Cancer

PHOENIX – A liquid biopsy test may accurately predict recurrence of human papillomavirus (HPV)–driven oropharyngeal squamous cell carcinoma (OPSCC) earlier than standard clinical and imaging assessments, a new analysis indicates.

Of 80 patients who tested positive for circulating tumor tissue–modified viral (TTMV)-HPV DNA during surveillance, 74% (n = 59) had no other evidence of disease or had indeterminate disease status.

And of those patients, 93% (n = 55) “later had proven recurrent, metastatic disease on imaging and/or biopsy,” according to Glenn Hanna, MD, from the Dana-Farber Cancer Institute, Boston, who presented the results Feb. 24 at the 2022 Multidisciplinary Head and Neck Cancers Symposium.

“This is the first study to demonstrate broad clinical utility and validity of the biomarker in HPV-driven oropharyngeal cancer,” Dr. Hanna said in a press release.

Although patients with HPV-driven OPSCC generally have favorable outcomes, up to 25% will experience recurrence after treatment.

Post-treatment surveillance currently relies on physical examinations and imaging, but Dr. Hanna and colleagues wanted to determine whether a routine circulating cell-free TTMV-HPV DNA test could detect occult recurrence sooner.

Dr. Hanna and colleagues analyzed the records of 1,076 patients with HPV-driven OPSCC at 118 sites in the U.S. who had completed therapy more than 3 months previously and undergone an TTMV-HPV DNA test (NavDx, Naveris) between June 2020 and November 2021.

The results of the test, which used ultrasensitive digital droplet PCR to identify HPV subtypes 16, 18, 31, 33, and 35, were compared with subsequent clinical evidence of OPSCC via nasopharyngolaryngoscopy, radiologic evaluations, or tissue biopsy.

Approximately 7% of the patients tested positive (n = 80) for circulating TTMV-HPV DNA. Of those, 26.2% (n = 21) had known clinical recurrence, while 73.8% (n = 59) had no other evidence of disease or an intermediate disease status.

Among those with no clinical evidence of recurrence, 93.2% (n = 55) had their recurrence subsequently confirmed using imaging or biopsy. Of the 4 remaining patients, 2 had clinically suspicious lesions, and 2 had no other evidence of disease.

Overall, the data indicate that the biomarker test demonstrated a 95% positive predictive value (76 of 80 patients) for recurrence or persistence of HPV-driven OPSCC.

According to Dr. Hanna, a positive TTMV-HPV DNA test was the first indicator of recurrence for 72% of patients, and almost half of recurrences were detected more than 12 months after completing therapy.

“Incorporating a test for TTMV-HPV DNA into routine post-treatment follow-up can enable physicians to detect recurrent cancers earlier and allow us to start recommended interventions more quickly to improve outcomes,” Dr. Hanna said in the release.

The study was supported by Naveris, which developed the TTMV-HPV DNA test studied. Dr. Hanna declares relationships with Actuate Therapeutics, Altor BioScience, Bicara, BMS, GSK, Merck, Regeneron, Sanofi/Genzyme, and others.

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

PHOENIX – A liquid biopsy test may accurately predict recurrence of human papillomavirus (HPV)–driven oropharyngeal squamous cell carcinoma (OPSCC) earlier than standard clinical and imaging assessments, a new analysis indicates.

Of 80 patients who tested positive for circulating tumor tissue–modified viral (TTMV)-HPV DNA during surveillance, 74% (n = 59) had no other evidence of disease or had indeterminate disease status.

And of those patients, 93% (n = 55) “later had proven recurrent, metastatic disease on imaging and/or biopsy,” according to Glenn Hanna, MD, from the Dana-Farber Cancer Institute, Boston, who presented the results Feb. 24 at the 2022 Multidisciplinary Head and Neck Cancers Symposium.

“This is the first study to demonstrate broad clinical utility and validity of the biomarker in HPV-driven oropharyngeal cancer,” Dr. Hanna said in a press release.

Although patients with HPV-driven OPSCC generally have favorable outcomes, up to 25% will experience recurrence after treatment.

Post-treatment surveillance currently relies on physical examinations and imaging, but Dr. Hanna and colleagues wanted to determine whether a routine circulating cell-free TTMV-HPV DNA test could detect occult recurrence sooner.

Dr. Hanna and colleagues analyzed the records of 1,076 patients with HPV-driven OPSCC at 118 sites in the U.S. who had completed therapy more than 3 months previously and undergone an TTMV-HPV DNA test (NavDx, Naveris) between June 2020 and November 2021.

The results of the test, which used ultrasensitive digital droplet PCR to identify HPV subtypes 16, 18, 31, 33, and 35, were compared with subsequent clinical evidence of OPSCC via nasopharyngolaryngoscopy, radiologic evaluations, or tissue biopsy.

Approximately 7% of the patients tested positive (n = 80) for circulating TTMV-HPV DNA. Of those, 26.2% (n = 21) had known clinical recurrence, while 73.8% (n = 59) had no other evidence of disease or an intermediate disease status.

Among those with no clinical evidence of recurrence, 93.2% (n = 55) had their recurrence subsequently confirmed using imaging or biopsy. Of the 4 remaining patients, 2 had clinically suspicious lesions, and 2 had no other evidence of disease.

Overall, the data indicate that the biomarker test demonstrated a 95% positive predictive value (76 of 80 patients) for recurrence or persistence of HPV-driven OPSCC.

According to Dr. Hanna, a positive TTMV-HPV DNA test was the first indicator of recurrence for 72% of patients, and almost half of recurrences were detected more than 12 months after completing therapy.

“Incorporating a test for TTMV-HPV DNA into routine post-treatment follow-up can enable physicians to detect recurrent cancers earlier and allow us to start recommended interventions more quickly to improve outcomes,” Dr. Hanna said in the release.

The study was supported by Naveris, which developed the TTMV-HPV DNA test studied. Dr. Hanna declares relationships with Actuate Therapeutics, Altor BioScience, Bicara, BMS, GSK, Merck, Regeneron, Sanofi/Genzyme, and others.

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

PHOENIX – A liquid biopsy test may accurately predict recurrence of human papillomavirus (HPV)–driven oropharyngeal squamous cell carcinoma (OPSCC) earlier than standard clinical and imaging assessments, a new analysis indicates.

Of 80 patients who tested positive for circulating tumor tissue–modified viral (TTMV)-HPV DNA during surveillance, 74% (n = 59) had no other evidence of disease or had indeterminate disease status.

And of those patients, 93% (n = 55) “later had proven recurrent, metastatic disease on imaging and/or biopsy,” according to Glenn Hanna, MD, from the Dana-Farber Cancer Institute, Boston, who presented the results Feb. 24 at the 2022 Multidisciplinary Head and Neck Cancers Symposium.

“This is the first study to demonstrate broad clinical utility and validity of the biomarker in HPV-driven oropharyngeal cancer,” Dr. Hanna said in a press release.

Although patients with HPV-driven OPSCC generally have favorable outcomes, up to 25% will experience recurrence after treatment.

Post-treatment surveillance currently relies on physical examinations and imaging, but Dr. Hanna and colleagues wanted to determine whether a routine circulating cell-free TTMV-HPV DNA test could detect occult recurrence sooner.

Dr. Hanna and colleagues analyzed the records of 1,076 patients with HPV-driven OPSCC at 118 sites in the U.S. who had completed therapy more than 3 months previously and undergone an TTMV-HPV DNA test (NavDx, Naveris) between June 2020 and November 2021.

The results of the test, which used ultrasensitive digital droplet PCR to identify HPV subtypes 16, 18, 31, 33, and 35, were compared with subsequent clinical evidence of OPSCC via nasopharyngolaryngoscopy, radiologic evaluations, or tissue biopsy.

Approximately 7% of the patients tested positive (n = 80) for circulating TTMV-HPV DNA. Of those, 26.2% (n = 21) had known clinical recurrence, while 73.8% (n = 59) had no other evidence of disease or an intermediate disease status.

Among those with no clinical evidence of recurrence, 93.2% (n = 55) had their recurrence subsequently confirmed using imaging or biopsy. Of the 4 remaining patients, 2 had clinically suspicious lesions, and 2 had no other evidence of disease.

Overall, the data indicate that the biomarker test demonstrated a 95% positive predictive value (76 of 80 patients) for recurrence or persistence of HPV-driven OPSCC.

According to Dr. Hanna, a positive TTMV-HPV DNA test was the first indicator of recurrence for 72% of patients, and almost half of recurrences were detected more than 12 months after completing therapy.

