during treatments. Access to gender-specific restrooms was also preferred by women more than men. Key findings in both genders were that about half of men and women valued access to a private treatment room and would derive more emotional support when surrounded by others with the same cancer.

Prior studies on gender and patient satisfaction in general medical care and cancer care have found women value privacy more than men.^1-3 Wessels and colleagues performed an analysis of 386 patients with cancer in Europe and found gender to be the strongest influence in patient preferences within cancer care. Specifically, the highest statically significant association in care preferences among women included privacy, support/counseling/rehabilitation access, and decreased wait times.2 These findings were most pronounced in those with breast cancer compared with other malignancy type and highlights that malignancy type and gender predominance impact care satisfaction.

Traditionally a shared treatment space design has been used in outpatient chemotherapy units, similar to the design of the VAPHCS. However, recent data report on the patient preference for a private treatment space, which was especially prominent among women and those receiving longer infusions.7 In another study that evaluated 225 patients with cancer preferences in sharing a treatment space with those of a different sexual orientation or gender identify, differences were found. Both men and women had a similar level of comfort in sharing a treatment room with someone of a different sexual orientation; however, more women reported discomfort in sharing a treatment space with a transgender woman compared with men who felt more comfortable sharing a space with a transgender man.4 We noted a gender preference may be present to explain the difference. Within our cohort, women valued access to treatment with other women and derived more emotional support when with other women; however, we did not inquire about feelings in sharing a treatment space among transgender individuals or differing sexual orientation.

Gender differences for privacy and in shared room preferences may result from the lasting impacts of prior sexual abuse or harassment. A history of sexual abuse negatively impacts later medical care access and use.15 Those veterans who experienced sexual abuse/harrassment reported higher feelings of lack of control, vulnerability, depression, and pursued less medical care.^15,16 Within cancer care, these feelings are most pronounced among women with gender-specific malignancies, such as gynecologic cancers or breast cancer. Treatment, screening, and physical examinations by clinicians who are of the same gender as the sexual abuse/harassment assailant can recreate traumatic feelings.^15,16

A majority of women (n = 18, 86%) in our cohort reported a history of sexual abuse or harassment and breast malignancy was the most common cancer among women. However women represent just 5.6% of the VAPHCS infusion unit treatment population. This combination of factors may explain the reasons for women veterans’ preference for privacy during treatments, access to gender-specific restrooms, and feeling more emotional support when surrounded by other women. Strategies to help patients with a history of abuse have been described and include discussions from the clinician asking about abuse history, allowing time for the patient to express fears with an examination or test, and training on how to deliver sensitive care for those with trauma.^17,18

Quality Improvement

Project In the VAPHCS infusion unit, several low-cost interventions have been undertaken as a result of our survey findings. We presented our survey data to the VAPHCS Cancer Committee, accredited through the national American College of Surgeons Commission on Cancer. The committee awarded support for a yearlong QI project, including a formal framework of quarterly multidisciplinary meetings to discuss project updates, challenges, and resources. The QI project centers on education to raise awareness of survey results as well as specific interventions for improvement.

Education efforts have been applied through multiple department-wide emails, in-person education to our chemotherapy unit staff, abstract submission to national oncology conferences, and grand rounds department presentations at VAPHCS and at other VHA-affiliated university programs. Additionally, education to clinicians with specific contact information for psychology and women’s health to support mental health, trauma, and sexual abuse histories has been given to each clinician who cares for veterans in the chemotherapy unit.

We also have implemented a mandatory cancer care navigation consultation for all women veterans who have a new cancer or infusion need. The cancer care navigator has received specialized training in sensitive history-taking and provides women veterans with a direct number to reach the cancer care navigation nurse. Cancer care navigation also provides a continuum of support and referral access for psychosocial needs as indicated between infusion or health care visits. Our hope is that these resources may help offset the sentiment reflected in our cohort of women feeling unable to voice concerns to a clinician.

Other interventions underway include offering designated scheduling time each week to women so they can receive infusions in an area with other women. This may help mitigate the finding that women veterans felt more uncomfortable around other patients during infusion treatments compared with how men felt in the chemotherapy unit. We also have implemented gender-specific restrooms labeled with a sign on each bathroom door so men and women can have access to a designated restroom. Offering private or semiprivate treatment rooms is currently limited by space and capacity; however, these may offer the greatest opportunity to improve patient satisfaction, especially among women veterans. Working with the support of the VAPHCS Cancer Committee, we aim to reevaluate the impact of the education and QI efforts on gender differences and patient satisfaction at completion of the 1-year award.

Limitations

Limitations to our study include the overall small sample size. This is due to the combination of the low number of women treated at VAPHCS and many with advanced cancer who, unfortunately, have a limited overall survival and hinders accrual of a larger sample size. Other limitations included age as a possible confounder in our findings, with women representing a younger demographic compared with men. We did not collect responses on duration of infusion time, which also may impact overall satisfaction and patient experience. We also acknowledge that biologic male or female sex may not correspond to a specific individual’s gender. Use of CPRS to obtain a matched number of male and female patients through random selection relied on labeled data from the EHR. This potentially may have excluded male patients who identify as another gender that would have been captured on the anonymous survey.

Conclusions

Our findings may have broad applications to other VHA facilities and other cancer-directed treatment centers where the patient demographic and open shared infusion unit design may be similar. The study also may serve as a model of survey design and implementation from which other centers may consider improving patient satisfaction. We hope these survey results and interventions can provide insight and be used to improve patient satisfaction among all cancer patients at infusion units serving veterans and nonveterans.

Acknowledgments

We are very thankful to our cancer patients who took the time to take the survey. We also are very grateful to the VHA infusion unit nurses, staff, nurse practitioners, and physicians who have embraced this project and welcomed any changes that may positively impact treatment of veterans. Also, thank you to Tia Kohs for statistical support and Sophie West for gender discussions. Last, we specifically thank Barbara, for her pursuit of better care for women and for all veterans.

Gender differences in patient satisfaction with medical care have been evaluated in multiple settings; however, studies specific to the unique population of women veterans with cancer are lacking. Women are reported to value privacy, psychosocial support, and communication to a higher degree compared with men.¹ Factors affecting satisfaction include the following: discomfort in sharing treatment rooms with the opposite gender, a desire for privacy with treatment and restroom use, anatomic or illness differences, and a personal history of abuse^.2-4 Regrettably, up to 1 in 3 women in the United States are victims of sexual trauma in their lifetimes, and up to 1 in 4 women in the military are victims of military sexual trauma. Incidence in both settings is suspected to be higher due to underreporting^.5,6

Chemotherapy treatment units are often uniquely designed as an open space, with several patients sharing a treatment area. The design reduces isolation and facilitates quick nurse-patient access during potentially toxic treatments known to have frequent adverse effects. Data suggest that nursing staff prefer open models to facilitate quick patient assessments and interventions as needed; however, patients and families prefer private treatment rooms, especially among women patients or those receiving longer infusions.⁷

The Veterans Health Administration (VHA) patient population is male predominant, comprised only of 10% female patients.8 Although the proportion of female patients in the VHA is expected to rise annually to about 16% by 2043, the low percentage of female veterans will persist for the foreseeable future.⁸ This low percentage of female veterans is reflected in the Veterans Affairs Portland Health Care System (VAPHCS) cancer patient population and in the use of the chemotherapy infusion unit, which is used for the ambulatory treatment of veterans undergoing cancer therapy.

The VHA has previously explored gender differences in health care, such as with cardiovascular disease, transgender care, and access to mental health.^9-11 However, to the best of our knowledge, no analysis has explored gender differences within the outpatient cancer treatment experience. Patient satisfaction with outpatient cancer care may be magnified in the VHA setting due to the uniquely unequal gender populations, shared treatment space design, and high incidence of sexual abuse among women veterans. Given this, we aimed to identify gender-related preferences in outpatient cancer care in our chemotherapy infusion unit.

In our study, we used the terms male and female to reflect statistical data from the literature or labeled data from the electronic health record (EHR); whereas the terms men and women were used to describe and encompass the cultural implications and context of gender.¹²

Methods

This study was designated as a quality improvement (QI) project by the VAPHCS research office and Institutional Review Board in accordance with VHA policies.

The VAPHCS outpatient chemotherapy infusion unit is designed with 6 rooms for chemotherapy administration. One room is a large open space with 6 chairs for patients. The other rooms are smaller with glass dividers between the rooms, and 3 chairs inside each for patients. There are 2 private bathrooms, each gender neutral. Direct patient care is provided by physicians, nurse practitioners (NPs), infusion unit nurses, and nurse coordinators. Men represent the majority of hematology and oncology physicians (13 of 20 total: 5 women fellow physicians and 2 women attending physicians), and 2 of 4 NPs. Women represent 10 of 12 infusion unit and cancer coordinator nurses. We used the VHA Computerized Patient Record System (CPRS) EHR, to create a list of veterans treated at the VAPHCS outpatient chemotherapy infusion unit for a 2-year period (January 1, 2018, to December 31, 2020).

Male and female patient lists were first generated based on CPRS categorization. We identified all female veterans treated in the ambulatory infusion unit during the study period. Male patients were then chosen at random, recording the most recent names for each year until a matched number per year compared with the female cohort was reached. Patients were recorded only once even though they had multiple infusion unit visits. Patients were excluded who were deceased, on hospice care, lost to follow-up, could not be reached by phone, refused to take the survey, had undeliverable email addresses, or lacked internet or email access.

After filing the appropriate request through the VAPHCS Institutional Review Board committee in January 2021, patient records were reviewed for demographics data, contact information, and infusion treatment history. The survey was then conducted over a 2-week period during January and February 2021. Each patient was invited by phone to complete a 25-question anonymous online survey. The survey questions were created from patient-relayed experiences, then modeled into survey questions in a format similar to other patient satisfaction questionnaires described in cancer care and gender differences.^2,13,14 The survey included self-identification of gender and was multiple choice for all except 2 questions, which allowed an open-ended response (Appendix). Only 1 answer per question was permitted. Only 1 survey link was sent to each veteran who gave permission for the survey. To protect anonymity for the small patient population, we excluded those identifying as gender nonbinary or transgender.

Statistical Analysis

Patient, disease, and treatment features are separated by male and female cohorts to reflect information from the EHR (Table 1). Survey percentages were calculated to reflect the affirmative response of the question asked (Table 2). Questions with answer options of not important, minimally important, important, or very important were calculated to reflect the sum of any importance in both cohorts. Questions with answer options of never, once, often, or every time were calculated to reflect any occurrence (sum of once, often, or every time) in both patient groups. Questions with answer options of strongly agree, somewhat agree, somewhat disagree, and strongly disagree were calculated to reflect any agreement (somewhat agree and strongly agree summed together) for both groups. Comparisons between cohorts were then conducted using a Fisher exact test. A Welch t test was used to calculate the significance of the continuous variable and overall ranking of the infusion unit experience between groups.

Results 

In 2020, 414 individual patients were treated at the VAPAHCS outpatient infusion unit. Of these, 23 (5.6%) were female, and 18 agreed to take the survey. After deceased and duplicate names from 2020 were removed, another 14 eligible 2019 female patients were invited and 6 agreed to participate; 6 eligible 2018 female patients were invited and 4 agreed to take the survey (Figure). Thirty female veterans were sent a survey link and 21 (70%) responses were collected. Twenty-one male 2020 patients were contacted and 18 agreed to take the survey. After removing duplicate names and deceased individuals, 17 of 21 eligible 2019 male patients and 4 of 6 eligible 2018 patients agreed to take the survey. Five additional male veterans declined the online-based survey method. In total, 39 male veterans were reached who agreed to have the survey link emailed, and 20 (51%) total responses were collected.

Most respondents answered all questions in the survey. The most frequently skipped questions included 3 questions that were contingent on a yes answer to a prior question, and 2 openended questions asking for a write-in response. Percentages for female and male respondents were adjusted for number of responses when applicable.

Thirteen (62%) female patients were aged < 65 years, while 18 (90%) of male patients were aged ≥ 65 years. Education beyond high school was reported in 20 female and 15 male respondents. Almost all treatment administered in the infusion unit was for cancer-directed treatment, with only 1 reporting a noncancer treatment (IV iron). The most common malignancy among female patients was breast cancer (n = 11, 52%); for male patients prostate cancer (n = 4, 20%) and hematologic malignancy (n = 4, 20%) were most common. Four (19%) female and 8 (40%) male respondents reported having a metastatic diagnosis. Overall patient satisfaction ranked high with an average score of 9.1 on a 10-point scale. The mean (SD) satisfaction score for female respondents was 1 point lower than that for men: 8.7 (2.2) vs 9.6 (0.6) in men (P = .11).

Eighteen (86%) women reported a history of sexual abuse or harassment compared with 2 (10%) men (P < .001). The sexual abuse assailant was a different gender for 17 of 18 female respondents and of the same gender for both male respondents. Of those with sexual abuse history, 4 women reported feeling uncomfortable around their assailant’s gender vs no men (P = .11), but this difference was not statistically significant. Six women (29%) and 2 (10%) men reported feeling uncomfortable during clinical examinations from comments made by the clinician or during treatment administration (P = .24). Six (29%) women and no men reported that they “felt uncomfortable in the infusion unit by other patients” (P = .02). Six (29%) women and no men reported feeling unable to “voice uncomfortable experiences” to the infusion unit clinician (P = .02).