“Incorporating a test for TTMV-HPV DNA into routine post-treatment follow-up can enable physicians to detect recurrent cancers earlier and allow us to start recommended interventions more quickly to improve outcomes,” Dr. Hanna said in the release.

The study was supported by Naveris, which developed the TTMV-HPV DNA test studied. Dr. Hanna declares relationships with Actuate Therapeutics, Altor BioScience, Bicara, BMS, GSK, Merck, Regeneron, Sanofi/Genzyme, and others.

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

Incidence rates for testicular cancer have been rising in the United States, as have related mortality rates, but there are wide variations by race/ethnicity and geographic location, a new analysis shows.

Testicular cancer is the most common type of malignancy in young men between the ages of 20 and 34 years, although overall, it is relatively uncommon and represents only 0.5% of all new cancer cases in the U.S.

The new analysis shows that age-adjusted testicular cancer–specific mortality rates in the United States increased from 1999-2019, particularly among Hispanic men. During the same period, mortality rates declined somewhat among Black men as compared to White men.

“Given that testicular cancer generally has a favorable prognosis, it is concerning that mortality rates for this disease are increasing,” said lead author Anushka Ghosh, BS, a clinical research coordinator at Massachusetts General Hospital, Boston. “It is crucial to understand these trends and make targeted efforts to address any geographic, racial, and ethnic gaps in testicular cancer care.”

She presented the findings at the Genitourinary Cancers Symposium (GUCS) 2022.

“Testicular cancer is a rare but very curable disease,” said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment. “The increase in testicular cancer deaths for Hispanic men is concerning.”

“Whether this change relates to suboptimal access to appropriate care or change in biology as a result of socioeconomic or geographic changes in Hispanic men over the recent years is unknown but needs to be urgently explored and addressed,” he added.
 

Details of the new findings

For their analysis, Ms. Ghosh and colleagues assessed recent changes in testicular cancer mortality rates over time in the United States with respect to race, ethnicity, and geography. They used the Centers for Disease Control’s Wide-Ranging Online Data for Epidemiologic Research database to obtain the number of age-adjusted death rates for individuals across all U.S. counties over a 21-year period (1999-2019).

During this period, overall age-adjusted testicular cancer mortality rates rose slowly but not significantly, with an overall increase of 0.0002 per 100,000 population per year. This increase was significantly worse among Hispanic men, among whom the increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

But when stratified by race (Black vs. White), the authors saw that Black men had somewhat improved rates. Among Black men, the rate decreased by 0.0007 per 100,000, compared with an increase of 0.0006 per 100,000 among White men, a difference that reached statistical significance (P = .049).

“We also observed significant geographical differences in mortality rates,” said Ms. Ghosh.

They divided the U.S. into four regions: the Northeast, the Midwest, the South, and the West. There were no differences in the South and the Midwest, but mortality rates decreased in the Northeast by 0.00092 per 100,000 and rose in the West by 0.00086 per 100,000 (P for difference between slopes = .032).

The authors also looked at differences in urbanization categories or population density and found that large central metro regions (central counties in metro areas with population greater than 1 million) and small metro regions (counties with population 50,000-249,999) were significantly different. While testicular cancer mortality rates decreased slightly in large central metropolitan regions by 0.0004, rates increased slightly in small metropolitan regions (0.0022; P for difference = .048). No other significant differences based on urbanization were noted.

Also approached for comment, Matt D. Galsky, MD, director of genitourinary medical oncology at the Tisch Cancer Institute at Mount Sinai, noted that the finding that testicular cancer mortality rates increased from 1999-2019 was not statistically significant.

However, there were significant trends among subgroups. Testicular cancer mortality increased during this period among Hispanic men, he pointed out. “Importantly, while statistically significant, the differences are numerically small. That said, testicular cancer is a generally a highly curable malignancy, so any disparities related to mortality may be notable and worth further investigation.

“There are several potential underlying causes of such disparities, some of which could be probed with additional clinical details, and some of which might involve a more complex interplay of access and tumor biology,” he continued. “For example, testicular cancers are broadly separated into two subtypes: seminoma and nonseminoma. Whether the trends in these two subtypes in Hispanic men are different compared to non-Hispanic men could be one clue into the observed disparities.”

Ms. Ghosh, Dr. Geynisman, and Dr. Galsky have disclosed no relevant financial relationships.

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

Incidence rates for testicular cancer have been rising in the United States, as have related mortality rates, but there are wide variations by race/ethnicity and geographic location, a new analysis shows.

Testicular cancer is the most common type of malignancy in young men between the ages of 20 and 34 years, although overall, it is relatively uncommon and represents only 0.5% of all new cancer cases in the U.S.

The new analysis shows that age-adjusted testicular cancer–specific mortality rates in the United States increased from 1999-2019, particularly among Hispanic men. During the same period, mortality rates declined somewhat among Black men as compared to White men.

“Given that testicular cancer generally has a favorable prognosis, it is concerning that mortality rates for this disease are increasing,” said lead author Anushka Ghosh, BS, a clinical research coordinator at Massachusetts General Hospital, Boston. “It is crucial to understand these trends and make targeted efforts to address any geographic, racial, and ethnic gaps in testicular cancer care.”

She presented the findings at the Genitourinary Cancers Symposium (GUCS) 2022.

“Testicular cancer is a rare but very curable disease,” said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment. “The increase in testicular cancer deaths for Hispanic men is concerning.”

“Whether this change relates to suboptimal access to appropriate care or change in biology as a result of socioeconomic or geographic changes in Hispanic men over the recent years is unknown but needs to be urgently explored and addressed,” he added.
 

Details of the new findings

For their analysis, Ms. Ghosh and colleagues assessed recent changes in testicular cancer mortality rates over time in the United States with respect to race, ethnicity, and geography. They used the Centers for Disease Control’s Wide-Ranging Online Data for Epidemiologic Research database to obtain the number of age-adjusted death rates for individuals across all U.S. counties over a 21-year period (1999-2019).

During this period, overall age-adjusted testicular cancer mortality rates rose slowly but not significantly, with an overall increase of 0.0002 per 100,000 population per year. This increase was significantly worse among Hispanic men, among whom the increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

But when stratified by race (Black vs. White), the authors saw that Black men had somewhat improved rates. Among Black men, the rate decreased by 0.0007 per 100,000, compared with an increase of 0.0006 per 100,000 among White men, a difference that reached statistical significance (P = .049).

“We also observed significant geographical differences in mortality rates,” said Ms. Ghosh.

They divided the U.S. into four regions: the Northeast, the Midwest, the South, and the West. There were no differences in the South and the Midwest, but mortality rates decreased in the Northeast by 0.00092 per 100,000 and rose in the West by 0.00086 per 100,000 (P for difference between slopes = .032).

The authors also looked at differences in urbanization categories or population density and found that large central metro regions (central counties in metro areas with population greater than 1 million) and small metro regions (counties with population 50,000-249,999) were significantly different. While testicular cancer mortality rates decreased slightly in large central metropolitan regions by 0.0004, rates increased slightly in small metropolitan regions (0.0022; P for difference = .048). No other significant differences based on urbanization were noted.

Also approached for comment, Matt D. Galsky, MD, director of genitourinary medical oncology at the Tisch Cancer Institute at Mount Sinai, noted that the finding that testicular cancer mortality rates increased from 1999-2019 was not statistically significant.

However, there were significant trends among subgroups. Testicular cancer mortality increased during this period among Hispanic men, he pointed out. “Importantly, while statistically significant, the differences are numerically small. That said, testicular cancer is a generally a highly curable malignancy, so any disparities related to mortality may be notable and worth further investigation.

“There are several potential underlying causes of such disparities, some of which could be probed with additional clinical details, and some of which might involve a more complex interplay of access and tumor biology,” he continued. “For example, testicular cancers are broadly separated into two subtypes: seminoma and nonseminoma. Whether the trends in these two subtypes in Hispanic men are different compared to non-Hispanic men could be one clue into the observed disparities.”

Ms. Ghosh, Dr. Geynisman, and Dr. Galsky have disclosed no relevant financial relationships.

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

Incidence rates for testicular cancer have been rising in the United States, as have related mortality rates, but there are wide variations by race/ethnicity and geographic location, a new analysis shows.

Testicular cancer is the most common type of malignancy in young men between the ages of 20 and 34 years, although overall, it is relatively uncommon and represents only 0.5% of all new cancer cases in the U.S.

The new analysis shows that age-adjusted testicular cancer–specific mortality rates in the United States increased from 1999-2019, particularly among Hispanic men. During the same period, mortality rates declined somewhat among Black men as compared to White men.