Ten (48%) women and 6 (30%) men reported emotional support when receiving treatments provided by staff of the same gender (P = .34). Eight (38%) women and 4 (20%) men noted that access to treatment with the same gender was important (P = .31). Six (29%) women and 4 (20%) men indicated that access to a sex or gender-specific restroom was important (P = .72). No gender preferences were identified in the survey questions regarding importance of private treatment room access and level of emotional support when receiving treatment with others of the same malignancy. These relationships were not statistically significant.

In addition, 2 open-ended questions were asked. Seventeen women and 14 men responded. Contact the corresponding author for more information on the questions and responses.

Discussion

Overall patient satisfaction was high among the men and women veterans with cancer who received treatment in our outpatient infusion unit; however, notable gender differences existed. Three items in the survey revealed statistically significant differences in the patient experience between men and women veterans: history of sexual abuse or harassment, uncomfortable feelings among other patients, and discomfort in relaying uncomfortable feelings to a clinician. Other items in the survey did not reach statistical significance; however, we have included discussion of the findings as they may highlight important trends and be of clinical significance.

We suspect differences among genders in patient satisfaction to be related to the high incidence of sexual abuse or harassment history reported by women, much higher at 86% than the one-third to one-fourth incidence rates estimated by the existing literature for civilian or military sexual abuse in women.5,6 These high sexual abuse or harassment rates are present in a majority of women who receive cancer-directed treatment toward a gender-specific breast malignancy, surrounded predominantly among men in a shared treatment space. Together, these factors are likely key reasons behind the differences in satisfaction observed. This sentiment is expressed in our cohort, where one-fifth of women with a sexual abuse or harassment history continue to remain uncomfortable around men, and 29% of women reporting some uncomfortable feelings during their treatment experience compared with none of the men. Additionally, 6 (29%) women vs no men felt uncomfortable in reporting an uncomfortable experience with a clinician; this represents a significant barrier in providing care for these patients.

A key gender preference among women included access to shared treatment rooms with other women and that sharing a treatment space with other women resulted in feeling more emotional support during treatments. Access to gender-specific restrooms was also preferred by women more than men. Key findings in both genders were that about half of men and women valued access to a private treatment room and would derive more emotional support when surrounded by others with the same cancer.

Prior studies on gender and patient satisfaction in general medical care and cancer care have found women value privacy more than men.^1-3 Wessels and colleagues performed an analysis of 386 patients with cancer in Europe and found gender to be the strongest influence in patient preferences within cancer care. Specifically, the highest statically significant association in care preferences among women included privacy, support/counseling/rehabilitation access, and decreased wait times.2 These findings were most pronounced in those with breast cancer compared with other malignancy type and highlights that malignancy type and gender predominance impact care satisfaction.

Traditionally a shared treatment space design has been used in outpatient chemotherapy units, similar to the design of the VAPHCS. However, recent data report on the patient preference for a private treatment space, which was especially prominent among women and those receiving longer infusions.7 In another study that evaluated 225 patients with cancer preferences in sharing a treatment space with those of a different sexual orientation or gender identify, differences were found. Both men and women had a similar level of comfort in sharing a treatment room with someone of a different sexual orientation; however, more women reported discomfort in sharing a treatment space with a transgender woman compared with men who felt more comfortable sharing a space with a transgender man.4 We noted a gender preference may be present to explain the difference. Within our cohort, women valued access to treatment with other women and derived more emotional support when with other women; however, we did not inquire about feelings in sharing a treatment space among transgender individuals or differing sexual orientation.

Gender differences for privacy and in shared room preferences may result from the lasting impacts of prior sexual abuse or harassment. A history of sexual abuse negatively impacts later medical care access and use.15 Those veterans who experienced sexual abuse/harrassment reported higher feelings of lack of control, vulnerability, depression, and pursued less medical care.^15,16 Within cancer care, these feelings are most pronounced among women with gender-specific malignancies, such as gynecologic cancers or breast cancer. Treatment, screening, and physical examinations by clinicians who are of the same gender as the sexual abuse/harassment assailant can recreate traumatic feelings.^15,16

A majority of women (n = 18, 86%) in our cohort reported a history of sexual abuse or harassment and breast malignancy was the most common cancer among women. However women represent just 5.6% of the VAPHCS infusion unit treatment population. This combination of factors may explain the reasons for women veterans’ preference for privacy during treatments, access to gender-specific restrooms, and feeling more emotional support when surrounded by other women. Strategies to help patients with a history of abuse have been described and include discussions from the clinician asking about abuse history, allowing time for the patient to express fears with an examination or test, and training on how to deliver sensitive care for those with trauma.^17,18

Quality Improvement

Project In the VAPHCS infusion unit, several low-cost interventions have been undertaken as a result of our survey findings. We presented our survey data to the VAPHCS Cancer Committee, accredited through the national American College of Surgeons Commission on Cancer. The committee awarded support for a yearlong QI project, including a formal framework of quarterly multidisciplinary meetings to discuss project updates, challenges, and resources. The QI project centers on education to raise awareness of survey results as well as specific interventions for improvement.

Education efforts have been applied through multiple department-wide emails, in-person education to our chemotherapy unit staff, abstract submission to national oncology conferences, and grand rounds department presentations at VAPHCS and at other VHA-affiliated university programs. Additionally, education to clinicians with specific contact information for psychology and women’s health to support mental health, trauma, and sexual abuse histories has been given to each clinician who cares for veterans in the chemotherapy unit.

We also have implemented a mandatory cancer care navigation consultation for all women veterans who have a new cancer or infusion need. The cancer care navigator has received specialized training in sensitive history-taking and provides women veterans with a direct number to reach the cancer care navigation nurse. Cancer care navigation also provides a continuum of support and referral access for psychosocial needs as indicated between infusion or health care visits. Our hope is that these resources may help offset the sentiment reflected in our cohort of women feeling unable to voice concerns to a clinician.

Other interventions underway include offering designated scheduling time each week to women so they can receive infusions in an area with other women. This may help mitigate the finding that women veterans felt more uncomfortable around other patients during infusion treatments compared with how men felt in the chemotherapy unit. We also have implemented gender-specific restrooms labeled with a sign on each bathroom door so men and women can have access to a designated restroom. Offering private or semiprivate treatment rooms is currently limited by space and capacity; however, these may offer the greatest opportunity to improve patient satisfaction, especially among women veterans. Working with the support of the VAPHCS Cancer Committee, we aim to reevaluate the impact of the education and QI efforts on gender differences and patient satisfaction at completion of the 1-year award.