“Given that testicular cancer generally has a favorable prognosis, it is concerning that mortality rates for this disease are increasing,” said lead author Anushka Ghosh, BS, a clinical research coordinator at Massachusetts General Hospital, Boston. “It is crucial to understand these trends and make targeted efforts to address any geographic, racial, and ethnic gaps in testicular cancer care.”

She presented the findings at the Genitourinary Cancers Symposium (GUCS) 2022.

“Testicular cancer is a rare but very curable disease,” said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment. “The increase in testicular cancer deaths for Hispanic men is concerning.”

“Whether this change relates to suboptimal access to appropriate care or change in biology as a result of socioeconomic or geographic changes in Hispanic men over the recent years is unknown but needs to be urgently explored and addressed,” he added.
 

Details of the new findings

For their analysis, Ms. Ghosh and colleagues assessed recent changes in testicular cancer mortality rates over time in the United States with respect to race, ethnicity, and geography. They used the Centers for Disease Control’s Wide-Ranging Online Data for Epidemiologic Research database to obtain the number of age-adjusted death rates for individuals across all U.S. counties over a 21-year period (1999-2019).

During this period, overall age-adjusted testicular cancer mortality rates rose slowly but not significantly, with an overall increase of 0.0002 per 100,000 population per year. This increase was significantly worse among Hispanic men, among whom the increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

But when stratified by race (Black vs. White), the authors saw that Black men had somewhat improved rates. Among Black men, the rate decreased by 0.0007 per 100,000, compared with an increase of 0.0006 per 100,000 among White men, a difference that reached statistical significance (P = .049).

“We also observed significant geographical differences in mortality rates,” said Ms. Ghosh.

They divided the U.S. into four regions: the Northeast, the Midwest, the South, and the West. There were no differences in the South and the Midwest, but mortality rates decreased in the Northeast by 0.00092 per 100,000 and rose in the West by 0.00086 per 100,000 (P for difference between slopes = .032).

The authors also looked at differences in urbanization categories or population density and found that large central metro regions (central counties in metro areas with population greater than 1 million) and small metro regions (counties with population 50,000-249,999) were significantly different. While testicular cancer mortality rates decreased slightly in large central metropolitan regions by 0.0004, rates increased slightly in small metropolitan regions (0.0022; P for difference = .048). No other significant differences based on urbanization were noted.

Also approached for comment, Matt D. Galsky, MD, director of genitourinary medical oncology at the Tisch Cancer Institute at Mount Sinai, noted that the finding that testicular cancer mortality rates increased from 1999-2019 was not statistically significant.

However, there were significant trends among subgroups. Testicular cancer mortality increased during this period among Hispanic men, he pointed out. “Importantly, while statistically significant, the differences are numerically small. That said, testicular cancer is a generally a highly curable malignancy, so any disparities related to mortality may be notable and worth further investigation.

“There are several potential underlying causes of such disparities, some of which could be probed with additional clinical details, and some of which might involve a more complex interplay of access and tumor biology,” he continued. “For example, testicular cancers are broadly separated into two subtypes: seminoma and nonseminoma. Whether the trends in these two subtypes in Hispanic men are different compared to non-Hispanic men could be one clue into the observed disparities.”

Ms. Ghosh, Dr. Geynisman, and Dr. Galsky have disclosed no relevant financial relationships.

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

The U.S. Preventive Services Task Force (USPSTF) criteria for lung cancer screening should be expanded to include more women, especially those with a history of breast cancer, according to a new study published in BJS Open.

The 2021 screening guidelines include adults aged between 50 and 80 years who have a 20–pack-year smoking history and currently smoke or have quit within the past 15 years, but the guidelines do not include nonsmokers or patients with a history of previous malignancies, such as breast cancer.

Led by Daniela Molena, MD, a thoracic surgeon and director of esophageal surgery at Memorial Sloan Kettering Cancer Center, New York, researchers conducted an analysis of 2,192 women with first-time lung cancer who underwent lung resections at Memorial Sloan Kettering between January 2000 and December 2017. The study’s objective was to determine stage at diagnosis, survival, and eligibility for lung cancer screening among patients with lung cancer who had a previous breast cancer diagnosis and those who did not have a history of breast cancer.

Only 331 (15.1%) patients were previously diagnosed with breast cancer, which was not statistically significant. “Overall, there were no statistically significant differences in genomic or oncogenic pathway alterations between the two groups, which suggests that lung cancer in patients who previously had breast cancer may not be affected at the genomic level by the previous breast cancer,” the authors wrote.

However, at 58.4%, more than half of patients in the study (1,281 patients) were prior smokers and only 33.3% met the USPSTF criteria for lung cancer screening, which the authors said was concerning.

“The most important finding of the study was that a high percentage of women with lung cancer, regardless of breast cancer history, did not meet the current USPSTF criteria for lung cancer screening. This is very important given the observation that nearly half of the women included in the study did not have a history of smoking. As such, the role of imaging for other causes, such as cancer surveillance, becomes especially important for early cancer diagnosis,” Dr. Molena and colleagues wrote. “To reduce late-stage cancer diagnoses, further assessment of guidelines for lung cancer screening for all women may be needed.”

Instead, for almost half of women in the study group with a history of breast cancer, the lung cancer was detected on a routine follow-up imaging scan.

USPSTF guidelines for lung cancer screening do not include previous malignancy as a high-risk feature requiring evaluation, which may explain why so few women in this study were screened for lung cancer, even though lung cancer is more common in breast cancer survivors than the general population. Approximately 10% of women who have had breast cancer will develop a second malignancy within 10 years and in most cases, it will be lung cancer. Plus, according to the National Cancer Institute, breast, lung, and colorectal cancers are the three most common cancers in women and account for approximately 50% of all new cancer diagnoses in women in 2020.

A 2018 analysis published in Frontiers in Oncology found that, of more than 6,000 women with secondary primary lung cancer after having had breast cancer, 42% had distant-stage disease at the time of diagnosis which, Dr. Molena and colleagues said, suggests an ongoing need to update screening recommendations.

“Given that lung cancer has a 5-year overall survival rate of less than 20% (highlighting the benefits of early-stage diagnosis), a better understanding of lung cancer in women with a history of breast cancer could have important implications for screening and surveillance,” the authors wrote.

Estrogen is known to play a role in the development of lung cancer by activating the epidermal growth factor receptor (EGFR). Previous research has shown an increased risk of lung cancer in patients with estrogen receptor–negative, progesterone receptor–negative, HER2-negative, or triple-negative breast cancer.

“Antiestrogen treatment has been demonstrated to decrease the incidence of lung cancer and has been associated with improved long-term survival in patients with lung cancer after breast cancer. Future studies should seek to identify high-risk populations on the basis of hormone receptor status and antiestrogen therapy use,” the authors wrote.

The authors noted a number of limitations to the study, including the single hospital as the sole source of data, plus, the analysis did not account for the length of time since patients quit smoking and a lung cancer diagnosis. Nor did it consider other risk factors, such as radiation, chemotherapy, or antiestrogen therapies.

The authors did not disclose any study-related conflicts of interests.

This article was updated 3/2/22.

The U.S. Preventive Services Task Force (USPSTF) criteria for lung cancer screening should be expanded to include more women, especially those with a history of breast cancer, according to a new study published in BJS Open.

The 2021 screening guidelines include adults aged between 50 and 80 years who have a 20–pack-year smoking history and currently smoke or have quit within the past 15 years, but the guidelines do not include nonsmokers or patients with a history of previous malignancies, such as breast cancer.

Led by Daniela Molena, MD, a thoracic surgeon and director of esophageal surgery at Memorial Sloan Kettering Cancer Center, New York, researchers conducted an analysis of 2,192 women with first-time lung cancer who underwent lung resections at Memorial Sloan Kettering between January 2000 and December 2017. The study’s objective was to determine stage at diagnosis, survival, and eligibility for lung cancer screening among patients with lung cancer who had a previous breast cancer diagnosis and those who did not have a history of breast cancer.

Only 331 (15.1%) patients were previously diagnosed with breast cancer, which was not statistically significant. “Overall, there were no statistically significant differences in genomic or oncogenic pathway alterations between the two groups, which suggests that lung cancer in patients who previously had breast cancer may not be affected at the genomic level by the previous breast cancer,” the authors wrote.

However, at 58.4%, more than half of patients in the study (1,281 patients) were prior smokers and only 33.3% met the USPSTF criteria for lung cancer screening, which the authors said was concerning.