Limitations

Limitations to our study include the overall small sample size. This is due to the combination of the low number of women treated at VAPHCS and many with advanced cancer who, unfortunately, have a limited overall survival and hinders accrual of a larger sample size. Other limitations included age as a possible confounder in our findings, with women representing a younger demographic compared with men. We did not collect responses on duration of infusion time, which also may impact overall satisfaction and patient experience. We also acknowledge that biologic male or female sex may not correspond to a specific individual’s gender. Use of CPRS to obtain a matched number of male and female patients through random selection relied on labeled data from the EHR. This potentially may have excluded male patients who identify as another gender that would have been captured on the anonymous survey.

Conclusions

Our findings may have broad applications to other VHA facilities and other cancer-directed treatment centers where the patient demographic and open shared infusion unit design may be similar. The study also may serve as a model of survey design and implementation from which other centers may consider improving patient satisfaction. We hope these survey results and interventions can provide insight and be used to improve patient satisfaction among all cancer patients at infusion units serving veterans and nonveterans.

Acknowledgments

We are very thankful to our cancer patients who took the time to take the survey. We also are very grateful to the VHA infusion unit nurses, staff, nurse practitioners, and physicians who have embraced this project and welcomed any changes that may positively impact treatment of veterans. Also, thank you to Tia Kohs for statistical support and Sophie West for gender discussions. Last, we specifically thank Barbara, for her pursuit of better care for women and for all veterans.

Gender differences in patient satisfaction with medical care have been evaluated in multiple settings; however, studies specific to the unique population of women veterans with cancer are lacking. Women are reported to value privacy, psychosocial support, and communication to a higher degree compared with men.¹ Factors affecting satisfaction include the following: discomfort in sharing treatment rooms with the opposite gender, a desire for privacy with treatment and restroom use, anatomic or illness differences, and a personal history of abuse^.2-4 Regrettably, up to 1 in 3 women in the United States are victims of sexual trauma in their lifetimes, and up to 1 in 4 women in the military are victims of military sexual trauma. Incidence in both settings is suspected to be higher due to underreporting^.5,6

Chemotherapy treatment units are often uniquely designed as an open space, with several patients sharing a treatment area. The design reduces isolation and facilitates quick nurse-patient access during potentially toxic treatments known to have frequent adverse effects. Data suggest that nursing staff prefer open models to facilitate quick patient assessments and interventions as needed; however, patients and families prefer private treatment rooms, especially among women patients or those receiving longer infusions.⁷

The Veterans Health Administration (VHA) patient population is male predominant, comprised only of 10% female patients.8 Although the proportion of female patients in the VHA is expected to rise annually to about 16% by 2043, the low percentage of female veterans will persist for the foreseeable future.⁸ This low percentage of female veterans is reflected in the Veterans Affairs Portland Health Care System (VAPHCS) cancer patient population and in the use of the chemotherapy infusion unit, which is used for the ambulatory treatment of veterans undergoing cancer therapy.

The VHA has previously explored gender differences in health care, such as with cardiovascular disease, transgender care, and access to mental health.^9-11 However, to the best of our knowledge, no analysis has explored gender differences within the outpatient cancer treatment experience. Patient satisfaction with outpatient cancer care may be magnified in the VHA setting due to the uniquely unequal gender populations, shared treatment space design, and high incidence of sexual abuse among women veterans. Given this, we aimed to identify gender-related preferences in outpatient cancer care in our chemotherapy infusion unit.

In our study, we used the terms male and female to reflect statistical data from the literature or labeled data from the electronic health record (EHR); whereas the terms men and women were used to describe and encompass the cultural implications and context of gender.¹²

Methods

This study was designated as a quality improvement (QI) project by the VAPHCS research office and Institutional Review Board in accordance with VHA policies.

The VAPHCS outpatient chemotherapy infusion unit is designed with 6 rooms for chemotherapy administration. One room is a large open space with 6 chairs for patients. The other rooms are smaller with glass dividers between the rooms, and 3 chairs inside each for patients. There are 2 private bathrooms, each gender neutral. Direct patient care is provided by physicians, nurse practitioners (NPs), infusion unit nurses, and nurse coordinators. Men represent the majority of hematology and oncology physicians (13 of 20 total: 5 women fellow physicians and 2 women attending physicians), and 2 of 4 NPs. Women represent 10 of 12 infusion unit and cancer coordinator nurses. We used the VHA Computerized Patient Record System (CPRS) EHR, to create a list of veterans treated at the VAPHCS outpatient chemotherapy infusion unit for a 2-year period (January 1, 2018, to December 31, 2020).

Male and female patient lists were first generated based on CPRS categorization. We identified all female veterans treated in the ambulatory infusion unit during the study period. Male patients were then chosen at random, recording the most recent names for each year until a matched number per year compared with the female cohort was reached. Patients were recorded only once even though they had multiple infusion unit visits. Patients were excluded who were deceased, on hospice care, lost to follow-up, could not be reached by phone, refused to take the survey, had undeliverable email addresses, or lacked internet or email access.

After filing the appropriate request through the VAPHCS Institutional Review Board committee in January 2021, patient records were reviewed for demographics data, contact information, and infusion treatment history. The survey was then conducted over a 2-week period during January and February 2021. Each patient was invited by phone to complete a 25-question anonymous online survey. The survey questions were created from patient-relayed experiences, then modeled into survey questions in a format similar to other patient satisfaction questionnaires described in cancer care and gender differences.^2,13,14 The survey included self-identification of gender and was multiple choice for all except 2 questions, which allowed an open-ended response (Appendix). Only 1 answer per question was permitted. Only 1 survey link was sent to each veteran who gave permission for the survey. To protect anonymity for the small patient population, we excluded those identifying as gender nonbinary or transgender.

Statistical Analysis

Patient, disease, and treatment features are separated by male and female cohorts to reflect information from the EHR (Table 1). Survey percentages were calculated to reflect the affirmative response of the question asked (Table 2). Questions with answer options of not important, minimally important, important, or very important were calculated to reflect the sum of any importance in both cohorts. Questions with answer options of never, once, often, or every time were calculated to reflect any occurrence (sum of once, often, or every time) in both patient groups. Questions with answer options of strongly agree, somewhat agree, somewhat disagree, and strongly disagree were calculated to reflect any agreement (somewhat agree and strongly agree summed together) for both groups. Comparisons between cohorts were then conducted using a Fisher exact test. A Welch t test was used to calculate the significance of the continuous variable and overall ranking of the infusion unit experience between groups.

Results 

In 2020, 414 individual patients were treated at the VAPAHCS outpatient infusion unit. Of these, 23 (5.6%) were female, and 18 agreed to take the survey. After deceased and duplicate names from 2020 were removed, another 14 eligible 2019 female patients were invited and 6 agreed to participate; 6 eligible 2018 female patients were invited and 4 agreed to take the survey (Figure). Thirty female veterans were sent a survey link and 21 (70%) responses were collected. Twenty-one male 2020 patients were contacted and 18 agreed to take the survey. After removing duplicate names and deceased individuals, 17 of 21 eligible 2019 male patients and 4 of 6 eligible 2018 patients agreed to take the survey. Five additional male veterans declined the online-based survey method. In total, 39 male veterans were reached who agreed to have the survey link emailed, and 20 (51%) total responses were collected.

Most respondents answered all questions in the survey. The most frequently skipped questions included 3 questions that were contingent on a yes answer to a prior question, and 2 openended questions asking for a write-in response. Percentages for female and male respondents were adjusted for number of responses when applicable.

Thirteen (62%) female patients were aged < 65 years, while 18 (90%) of male patients were aged ≥ 65 years. Education beyond high school was reported in 20 female and 15 male respondents. Almost all treatment administered in the infusion unit was for cancer-directed treatment, with only 1 reporting a noncancer treatment (IV iron). The most common malignancy among female patients was breast cancer (n = 11, 52%); for male patients prostate cancer (n = 4, 20%) and hematologic malignancy (n = 4, 20%) were most common. Four (19%) female and 8 (40%) male respondents reported having a metastatic diagnosis. Overall patient satisfaction ranked high with an average score of 9.1 on a 10-point scale. The mean (SD) satisfaction score for female respondents was 1 point lower than that for men: 8.7 (2.2) vs 9.6 (0.6) in men (P = .11).

Eighteen (86%) women reported a history of sexual abuse or harassment compared with 2 (10%) men (P < .001). The sexual abuse assailant was a different gender for 17 of 18 female respondents and of the same gender for both male respondents. Of those with sexual abuse history, 4 women reported feeling uncomfortable around their assailant’s gender vs no men (P = .11), but this difference was not statistically significant. Six women (29%) and 2 (10%) men reported feeling uncomfortable during clinical examinations from comments made by the clinician or during treatment administration (P = .24). Six (29%) women and no men reported that they “felt uncomfortable in the infusion unit by other patients” (P = .02). Six (29%) women and no men reported feeling unable to “voice uncomfortable experiences” to the infusion unit clinician (P = .02).

Ten (48%) women and 6 (30%) men reported emotional support when receiving treatments provided by staff of the same gender (P = .34). Eight (38%) women and 4 (20%) men noted that access to treatment with the same gender was important (P = .31). Six (29%) women and 4 (20%) men indicated that access to a sex or gender-specific restroom was important (P = .72). No gender preferences were identified in the survey questions regarding importance of private treatment room access and level of emotional support when receiving treatment with others of the same malignancy. These relationships were not statistically significant.

In addition, 2 open-ended questions were asked. Seventeen women and 14 men responded. Contact the corresponding author for more information on the questions and responses.

Discussion

Overall patient satisfaction was high among the men and women veterans with cancer who received treatment in our outpatient infusion unit; however, notable gender differences existed. Three items in the survey revealed statistically significant differences in the patient experience between men and women veterans: history of sexual abuse or harassment, uncomfortable feelings among other patients, and discomfort in relaying uncomfortable feelings to a clinician. Other items in the survey did not reach statistical significance; however, we have included discussion of the findings as they may highlight important trends and be of clinical significance.

We suspect differences among genders in patient satisfaction to be related to the high incidence of sexual abuse or harassment history reported by women, much higher at 86% than the one-third to one-fourth incidence rates estimated by the existing literature for civilian or military sexual abuse in women.5,6 These high sexual abuse or harassment rates are present in a majority of women who receive cancer-directed treatment toward a gender-specific breast malignancy, surrounded predominantly among men in a shared treatment space. Together, these factors are likely key reasons behind the differences in satisfaction observed. This sentiment is expressed in our cohort, where one-fifth of women with a sexual abuse or harassment history continue to remain uncomfortable around men, and 29% of women reporting some uncomfortable feelings during their treatment experience compared with none of the men. Additionally, 6 (29%) women vs no men felt uncomfortable in reporting an uncomfortable experience with a clinician; this represents a significant barrier in providing care for these patients.

A key gender preference among women included access to shared treatment rooms with other women and that sharing a treatment space with other women resulted in feeling more emotional support during treatments. Access to gender-specific restrooms was also preferred by women more than men. Key findings in both genders were that about half of men and women valued access to a private treatment room and would derive more emotional support when surrounded by others with the same cancer.

Prior studies on gender and patient satisfaction in general medical care and cancer care have found women value privacy more than men.^1-3 Wessels and colleagues performed an analysis of 386 patients with cancer in Europe and found gender to be the strongest influence in patient preferences within cancer care. Specifically, the highest statically significant association in care preferences among women included privacy, support/counseling/rehabilitation access, and decreased wait times.2 These findings were most pronounced in those with breast cancer compared with other malignancy type and highlights that malignancy type and gender predominance impact care satisfaction.

Traditionally a shared treatment space design has been used in outpatient chemotherapy units, similar to the design of the VAPHCS. However, recent data report on the patient preference for a private treatment space, which was especially prominent among women and those receiving longer infusions.7 In another study that evaluated 225 patients with cancer preferences in sharing a treatment space with those of a different sexual orientation or gender identify, differences were found. Both men and women had a similar level of comfort in sharing a treatment room with someone of a different sexual orientation; however, more women reported discomfort in sharing a treatment space with a transgender woman compared with men who felt more comfortable sharing a space with a transgender man.4 We noted a gender preference may be present to explain the difference. Within our cohort, women valued access to treatment with other women and derived more emotional support when with other women; however, we did not inquire about feelings in sharing a treatment space among transgender individuals or differing sexual orientation.