“The most important finding of the study was that a high percentage of women with lung cancer, regardless of breast cancer history, did not meet the current USPSTF criteria for lung cancer screening. This is very important given the observation that nearly half of the women included in the study did not have a history of smoking. As such, the role of imaging for other causes, such as cancer surveillance, becomes especially important for early cancer diagnosis,” Dr. Molena and colleagues wrote. “To reduce late-stage cancer diagnoses, further assessment of guidelines for lung cancer screening for all women may be needed.”

Instead, for almost half of women in the study group with a history of breast cancer, the lung cancer was detected on a routine follow-up imaging scan.

USPSTF guidelines for lung cancer screening do not include previous malignancy as a high-risk feature requiring evaluation, which may explain why so few women in this study were screened for lung cancer, even though lung cancer is more common in breast cancer survivors than the general population. Approximately 10% of women who have had breast cancer will develop a second malignancy within 10 years and in most cases, it will be lung cancer. Plus, according to the National Cancer Institute, breast, lung, and colorectal cancers are the three most common cancers in women and account for approximately 50% of all new cancer diagnoses in women in 2020.

A 2018 analysis published in Frontiers in Oncology found that, of more than 6,000 women with secondary primary lung cancer after having had breast cancer, 42% had distant-stage disease at the time of diagnosis which, Dr. Molena and colleagues said, suggests an ongoing need to update screening recommendations.

“Given that lung cancer has a 5-year overall survival rate of less than 20% (highlighting the benefits of early-stage diagnosis), a better understanding of lung cancer in women with a history of breast cancer could have important implications for screening and surveillance,” the authors wrote.

Estrogen is known to play a role in the development of lung cancer by activating the epidermal growth factor receptor (EGFR). Previous research has shown an increased risk of lung cancer in patients with estrogen receptor–negative, progesterone receptor–negative, HER2-negative, or triple-negative breast cancer.

“Antiestrogen treatment has been demonstrated to decrease the incidence of lung cancer and has been associated with improved long-term survival in patients with lung cancer after breast cancer. Future studies should seek to identify high-risk populations on the basis of hormone receptor status and antiestrogen therapy use,” the authors wrote.

The authors noted a number of limitations to the study, including the single hospital as the sole source of data, plus, the analysis did not account for the length of time since patients quit smoking and a lung cancer diagnosis. Nor did it consider other risk factors, such as radiation, chemotherapy, or antiestrogen therapies.

The authors did not disclose any study-related conflicts of interests.

This article was updated 3/2/22.

The U.S. Preventive Services Task Force (USPSTF) criteria for lung cancer screening should be expanded to include more women, especially those with a history of breast cancer, according to a new study published in BJS Open.

The 2021 screening guidelines include adults aged between 50 and 80 years who have a 20–pack-year smoking history and currently smoke or have quit within the past 15 years, but the guidelines do not include nonsmokers or patients with a history of previous malignancies, such as breast cancer.

Led by Daniela Molena, MD, a thoracic surgeon and director of esophageal surgery at Memorial Sloan Kettering Cancer Center, New York, researchers conducted an analysis of 2,192 women with first-time lung cancer who underwent lung resections at Memorial Sloan Kettering between January 2000 and December 2017. The study’s objective was to determine stage at diagnosis, survival, and eligibility for lung cancer screening among patients with lung cancer who had a previous breast cancer diagnosis and those who did not have a history of breast cancer.

Only 331 (15.1%) patients were previously diagnosed with breast cancer, which was not statistically significant. “Overall, there were no statistically significant differences in genomic or oncogenic pathway alterations between the two groups, which suggests that lung cancer in patients who previously had breast cancer may not be affected at the genomic level by the previous breast cancer,” the authors wrote.

However, at 58.4%, more than half of patients in the study (1,281 patients) were prior smokers and only 33.3% met the USPSTF criteria for lung cancer screening, which the authors said was concerning.

“The most important finding of the study was that a high percentage of women with lung cancer, regardless of breast cancer history, did not meet the current USPSTF criteria for lung cancer screening. This is very important given the observation that nearly half of the women included in the study did not have a history of smoking. As such, the role of imaging for other causes, such as cancer surveillance, becomes especially important for early cancer diagnosis,” Dr. Molena and colleagues wrote. “To reduce late-stage cancer diagnoses, further assessment of guidelines for lung cancer screening for all women may be needed.”

Instead, for almost half of women in the study group with a history of breast cancer, the lung cancer was detected on a routine follow-up imaging scan.

USPSTF guidelines for lung cancer screening do not include previous malignancy as a high-risk feature requiring evaluation, which may explain why so few women in this study were screened for lung cancer, even though lung cancer is more common in breast cancer survivors than the general population. Approximately 10% of women who have had breast cancer will develop a second malignancy within 10 years and in most cases, it will be lung cancer. Plus, according to the National Cancer Institute, breast, lung, and colorectal cancers are the three most common cancers in women and account for approximately 50% of all new cancer diagnoses in women in 2020.

A 2018 analysis published in Frontiers in Oncology found that, of more than 6,000 women with secondary primary lung cancer after having had breast cancer, 42% had distant-stage disease at the time of diagnosis which, Dr. Molena and colleagues said, suggests an ongoing need to update screening recommendations.

“Given that lung cancer has a 5-year overall survival rate of less than 20% (highlighting the benefits of early-stage diagnosis), a better understanding of lung cancer in women with a history of breast cancer could have important implications for screening and surveillance,” the authors wrote.

Estrogen is known to play a role in the development of lung cancer by activating the epidermal growth factor receptor (EGFR). Previous research has shown an increased risk of lung cancer in patients with estrogen receptor–negative, progesterone receptor–negative, HER2-negative, or triple-negative breast cancer.

“Antiestrogen treatment has been demonstrated to decrease the incidence of lung cancer and has been associated with improved long-term survival in patients with lung cancer after breast cancer. Future studies should seek to identify high-risk populations on the basis of hormone receptor status and antiestrogen therapy use,” the authors wrote.

The authors noted a number of limitations to the study, including the single hospital as the sole source of data, plus, the analysis did not account for the length of time since patients quit smoking and a lung cancer diagnosis. Nor did it consider other risk factors, such as radiation, chemotherapy, or antiestrogen therapies.

The authors did not disclose any study-related conflicts of interests.

This article was updated 3/2/22.

A new treatment option for patients with refractory/relapsed multiple myeloma who have already tried four or more therapies has been approved by the U.S. Food and Drug Administration.

The product, ciltacabtagene autoleucel (cilta-cel), will be marketed as Carvykti by Janssen and Legend Biotech. It is a chimeric antigen receptor (CAR) T-cell therapy directed against B-cell maturation antigen (BCMA), which is a new target for therapies for multiple myeloma.

There are already two other therapies on the market that target BCMA – another CAR T cell, idecabtagene vicleucel (Abecma), which was approved by the FDA in March 2021, and a drug conjugate, belantamab mafodotin (Blenrep), which was approved in August 2020.

The approval of cilta-cel was based on clinical data from the CARTITUDE-1 study, which were initially presented in December 2020 at the annual meeting of the American Society of Hematology, as reported at the time by this news organization.

The trial involved 97 patients with relapsed/refractory multiple myeloma who had already received a median of six previous treatments (range, three to 18), including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

“The treatment journey for the majority of patients living with multiple myeloma is a relentless cycle of remission and relapse, with fewer patients achieving a deep response as they progress through later lines of therapy,” commented Sundar Jagannath, MBBS, professor of medicine, hematology, and medical oncology at Mount Sinai, who was a principal investigator on the pivotal study.

“That is why I have been really excited about the results from the CARTITUDE-1 study, which has demonstrated that cilta-cel can provide deep and durable responses and long-term treatment-free intervals, even in this heavily pretreated multiple myeloma patient population,” he said.

“Today’s approval of Carvykti helps address a great unmet need for these patients,” he commented in a press release from the manufacturer.

Like other CAR T-cell therapies, ciltacabtagene autoleucel is a one-time treatment. It involves collecting blood from the patient, extracting T cells, genetically engineering them, then transfusing them back to the patient, who in the meantime has undergone conditioning.

The results from CARTITUDE-1 show that this one-time treatment resulted in deep and durable responses.

The overall response rate was 98%, and the majority of patients (78%) achieved a stringent complete response, in which physicians are unable to observe any signs or symptoms of disease via imaging or other tests after treatment.

At a median of 18 months’ follow-up, the median duration of response was 21.8 months.

“The responses in the CARTITUDE-1 study showed durability over time and resulted in the majority of heavily pretreated patients achieving deep responses after 18-month follow-up,” commented Mr. Jagannath.