Gender differences for privacy and in shared room preferences may result from the lasting impacts of prior sexual abuse or harassment. A history of sexual abuse negatively impacts later medical care access and use.15 Those veterans who experienced sexual abuse/harrassment reported higher feelings of lack of control, vulnerability, depression, and pursued less medical care.^15,16 Within cancer care, these feelings are most pronounced among women with gender-specific malignancies, such as gynecologic cancers or breast cancer. Treatment, screening, and physical examinations by clinicians who are of the same gender as the sexual abuse/harassment assailant can recreate traumatic feelings.^15,16

A majority of women (n = 18, 86%) in our cohort reported a history of sexual abuse or harassment and breast malignancy was the most common cancer among women. However women represent just 5.6% of the VAPHCS infusion unit treatment population. This combination of factors may explain the reasons for women veterans’ preference for privacy during treatments, access to gender-specific restrooms, and feeling more emotional support when surrounded by other women. Strategies to help patients with a history of abuse have been described and include discussions from the clinician asking about abuse history, allowing time for the patient to express fears with an examination or test, and training on how to deliver sensitive care for those with trauma.^17,18

Quality Improvement

Project In the VAPHCS infusion unit, several low-cost interventions have been undertaken as a result of our survey findings. We presented our survey data to the VAPHCS Cancer Committee, accredited through the national American College of Surgeons Commission on Cancer. The committee awarded support for a yearlong QI project, including a formal framework of quarterly multidisciplinary meetings to discuss project updates, challenges, and resources. The QI project centers on education to raise awareness of survey results as well as specific interventions for improvement.

Education efforts have been applied through multiple department-wide emails, in-person education to our chemotherapy unit staff, abstract submission to national oncology conferences, and grand rounds department presentations at VAPHCS and at other VHA-affiliated university programs. Additionally, education to clinicians with specific contact information for psychology and women’s health to support mental health, trauma, and sexual abuse histories has been given to each clinician who cares for veterans in the chemotherapy unit.

We also have implemented a mandatory cancer care navigation consultation for all women veterans who have a new cancer or infusion need. The cancer care navigator has received specialized training in sensitive history-taking and provides women veterans with a direct number to reach the cancer care navigation nurse. Cancer care navigation also provides a continuum of support and referral access for psychosocial needs as indicated between infusion or health care visits. Our hope is that these resources may help offset the sentiment reflected in our cohort of women feeling unable to voice concerns to a clinician.

Other interventions underway include offering designated scheduling time each week to women so they can receive infusions in an area with other women. This may help mitigate the finding that women veterans felt more uncomfortable around other patients during infusion treatments compared with how men felt in the chemotherapy unit. We also have implemented gender-specific restrooms labeled with a sign on each bathroom door so men and women can have access to a designated restroom. Offering private or semiprivate treatment rooms is currently limited by space and capacity; however, these may offer the greatest opportunity to improve patient satisfaction, especially among women veterans. Working with the support of the VAPHCS Cancer Committee, we aim to reevaluate the impact of the education and QI efforts on gender differences and patient satisfaction at completion of the 1-year award.

Limitations

Limitations to our study include the overall small sample size. This is due to the combination of the low number of women treated at VAPHCS and many with advanced cancer who, unfortunately, have a limited overall survival and hinders accrual of a larger sample size. Other limitations included age as a possible confounder in our findings, with women representing a younger demographic compared with men. We did not collect responses on duration of infusion time, which also may impact overall satisfaction and patient experience. We also acknowledge that biologic male or female sex may not correspond to a specific individual’s gender. Use of CPRS to obtain a matched number of male and female patients through random selection relied on labeled data from the EHR. This potentially may have excluded male patients who identify as another gender that would have been captured on the anonymous survey.

Conclusions

Our findings may have broad applications to other VHA facilities and other cancer-directed treatment centers where the patient demographic and open shared infusion unit design may be similar. The study also may serve as a model of survey design and implementation from which other centers may consider improving patient satisfaction. We hope these survey results and interventions can provide insight and be used to improve patient satisfaction among all cancer patients at infusion units serving veterans and nonveterans.

Acknowledgments

We are very thankful to our cancer patients who took the time to take the survey. We also are very grateful to the VHA infusion unit nurses, staff, nurse practitioners, and physicians who have embraced this project and welcomed any changes that may positively impact treatment of veterans. Also, thank you to Tia Kohs for statistical support and Sophie West for gender discussions. Last, we specifically thank Barbara, for her pursuit of better care for women and for all veterans.

People exposed to high levels of perfluorooctane sulfonic acid (PFOS) – a widely used synthetic chemical – run an increased risk of hepatocellular carcinoma, researchers say.

The correlation does not prove that PFOS causes this cancer, and more research is needed, but in the meantime, people should limit their exposure to it and others in its class, said Jesse Goodrich, PhD, a postdoctoral scholar in environmental medicine at the University of Southern California, Los Angeles.

“If you’re at risk for liver cancer because you have other risk factors, then these chemicals have the potential to kind of send you over the edge,” he told this news organization.

Dr. Goodrich and colleagues published their research online in JHEP Reports.

Dubbed “forever chemicals” because they can take thousands of years to break down, polyfluoroalkyl substances (PFAS) figure in makeup, food packaging, waterproof clothing, nonstick cookware, firefighting foams, and groundwater. They have spread through the atmosphere into rain and can be found in the blood of most Americans. PFOS is one of the most widely used PFAS.

“You can’t really escape them,” Dr. Goodrich said.

Previous research has linked PFAS to infertility, pregnancy complications, learning and behavioral problems in children, immune system issues, and higher cholesterol, as well as other cancers. Some experiments in animals suggested PFAS could cause liver cancer, and others showed a correlation between PFAS serum levels and biomarkers associated with liver cancer. But many of these health effects take a long time to develop.

“It wasn’t until we started to get really highly exposed groups of people that we started, as scientists, to be able to figure out what was going on,” said Dr. Goodrich.
 

High exposure, increased incidence

To measure the relationship between PFAS exposure and the incidence of hepatocellular carcinoma more definitively, Dr. Goodrich and colleagues analyzed data from the Multiethnic Cohort Study, a cohort of more than 200,000 people of African, Latin, Native Hawaiian, Japanese, and European ancestry tracked since the early 1990s in California and Hawaii. About 67,000 participants provided blood samples from 2001 to 2007.

From this cohort, the researchers found 50 people who later developed hepatocellular carcinoma. The researchers matched these patients with 50 controls of similar age at blood collection, sex, race, ethnicity, and study area who did not develop the cancer.

They found that people with more than 54.9 mcg/L of PFOS in their blood before any diagnosis of hepatocellular carcinoma were almost five times more likely to get the cancer (odds ratio 4.5; 95% confidence interval, 1.2-16.0), which was statistically significant (P = .02).

This level of PFOS corresponds to the 90th percentile found in the U.S. National Health and Nutrition Examination Survey (NHANES).

To get some idea of the mechanism by which PFOS might do its damage, the researchers also looked for linkage to levels of metabolites.

They found an overlap among high PFOS levels, hepatocellular carcinoma, and high levels of glucose, butyric acid (a short chain fatty acid), alpha-Ketoisovaleric acid (alpha branched-chain alpha-keto acid), and 7alpha-Hydroxy-3-oxo-4-cholestenoate (a bile acid). These metabolites have been associated in previous studies with metabolic disorders and liver disease.