“The approval of cilta-cel provides physicians an immunotherapy treatment option that offers patients an opportunity to be free from anti-myeloma therapies for a period of time,” he added.

As with other CAR T-cell therapies, there were serious side effects, and these products are available only through restricted programs under a risk evaluation and mitigation strategy.

The product information for Cartykti includes a boxed warning that mentions cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome, parkinsonism, Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and prolonged and/or recurrent cytopenias.

The most common adverse reactions (reported in greater than or equal to 20% of patients) are pyrexia, CRS, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections–pathogens unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.

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

A new treatment option for patients with refractory/relapsed multiple myeloma who have already tried four or more therapies has been approved by the U.S. Food and Drug Administration.

The product, ciltacabtagene autoleucel (cilta-cel), will be marketed as Carvykti by Janssen and Legend Biotech. It is a chimeric antigen receptor (CAR) T-cell therapy directed against B-cell maturation antigen (BCMA), which is a new target for therapies for multiple myeloma.

There are already two other therapies on the market that target BCMA – another CAR T cell, idecabtagene vicleucel (Abecma), which was approved by the FDA in March 2021, and a drug conjugate, belantamab mafodotin (Blenrep), which was approved in August 2020.

The approval of cilta-cel was based on clinical data from the CARTITUDE-1 study, which were initially presented in December 2020 at the annual meeting of the American Society of Hematology, as reported at the time by this news organization.

The trial involved 97 patients with relapsed/refractory multiple myeloma who had already received a median of six previous treatments (range, three to 18), including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

“The treatment journey for the majority of patients living with multiple myeloma is a relentless cycle of remission and relapse, with fewer patients achieving a deep response as they progress through later lines of therapy,” commented Sundar Jagannath, MBBS, professor of medicine, hematology, and medical oncology at Mount Sinai, who was a principal investigator on the pivotal study.

“That is why I have been really excited about the results from the CARTITUDE-1 study, which has demonstrated that cilta-cel can provide deep and durable responses and long-term treatment-free intervals, even in this heavily pretreated multiple myeloma patient population,” he said.

“Today’s approval of Carvykti helps address a great unmet need for these patients,” he commented in a press release from the manufacturer.

Like other CAR T-cell therapies, ciltacabtagene autoleucel is a one-time treatment. It involves collecting blood from the patient, extracting T cells, genetically engineering them, then transfusing them back to the patient, who in the meantime has undergone conditioning.

The results from CARTITUDE-1 show that this one-time treatment resulted in deep and durable responses.

The overall response rate was 98%, and the majority of patients (78%) achieved a stringent complete response, in which physicians are unable to observe any signs or symptoms of disease via imaging or other tests after treatment.

At a median of 18 months’ follow-up, the median duration of response was 21.8 months.

“The responses in the CARTITUDE-1 study showed durability over time and resulted in the majority of heavily pretreated patients achieving deep responses after 18-month follow-up,” commented Mr. Jagannath.

“The approval of cilta-cel provides physicians an immunotherapy treatment option that offers patients an opportunity to be free from anti-myeloma therapies for a period of time,” he added.

As with other CAR T-cell therapies, there were serious side effects, and these products are available only through restricted programs under a risk evaluation and mitigation strategy.

The product information for Cartykti includes a boxed warning that mentions cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome, parkinsonism, Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and prolonged and/or recurrent cytopenias.

The most common adverse reactions (reported in greater than or equal to 20% of patients) are pyrexia, CRS, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections–pathogens unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.

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

A new treatment option for patients with refractory/relapsed multiple myeloma who have already tried four or more therapies has been approved by the U.S. Food and Drug Administration.

The product, ciltacabtagene autoleucel (cilta-cel), will be marketed as Carvykti by Janssen and Legend Biotech. It is a chimeric antigen receptor (CAR) T-cell therapy directed against B-cell maturation antigen (BCMA), which is a new target for therapies for multiple myeloma.

There are already two other therapies on the market that target BCMA – another CAR T cell, idecabtagene vicleucel (Abecma), which was approved by the FDA in March 2021, and a drug conjugate, belantamab mafodotin (Blenrep), which was approved in August 2020.

The approval of cilta-cel was based on clinical data from the CARTITUDE-1 study, which were initially presented in December 2020 at the annual meeting of the American Society of Hematology, as reported at the time by this news organization.

The trial involved 97 patients with relapsed/refractory multiple myeloma who had already received a median of six previous treatments (range, three to 18), including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

“The treatment journey for the majority of patients living with multiple myeloma is a relentless cycle of remission and relapse, with fewer patients achieving a deep response as they progress through later lines of therapy,” commented Sundar Jagannath, MBBS, professor of medicine, hematology, and medical oncology at Mount Sinai, who was a principal investigator on the pivotal study.

“That is why I have been really excited about the results from the CARTITUDE-1 study, which has demonstrated that cilta-cel can provide deep and durable responses and long-term treatment-free intervals, even in this heavily pretreated multiple myeloma patient population,” he said.

“Today’s approval of Carvykti helps address a great unmet need for these patients,” he commented in a press release from the manufacturer.

Like other CAR T-cell therapies, ciltacabtagene autoleucel is a one-time treatment. It involves collecting blood from the patient, extracting T cells, genetically engineering them, then transfusing them back to the patient, who in the meantime has undergone conditioning.

The results from CARTITUDE-1 show that this one-time treatment resulted in deep and durable responses.

The overall response rate was 98%, and the majority of patients (78%) achieved a stringent complete response, in which physicians are unable to observe any signs or symptoms of disease via imaging or other tests after treatment.

At a median of 18 months’ follow-up, the median duration of response was 21.8 months.

“The responses in the CARTITUDE-1 study showed durability over time and resulted in the majority of heavily pretreated patients achieving deep responses after 18-month follow-up,” commented Mr. Jagannath.

“The approval of cilta-cel provides physicians an immunotherapy treatment option that offers patients an opportunity to be free from anti-myeloma therapies for a period of time,” he added.

As with other CAR T-cell therapies, there were serious side effects, and these products are available only through restricted programs under a risk evaluation and mitigation strategy.

The product information for Cartykti includes a boxed warning that mentions cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome, parkinsonism, Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and prolonged and/or recurrent cytopenias.

The most common adverse reactions (reported in greater than or equal to 20% of patients) are pyrexia, CRS, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections–pathogens unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.

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

Investigators presenting at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium called for neoadjuvant chemotherapy to be a new standard of care for high-grade upper tract urothelial carcinoma.

They made the call after finding that 63% of patients (36/57) had a pathologic response to gemcitabine/cisplatin before extirpative surgery, with pathologic response defined as less than pT2NO disease on postoperative pathology. Nineteen percent (11/57) had complete responses, with no evidence of the main tumor (ypT0N0).

The approach has a “favorable pathologic response, is well tolerated ... and thus should be considered a new standard of care option,” said investigators led by Wesley Yip, MD, a urologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York.

There was no comparator arm, but the results are in line with previous reports, including a 2014 investigation that found a 5-year disease specific survival (DSS) of 90.1% and 5-year overall survival (OS) of 80.2% among 31 upper tract urothelial carcinoma patients who received neoadjuvant chemotherapy, versus a 5-year DSS and OS of 57.6% among 81 historical controls.

Presentation moderator Stephen Boorjian, MD, chair of urology at the Mayo Clinic in Rochester, Minn., called the findings “valuable” but noted there’s level 1 evidence for an alternative approach, chemotherapy or nivolumab after surgery for patients with particularly worrisome postop pathology. It makes it tough to know if patients should be treated beforehand or afterwards.

“What do we do?” he asked.

Dr. Yip said it’s an open question at this point but that trials are underway to address the issue. In the meantime, “it’s definitely a multidisciplinary discussion to know what’s best for each patient,” he said. One of the factors that argues for the neoadjuvant approach is that substantially fewer patients are eligible for chemotherapy after nephroureterectomy because of diminished renal function. “Patients who might not be eligible ... are the ones we’d be targeting for” neoadjuvant chemotherapy (NAC), he said.

In the study, gemcitabine 1000 mg/m² and cisplatin 35 mg/m² were administered on days 1 and 8 of four 21-day cycles, followed by radical nephroureterectomy or ureterectomy.

Fifty-three of the subjects had high-grade disease by endoscopic biopsy, and the remaining four were enrolled based on imaging and selective cytology. There was no nodal disease on CT within 30 days of neoadjuvant chemotherapy initiation.

Two-year progression-free survival (PFS) was 91% among pathologic responders but only 52% among nonresponders. Every responder was alive at 2 years versus 80% of nonresponders.

Across the entire cohort, 5-year PFS was 61% and 5-year OS 79%; 89.5% of patients were alive at a median follow-up of 3.5 years.

Almost all of the patients completed at least three NAC cycles, and all of them went to surgery, which had a 90-day grade 3 or higher complication rate of 7%.

Sixty-three percent were men, and 95% were White. The median age was 66 years.

The work was funded by the National Institutes of Health and Memorial Sloan Kettering. Dr. Yip had no disclosures. Dr. Boorjian advises ArTara Therapeutics, FerGene, and Ferring.

Investigators presenting at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium called for neoadjuvant chemotherapy to be a new standard of care for high-grade upper tract urothelial carcinoma.

They made the call after finding that 63% of patients (36/57) had a pathologic response to gemcitabine/cisplatin before extirpative surgery, with pathologic response defined as less than pT2NO disease on postoperative pathology. Nineteen percent (11/57) had complete responses, with no evidence of the main tumor (ypT0N0).

The approach has a “favorable pathologic response, is well tolerated ... and thus should be considered a new standard of care option,” said investigators led by Wesley Yip, MD, a urologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York.

There was no comparator arm, but the results are in line with previous reports, including a 2014 investigation that found a 5-year disease specific survival (DSS) of 90.1% and 5-year overall survival (OS) of 80.2% among 31 upper tract urothelial carcinoma patients who received neoadjuvant chemotherapy, versus a 5-year DSS and OS of 57.6% among 81 historical controls.

Presentation moderator Stephen Boorjian, MD, chair of urology at the Mayo Clinic in Rochester, Minn., called the findings “valuable” but noted there’s level 1 evidence for an alternative approach, chemotherapy or nivolumab after surgery for patients with particularly worrisome postop pathology. It makes it tough to know if patients should be treated beforehand or afterwards.

“What do we do?” he asked.

Dr. Yip said it’s an open question at this point but that trials are underway to address the issue. In the meantime, “it’s definitely a multidisciplinary discussion to know what’s best for each patient,” he said. One of the factors that argues for the neoadjuvant approach is that substantially fewer patients are eligible for chemotherapy after nephroureterectomy because of diminished renal function. “Patients who might not be eligible ... are the ones we’d be targeting for” neoadjuvant chemotherapy (NAC), he said.

In the study, gemcitabine 1000 mg/m² and cisplatin 35 mg/m² were administered on days 1 and 8 of four 21-day cycles, followed by radical nephroureterectomy or ureterectomy.

Fifty-three of the subjects had high-grade disease by endoscopic biopsy, and the remaining four were enrolled based on imaging and selective cytology. There was no nodal disease on CT within 30 days of neoadjuvant chemotherapy initiation.

Two-year progression-free survival (PFS) was 91% among pathologic responders but only 52% among nonresponders. Every responder was alive at 2 years versus 80% of nonresponders.

Across the entire cohort, 5-year PFS was 61% and 5-year OS 79%; 89.5% of patients were alive at a median follow-up of 3.5 years.

Almost all of the patients completed at least three NAC cycles, and all of them went to surgery, which had a 90-day grade 3 or higher complication rate of 7%.

Sixty-three percent were men, and 95% were White. The median age was 66 years.

The work was funded by the National Institutes of Health and Memorial Sloan Kettering. Dr. Yip had no disclosures. Dr. Boorjian advises ArTara Therapeutics, FerGene, and Ferring.

Investigators presenting at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium called for neoadjuvant chemotherapy to be a new standard of care for high-grade upper tract urothelial carcinoma.

They made the call after finding that 63% of patients (36/57) had a pathologic response to gemcitabine/cisplatin before extirpative surgery, with pathologic response defined as less than pT2NO disease on postoperative pathology. Nineteen percent (11/57) had complete responses, with no evidence of the main tumor (ypT0N0).

The approach has a “favorable pathologic response, is well tolerated ... and thus should be considered a new standard of care option,” said investigators led by Wesley Yip, MD, a urologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York.

There was no comparator arm, but the results are in line with previous reports, including a 2014 investigation that found a 5-year disease specific survival (DSS) of 90.1% and 5-year overall survival (OS) of 80.2% among 31 upper tract urothelial carcinoma patients who received neoadjuvant chemotherapy, versus a 5-year DSS and OS of 57.6% among 81 historical controls.

Presentation moderator Stephen Boorjian, MD, chair of urology at the Mayo Clinic in Rochester, Minn., called the findings “valuable” but noted there’s level 1 evidence for an alternative approach, chemotherapy or nivolumab after surgery for patients with particularly worrisome postop pathology. It makes it tough to know if patients should be treated beforehand or afterwards.

“What do we do?” he asked.

Dr. Yip said it’s an open question at this point but that trials are underway to address the issue. In the meantime, “it’s definitely a multidisciplinary discussion to know what’s best for each patient,” he said. One of the factors that argues for the neoadjuvant approach is that substantially fewer patients are eligible for chemotherapy after nephroureterectomy because of diminished renal function. “Patients who might not be eligible ... are the ones we’d be targeting for” neoadjuvant chemotherapy (NAC), he said.

In the study, gemcitabine 1000 mg/m² and cisplatin 35 mg/m² were administered on days 1 and 8 of four 21-day cycles, followed by radical nephroureterectomy or ureterectomy.

Fifty-three of the subjects had high-grade disease by endoscopic biopsy, and the remaining four were enrolled based on imaging and selective cytology. There was no nodal disease on CT within 30 days of neoadjuvant chemotherapy initiation.

Two-year progression-free survival (PFS) was 91% among pathologic responders but only 52% among nonresponders. Every responder was alive at 2 years versus 80% of nonresponders.

Across the entire cohort, 5-year PFS was 61% and 5-year OS 79%; 89.5% of patients were alive at a median follow-up of 3.5 years.

Almost all of the patients completed at least three NAC cycles, and all of them went to surgery, which had a 90-day grade 3 or higher complication rate of 7%.

Sixty-three percent were men, and 95% were White. The median age was 66 years.

The work was funded by the National Institutes of Health and Memorial Sloan Kettering. Dr. Yip had no disclosures. Dr. Boorjian advises ArTara Therapeutics, FerGene, and Ferring.

Radiofrequency ablation (RFA) shows efficacy as a potential noninvasive option for the treatment of low-risk microcarcinomas in papillary thyroid cancer (PTC) when measures beyond active surveillance are warranted, results from a new review show.

“The results in the current study suggest that RFA could function as a useful alternative treatment strategy in which patients are treated minimally invasively with curative intentions,” reported the authors of the meta-analysis published online in JAMA Otolaryngology – Head and Neck Surgery.

Commenting on the research, Joanna Klubo-Gwiezdzinska, MD, PhD, said the work offers useful evidence on the potential role for RFA in low-risk micro-PTC – with some notable caveats.

“I agree that RFA might be a good option for patients unwilling or unable to accept active surveillance and for patients who are at high surgical risk because of comorbid conditions,” she told this news organization.

However, “RFA for patients with an evidence of nodule growth requires more data to be analyzed and a longer follow-up period in lieu of the fact that 21% of nodules subjected to RFA did not disappear, based on the data the authors provide,” noted Dr. Klubo-Gwiezdzinska, who is acting chief of thyroid tumors and functional thyroid disorders at the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md.  
 

When active surveillance isn’t enough

Microcarcinoma PTC, defined as measuring 10 mm or less, is highly common, making up approximately half of papillary thyroid cancers diagnosed in some countries, and the outcomes of those cancers are excellent, with disease-specific survival of more than 99% after 10 years.

Guidelines in the United States and Europe typically recommend surgery (lobectomy) as a standard treatment for thyroid cancer, however, with many of the low-risk microcarcinomas remaining indolent and never progressing to the point of requiring treatment over a person’s lifetime, some also recommend considering active surveillance, or watchful waiting, for those lower-risk cancers.

In situations such as evidence of tumor growth during active surveillance, some countries, particularly Asian countries, also suggest considering thermal ablation techniques, including RFA, as an alternative to surgery, with key benefits including lower costs and potentially a lower risk of complications, compared with surgical lobectomy.

Otherwise, RFA is more typically reserved for benign nodules, recurrent PTC, or inoperable disease.
 

New meta-analysis

To investigate reported outcomes with RFA specifically in the treatment of microcarcinoma PTC, the authors, led by Sam P.J. van Dijk, BSc, of University Medical Center Rotterdam (the Netherlands), identified 15 studies published after 2016 involving 1,770 adult patients and 1,822 tumors who received RFA for the treatment of low-risk PTC microcarcinomas, defined as measuring 10 mm or less.