Similarly, the researchers identified an association among the cancer, PFOS, and alterations in amino acid and glycan biosynthesis pathways.
 

Risk mitigation

The half-life of PFAS in the human body is about 3-7 years, said Dr. Goodrich.

“There’s not much you can do once they’re in there,” he said. “So, the focus needs to be on preventing the exposure in the first place.”

People can limit exposure by avoiding water contaminated with PFAS or filtering it out, Dr. Goodrich said. He recommended avoiding fish from contaminated waterways and nonstick cookware. The Environmental Protection Agency has more detailed recommendations.

But giving patients individualized recommendations is difficult, said Vincent Chen, MD, MS, a clinical instructor in gastroenterology at the University of Michigan, Ann Arbor, who was not involved in the study. Most clinicians don’t know their patients’ PFOS levels.

“It’s not that easy to get a test,” Dr. Chen told this news organization.

People can also mitigate their risk factors for hepatocellular carcinoma, such as a poor diet, a lack of exercise, and smoking, said Dr. Goodrich.

The researchers found that patients with hepatocellular carcinoma were more likely to be overweight and have diabetes, and PFOS was associated with higher fasting glucose levels. This raises the possibility that PFOS increases the risk for hepatocellular carcinoma by causing diabetes and obesity.

Dr. Goodrich and his colleagues tried to address this question by adjusting for baseline body mass index (BMI) and diabetes diagnosis in their statistical analysis.

After adjusting for BMI, they found that the association between PFOS and hepatocellular carcinoma diminished to a threefold risk (OR, 2.90; 95% CI, 0.78-10.00) and was no longer statistically significant (P = .11).

On the other hand, adjusting for diabetes did not change the significance of the relationship between PFOS and the cancer (OR, 5.7; 95% CI, 1.10-30.00; P = .04).

The sample size was probably too small to adequately tease out this relationship, Dr. Chen said. Still, he said, “I thought it was a very, very important study.”

The levels of PFOS found in the blood of Americans has been declining since the 1999-2000 NHANES, Dr. Chen pointed out. But that’s not as reassuring as it sounds.

“The problem is that if you put a regulation limiting the use of one PFAS, what people can do is just substitute with another PFAS or another molecule, which for all we know could be equally harmful,” Dr. Chen said.

Funding was provided by the Southern California Environmental Health Science Center supported by the National Institutes of Health. Dr. Goodrich and Dr. Chen report no relevant financial relationships.

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

People exposed to high levels of perfluorooctane sulfonic acid (PFOS) – a widely used synthetic chemical – run an increased risk of hepatocellular carcinoma, researchers say.

The correlation does not prove that PFOS causes this cancer, and more research is needed, but in the meantime, people should limit their exposure to it and others in its class, said Jesse Goodrich, PhD, a postdoctoral scholar in environmental medicine at the University of Southern California, Los Angeles.

“If you’re at risk for liver cancer because you have other risk factors, then these chemicals have the potential to kind of send you over the edge,” he told this news organization.

Dr. Goodrich and colleagues published their research online in JHEP Reports.

Dubbed “forever chemicals” because they can take thousands of years to break down, polyfluoroalkyl substances (PFAS) figure in makeup, food packaging, waterproof clothing, nonstick cookware, firefighting foams, and groundwater. They have spread through the atmosphere into rain and can be found in the blood of most Americans. PFOS is one of the most widely used PFAS.

“You can’t really escape them,” Dr. Goodrich said.

Previous research has linked PFAS to infertility, pregnancy complications, learning and behavioral problems in children, immune system issues, and higher cholesterol, as well as other cancers. Some experiments in animals suggested PFAS could cause liver cancer, and others showed a correlation between PFAS serum levels and biomarkers associated with liver cancer. But many of these health effects take a long time to develop.

“It wasn’t until we started to get really highly exposed groups of people that we started, as scientists, to be able to figure out what was going on,” said Dr. Goodrich.
 

High exposure, increased incidence

To measure the relationship between PFAS exposure and the incidence of hepatocellular carcinoma more definitively, Dr. Goodrich and colleagues analyzed data from the Multiethnic Cohort Study, a cohort of more than 200,000 people of African, Latin, Native Hawaiian, Japanese, and European ancestry tracked since the early 1990s in California and Hawaii. About 67,000 participants provided blood samples from 2001 to 2007.

From this cohort, the researchers found 50 people who later developed hepatocellular carcinoma. The researchers matched these patients with 50 controls of similar age at blood collection, sex, race, ethnicity, and study area who did not develop the cancer.

They found that people with more than 54.9 mcg/L of PFOS in their blood before any diagnosis of hepatocellular carcinoma were almost five times more likely to get the cancer (odds ratio 4.5; 95% confidence interval, 1.2-16.0), which was statistically significant (P = .02).

This level of PFOS corresponds to the 90th percentile found in the U.S. National Health and Nutrition Examination Survey (NHANES).

To get some idea of the mechanism by which PFOS might do its damage, the researchers also looked for linkage to levels of metabolites.

They found an overlap among high PFOS levels, hepatocellular carcinoma, and high levels of glucose, butyric acid (a short chain fatty acid), alpha-Ketoisovaleric acid (alpha branched-chain alpha-keto acid), and 7alpha-Hydroxy-3-oxo-4-cholestenoate (a bile acid). These metabolites have been associated in previous studies with metabolic disorders and liver disease.

Similarly, the researchers identified an association among the cancer, PFOS, and alterations in amino acid and glycan biosynthesis pathways.
 

Risk mitigation

The half-life of PFAS in the human body is about 3-7 years, said Dr. Goodrich.

“There’s not much you can do once they’re in there,” he said. “So, the focus needs to be on preventing the exposure in the first place.”

People can limit exposure by avoiding water contaminated with PFAS or filtering it out, Dr. Goodrich said. He recommended avoiding fish from contaminated waterways and nonstick cookware. The Environmental Protection Agency has more detailed recommendations.

But giving patients individualized recommendations is difficult, said Vincent Chen, MD, MS, a clinical instructor in gastroenterology at the University of Michigan, Ann Arbor, who was not involved in the study. Most clinicians don’t know their patients’ PFOS levels.

“It’s not that easy to get a test,” Dr. Chen told this news organization.

People can also mitigate their risk factors for hepatocellular carcinoma, such as a poor diet, a lack of exercise, and smoking, said Dr. Goodrich.