The studies were conducted in China and South Korea, where RFA is more commonly used in low-risk microcarcinoma PTC.

Patients were 77.9% women and a mean age of 45.4 years. The analysis excluded patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension.

Of the 1,822 tumors treated with RFA, 49 required an additional RFA treatment and 1 tumor had two additional treatments.

With a mean follow-up of 33 months (range, 6-131 months), the primary outcome of the pooled rate of complete disappearance of microcarcinoma PTC on ultrasonography was 79%.

The overall rate of tumor progression was 1.5% (26 patients), and local residual microcarcinoma PTC occurred in 0.4% (7 tumors).

New microcarcinoma PTC occurred in 0.9% (15) of patients; 0.2% (4) developed lymph node metastases during follow-up, and no distant metastases were observed.

Minor complications occurred in 45 patients, and there were three major complications, including two voice changes that lasted more than 2 months and one cardiac arrhythmia.

“This study suggests that radiofrequency ablation is a safe and efficient method to treat selected low-risk papillary microcarcinoma of the thyroid,” the researchers said.
 

Questions surrounding the 20% of patients who still had residual nodules

While the analysis did not include direct comparisons between RFA and lobectomy, Dr. Klubo-Gwiezdzinska noted that, in general, “RFA appears to be associated with a lower complication rate compared with surgery, but also lower efficacy, with 21% of patients with residual nodules.”

The results raise the question of whether “all of the residual lesions are associated with persistent disease, and, if so, do they warrant further intervention?” she added.

To that point, the authors noted that only seven (0.4%) of the 21% of patients with persistent nodules showed residual microcarcinoma PTC cells after RFA, a fact that underscores that “the assessment of tumor response in patients with mPTC after RFA is complicated,” they wrote.

A key concern with assessing responses in RFA is that fine needle aspiration has been shown to have reduced diagnostic accuracy following treatment due to insufficient cellularity in the ablation area, the authors noted.

They add that core needle biopsy is believed to have higher accuracy.

While commenting that the analysis used the “best standards,” Dr. Klubo-Gwiezdzinska noted the caveat that it provides “low- to moderate-quality evidence as it included either case series or retrospective cohort studies, characterized by an inherent bias associated with these study designs.”

And as the authors also acknowledge, possible overlap in the included cohorts “could mean that sample sizes might be smaller than reported,” Dr. Klubo-Gwiezdzinska commented.

To further evaluate the pros and cons of RFA, the authors suggested that “future studies may focus on improving complete disappearance rates of the tumor volume, possibly with more advanced or longer RFA procedures.”
 

RFA an option for some patients

In the meantime, senior author Tessa M. van Ginhoven, MD, PhD, of the department of surgical oncology and gastrointestinal surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, suggests that, in addition to cases of local tumor growth, possible uses of RFA for micro-PTC could include situations of patient anxiety due to active surveillance.

“If active surveillance is appropriate for your population, but the patient is anxious and prefers lobectomy, one could envision RFA as a possible adjunct to active surveillance,” she told this news organization.

The authors and Dr. Klubo-Gwiezdzinska reported no relevant financial relationships.

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

Radiofrequency ablation (RFA) shows efficacy as a potential noninvasive option for the treatment of low-risk microcarcinomas in papillary thyroid cancer (PTC) when measures beyond active surveillance are warranted, results from a new review show.

“The results in the current study suggest that RFA could function as a useful alternative treatment strategy in which patients are treated minimally invasively with curative intentions,” reported the authors of the meta-analysis published online in JAMA Otolaryngology – Head and Neck Surgery.

Commenting on the research, Joanna Klubo-Gwiezdzinska, MD, PhD, said the work offers useful evidence on the potential role for RFA in low-risk micro-PTC – with some notable caveats.

“I agree that RFA might be a good option for patients unwilling or unable to accept active surveillance and for patients who are at high surgical risk because of comorbid conditions,” she told this news organization.

However, “RFA for patients with an evidence of nodule growth requires more data to be analyzed and a longer follow-up period in lieu of the fact that 21% of nodules subjected to RFA did not disappear, based on the data the authors provide,” noted Dr. Klubo-Gwiezdzinska, who is acting chief of thyroid tumors and functional thyroid disorders at the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md.  
 

When active surveillance isn’t enough

Microcarcinoma PTC, defined as measuring 10 mm or less, is highly common, making up approximately half of papillary thyroid cancers diagnosed in some countries, and the outcomes of those cancers are excellent, with disease-specific survival of more than 99% after 10 years.

Guidelines in the United States and Europe typically recommend surgery (lobectomy) as a standard treatment for thyroid cancer, however, with many of the low-risk microcarcinomas remaining indolent and never progressing to the point of requiring treatment over a person’s lifetime, some also recommend considering active surveillance, or watchful waiting, for those lower-risk cancers.

In situations such as evidence of tumor growth during active surveillance, some countries, particularly Asian countries, also suggest considering thermal ablation techniques, including RFA, as an alternative to surgery, with key benefits including lower costs and potentially a lower risk of complications, compared with surgical lobectomy.

Otherwise, RFA is more typically reserved for benign nodules, recurrent PTC, or inoperable disease.
 

New meta-analysis

To investigate reported outcomes with RFA specifically in the treatment of microcarcinoma PTC, the authors, led by Sam P.J. van Dijk, BSc, of University Medical Center Rotterdam (the Netherlands), identified 15 studies published after 2016 involving 1,770 adult patients and 1,822 tumors who received RFA for the treatment of low-risk PTC microcarcinomas, defined as measuring 10 mm or less.

The studies were conducted in China and South Korea, where RFA is more commonly used in low-risk microcarcinoma PTC.

Patients were 77.9% women and a mean age of 45.4 years. The analysis excluded patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension.

Of the 1,822 tumors treated with RFA, 49 required an additional RFA treatment and 1 tumor had two additional treatments.

With a mean follow-up of 33 months (range, 6-131 months), the primary outcome of the pooled rate of complete disappearance of microcarcinoma PTC on ultrasonography was 79%.

The overall rate of tumor progression was 1.5% (26 patients), and local residual microcarcinoma PTC occurred in 0.4% (7 tumors).

New microcarcinoma PTC occurred in 0.9% (15) of patients; 0.2% (4) developed lymph node metastases during follow-up, and no distant metastases were observed.

Minor complications occurred in 45 patients, and there were three major complications, including two voice changes that lasted more than 2 months and one cardiac arrhythmia.

“This study suggests that radiofrequency ablation is a safe and efficient method to treat selected low-risk papillary microcarcinoma of the thyroid,” the researchers said.
 

Questions surrounding the 20% of patients who still had residual nodules

While the analysis did not include direct comparisons between RFA and lobectomy, Dr. Klubo-Gwiezdzinska noted that, in general, “RFA appears to be associated with a lower complication rate compared with surgery, but also lower efficacy, with 21% of patients with residual nodules.”

The results raise the question of whether “all of the residual lesions are associated with persistent disease, and, if so, do they warrant further intervention?” she added.

To that point, the authors noted that only seven (0.4%) of the 21% of patients with persistent nodules showed residual microcarcinoma PTC cells after RFA, a fact that underscores that “the assessment of tumor response in patients with mPTC after RFA is complicated,” they wrote.

A key concern with assessing responses in RFA is that fine needle aspiration has been shown to have reduced diagnostic accuracy following treatment due to insufficient cellularity in the ablation area, the authors noted.

They add that core needle biopsy is believed to have higher accuracy.

While commenting that the analysis used the “best standards,” Dr. Klubo-Gwiezdzinska noted the caveat that it provides “low- to moderate-quality evidence as it included either case series or retrospective cohort studies, characterized by an inherent bias associated with these study designs.”

And as the authors also acknowledge, possible overlap in the included cohorts “could mean that sample sizes might be smaller than reported,” Dr. Klubo-Gwiezdzinska commented.

To further evaluate the pros and cons of RFA, the authors suggested that “future studies may focus on improving complete disappearance rates of the tumor volume, possibly with more advanced or longer RFA procedures.”
 

RFA an option for some patients

In the meantime, senior author Tessa M. van Ginhoven, MD, PhD, of the department of surgical oncology and gastrointestinal surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, suggests that, in addition to cases of local tumor growth, possible uses of RFA for micro-PTC could include situations of patient anxiety due to active surveillance.