The researchers found that patients with hepatocellular carcinoma were more likely to be overweight and have diabetes, and PFOS was associated with higher fasting glucose levels. This raises the possibility that PFOS increases the risk for hepatocellular carcinoma by causing diabetes and obesity.

Dr. Goodrich and his colleagues tried to address this question by adjusting for baseline body mass index (BMI) and diabetes diagnosis in their statistical analysis.

After adjusting for BMI, they found that the association between PFOS and hepatocellular carcinoma diminished to a threefold risk (OR, 2.90; 95% CI, 0.78-10.00) and was no longer statistically significant (P = .11).

On the other hand, adjusting for diabetes did not change the significance of the relationship between PFOS and the cancer (OR, 5.7; 95% CI, 1.10-30.00; P = .04).

The sample size was probably too small to adequately tease out this relationship, Dr. Chen said. Still, he said, “I thought it was a very, very important study.”

The levels of PFOS found in the blood of Americans has been declining since the 1999-2000 NHANES, Dr. Chen pointed out. But that’s not as reassuring as it sounds.

“The problem is that if you put a regulation limiting the use of one PFAS, what people can do is just substitute with another PFAS or another molecule, which for all we know could be equally harmful,” Dr. Chen said.

Funding was provided by the Southern California Environmental Health Science Center supported by the National Institutes of Health. Dr. Goodrich and Dr. Chen report no relevant financial relationships.

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

People exposed to high levels of perfluorooctane sulfonic acid (PFOS) – a widely used synthetic chemical – run an increased risk of hepatocellular carcinoma, researchers say.

The correlation does not prove that PFOS causes this cancer, and more research is needed, but in the meantime, people should limit their exposure to it and others in its class, said Jesse Goodrich, PhD, a postdoctoral scholar in environmental medicine at the University of Southern California, Los Angeles.

“If you’re at risk for liver cancer because you have other risk factors, then these chemicals have the potential to kind of send you over the edge,” he told this news organization.

Dr. Goodrich and colleagues published their research online in JHEP Reports.

Dubbed “forever chemicals” because they can take thousands of years to break down, polyfluoroalkyl substances (PFAS) figure in makeup, food packaging, waterproof clothing, nonstick cookware, firefighting foams, and groundwater. They have spread through the atmosphere into rain and can be found in the blood of most Americans. PFOS is one of the most widely used PFAS.

“You can’t really escape them,” Dr. Goodrich said.

Previous research has linked PFAS to infertility, pregnancy complications, learning and behavioral problems in children, immune system issues, and higher cholesterol, as well as other cancers. Some experiments in animals suggested PFAS could cause liver cancer, and others showed a correlation between PFAS serum levels and biomarkers associated with liver cancer. But many of these health effects take a long time to develop.

“It wasn’t until we started to get really highly exposed groups of people that we started, as scientists, to be able to figure out what was going on,” said Dr. Goodrich.
 

High exposure, increased incidence

To measure the relationship between PFAS exposure and the incidence of hepatocellular carcinoma more definitively, Dr. Goodrich and colleagues analyzed data from the Multiethnic Cohort Study, a cohort of more than 200,000 people of African, Latin, Native Hawaiian, Japanese, and European ancestry tracked since the early 1990s in California and Hawaii. About 67,000 participants provided blood samples from 2001 to 2007.

From this cohort, the researchers found 50 people who later developed hepatocellular carcinoma. The researchers matched these patients with 50 controls of similar age at blood collection, sex, race, ethnicity, and study area who did not develop the cancer.

They found that people with more than 54.9 mcg/L of PFOS in their blood before any diagnosis of hepatocellular carcinoma were almost five times more likely to get the cancer (odds ratio 4.5; 95% confidence interval, 1.2-16.0), which was statistically significant (P = .02).

This level of PFOS corresponds to the 90th percentile found in the U.S. National Health and Nutrition Examination Survey (NHANES).

To get some idea of the mechanism by which PFOS might do its damage, the researchers also looked for linkage to levels of metabolites.

They found an overlap among high PFOS levels, hepatocellular carcinoma, and high levels of glucose, butyric acid (a short chain fatty acid), alpha-Ketoisovaleric acid (alpha branched-chain alpha-keto acid), and 7alpha-Hydroxy-3-oxo-4-cholestenoate (a bile acid). These metabolites have been associated in previous studies with metabolic disorders and liver disease.

Similarly, the researchers identified an association among the cancer, PFOS, and alterations in amino acid and glycan biosynthesis pathways.
 

Risk mitigation

The half-life of PFAS in the human body is about 3-7 years, said Dr. Goodrich.

“There’s not much you can do once they’re in there,” he said. “So, the focus needs to be on preventing the exposure in the first place.”

People can limit exposure by avoiding water contaminated with PFAS or filtering it out, Dr. Goodrich said. He recommended avoiding fish from contaminated waterways and nonstick cookware. The Environmental Protection Agency has more detailed recommendations.

But giving patients individualized recommendations is difficult, said Vincent Chen, MD, MS, a clinical instructor in gastroenterology at the University of Michigan, Ann Arbor, who was not involved in the study. Most clinicians don’t know their patients’ PFOS levels.

“It’s not that easy to get a test,” Dr. Chen told this news organization.

People can also mitigate their risk factors for hepatocellular carcinoma, such as a poor diet, a lack of exercise, and smoking, said Dr. Goodrich.

The researchers found that patients with hepatocellular carcinoma were more likely to be overweight and have diabetes, and PFOS was associated with higher fasting glucose levels. This raises the possibility that PFOS increases the risk for hepatocellular carcinoma by causing diabetes and obesity.

Dr. Goodrich and his colleagues tried to address this question by adjusting for baseline body mass index (BMI) and diabetes diagnosis in their statistical analysis.

After adjusting for BMI, they found that the association between PFOS and hepatocellular carcinoma diminished to a threefold risk (OR, 2.90; 95% CI, 0.78-10.00) and was no longer statistically significant (P = .11).

On the other hand, adjusting for diabetes did not change the significance of the relationship between PFOS and the cancer (OR, 5.7; 95% CI, 1.10-30.00; P = .04).

The sample size was probably too small to adequately tease out this relationship, Dr. Chen said. Still, he said, “I thought it was a very, very important study.”

The levels of PFOS found in the blood of Americans has been declining since the 1999-2000 NHANES, Dr. Chen pointed out. But that’s not as reassuring as it sounds.

“The problem is that if you put a regulation limiting the use of one PFAS, what people can do is just substitute with another PFAS or another molecule, which for all we know could be equally harmful,” Dr. Chen said.

Funding was provided by the Southern California Environmental Health Science Center supported by the National Institutes of Health. Dr. Goodrich and Dr. Chen report no relevant financial relationships.

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