“If active surveillance is appropriate for your population, but the patient is anxious and prefers lobectomy, one could envision RFA as a possible adjunct to active surveillance,” she told this news organization.

The authors and Dr. Klubo-Gwiezdzinska reported no relevant financial relationships.

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

Radiofrequency ablation (RFA) shows efficacy as a potential noninvasive option for the treatment of low-risk microcarcinomas in papillary thyroid cancer (PTC) when measures beyond active surveillance are warranted, results from a new review show.

“The results in the current study suggest that RFA could function as a useful alternative treatment strategy in which patients are treated minimally invasively with curative intentions,” reported the authors of the meta-analysis published online in JAMA Otolaryngology – Head and Neck Surgery.

Commenting on the research, Joanna Klubo-Gwiezdzinska, MD, PhD, said the work offers useful evidence on the potential role for RFA in low-risk micro-PTC – with some notable caveats.

“I agree that RFA might be a good option for patients unwilling or unable to accept active surveillance and for patients who are at high surgical risk because of comorbid conditions,” she told this news organization.

However, “RFA for patients with an evidence of nodule growth requires more data to be analyzed and a longer follow-up period in lieu of the fact that 21% of nodules subjected to RFA did not disappear, based on the data the authors provide,” noted Dr. Klubo-Gwiezdzinska, who is acting chief of thyroid tumors and functional thyroid disorders at the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md.  
 

When active surveillance isn’t enough

Microcarcinoma PTC, defined as measuring 10 mm or less, is highly common, making up approximately half of papillary thyroid cancers diagnosed in some countries, and the outcomes of those cancers are excellent, with disease-specific survival of more than 99% after 10 years.

Guidelines in the United States and Europe typically recommend surgery (lobectomy) as a standard treatment for thyroid cancer, however, with many of the low-risk microcarcinomas remaining indolent and never progressing to the point of requiring treatment over a person’s lifetime, some also recommend considering active surveillance, or watchful waiting, for those lower-risk cancers.

In situations such as evidence of tumor growth during active surveillance, some countries, particularly Asian countries, also suggest considering thermal ablation techniques, including RFA, as an alternative to surgery, with key benefits including lower costs and potentially a lower risk of complications, compared with surgical lobectomy.

Otherwise, RFA is more typically reserved for benign nodules, recurrent PTC, or inoperable disease.
 

New meta-analysis

To investigate reported outcomes with RFA specifically in the treatment of microcarcinoma PTC, the authors, led by Sam P.J. van Dijk, BSc, of University Medical Center Rotterdam (the Netherlands), identified 15 studies published after 2016 involving 1,770 adult patients and 1,822 tumors who received RFA for the treatment of low-risk PTC microcarcinomas, defined as measuring 10 mm or less.

The studies were conducted in China and South Korea, where RFA is more commonly used in low-risk microcarcinoma PTC.

Patients were 77.9% women and a mean age of 45.4 years. The analysis excluded patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension.

Of the 1,822 tumors treated with RFA, 49 required an additional RFA treatment and 1 tumor had two additional treatments.

With a mean follow-up of 33 months (range, 6-131 months), the primary outcome of the pooled rate of complete disappearance of microcarcinoma PTC on ultrasonography was 79%.

The overall rate of tumor progression was 1.5% (26 patients), and local residual microcarcinoma PTC occurred in 0.4% (7 tumors).

New microcarcinoma PTC occurred in 0.9% (15) of patients; 0.2% (4) developed lymph node metastases during follow-up, and no distant metastases were observed.

Minor complications occurred in 45 patients, and there were three major complications, including two voice changes that lasted more than 2 months and one cardiac arrhythmia.

“This study suggests that radiofrequency ablation is a safe and efficient method to treat selected low-risk papillary microcarcinoma of the thyroid,” the researchers said.
 

Questions surrounding the 20% of patients who still had residual nodules

While the analysis did not include direct comparisons between RFA and lobectomy, Dr. Klubo-Gwiezdzinska noted that, in general, “RFA appears to be associated with a lower complication rate compared with surgery, but also lower efficacy, with 21% of patients with residual nodules.”

The results raise the question of whether “all of the residual lesions are associated with persistent disease, and, if so, do they warrant further intervention?” she added.

To that point, the authors noted that only seven (0.4%) of the 21% of patients with persistent nodules showed residual microcarcinoma PTC cells after RFA, a fact that underscores that “the assessment of tumor response in patients with mPTC after RFA is complicated,” they wrote.

A key concern with assessing responses in RFA is that fine needle aspiration has been shown to have reduced diagnostic accuracy following treatment due to insufficient cellularity in the ablation area, the authors noted.

They add that core needle biopsy is believed to have higher accuracy.

While commenting that the analysis used the “best standards,” Dr. Klubo-Gwiezdzinska noted the caveat that it provides “low- to moderate-quality evidence as it included either case series or retrospective cohort studies, characterized by an inherent bias associated with these study designs.”

And as the authors also acknowledge, possible overlap in the included cohorts “could mean that sample sizes might be smaller than reported,” Dr. Klubo-Gwiezdzinska commented.

To further evaluate the pros and cons of RFA, the authors suggested that “future studies may focus on improving complete disappearance rates of the tumor volume, possibly with more advanced or longer RFA procedures.”
 

RFA an option for some patients

In the meantime, senior author Tessa M. van Ginhoven, MD, PhD, of the department of surgical oncology and gastrointestinal surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, suggests that, in addition to cases of local tumor growth, possible uses of RFA for micro-PTC could include situations of patient anxiety due to active surveillance.

“If active surveillance is appropriate for your population, but the patient is anxious and prefers lobectomy, one could envision RFA as a possible adjunct to active surveillance,” she told this news organization.

The authors and Dr. Klubo-Gwiezdzinska reported no relevant financial relationships.

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

Breast cancer risk genes are generally associated with triple-negative and high-grade disease, but differ substantially in their associated pathology, a large case-control analysis shows.

The findings have potential implications for genetic testing, risk prediction, variant classification, and screening, the authors noted.

To assess links between pathogenic germline variants in nine major breast cancer (BC) susceptibility genes and pathological features of nonmetastasized breast tumors, investigators from the Breast Cancer Association Consortium compared 42,680 women with breast cancer and 42,387 population-matched controls from the BRIDGES large-scale sequencing study.

They looked specifically at features relevant to prognosis and distinct therapeutic options, including tumor subtype, morphology, size, stage, and lymph node involvement, and found substantial differences in tumor subtype distribution by gene.

“Pathogenic [protein-truncating variants and pathogenic missense variants] in these ... susceptibility genes were disproportionately associated with more aggressive breast caner, particularly among younger women,” they wrote, noting that carriers of rare genetic variants in the nine genes comprised more than 27% of women diagnosed at age 40 or younger with triple-negative disease (driven mainly by BRCA1) and about 16% of those diagnosed with hormone receptor (HR)–positive, HER2-negative high-grade disease.

All together, the nine genes were associated with 14.4% of tumors in women aged 40 years and younger, but less than 4% in women over age 60 years, and among younger women, the prevalence of variants combined was higher in those with triple-negative and HR-positive, HER2-negative disease versus other subtypes, they said.

The findings were published online on Jan. 27, 2022, in JAMA Oncology.

Study subjects were women aged 18-79 years who were sampled, independently of family history, from 38 international population- or hospital-based studies conducted between 1991 and 2016.

The genes assessed included ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53.

Substantial heterogeneity was observed in the distribution of intrinsic subtypes by gene. For example, RAD51C, RAD51D, and BARD1 variants were associated mainly with triple-negative disease (odds ratios, 6.19, 6.19, and 10.05 respectively), and CHEK2 variants were associated with all subtypes (with ORs ranging from 2.21-3.17) except for triple-negative disease, the authors found.

“For ATM variants, the association was strongest for [HR-positive, HER2-negative]high-grade subtype (OR, 4.99). BRCA1 was associated with increased risk of all subtypes, but the ORs varied widely, being highest for triple-negative disease (OR, 55.32),” they wrote.

BRCA2 and PALB2 variants were also associated with triple-negative disease, TP53 variants were most strongly associated with HR-positive, HER2-negative and HR-negative, HER2-positive subtypes, and tumors occurring in pathogenic variant carriers were of higher grade, they added, noting that for most genes and subtypes, a decline in ORs was observed with increasing age.

All genes except CHEK2 were more strongly associated with high-grade disease.

These and other findings from the study can “inform guidelines for eligibility for gene panel sequencing and breast cancer surveillance in the general population,” the authors explained, adding that tumor characteristics can also be used to determine whether variants of uncertain significance are likely to be pathogenic.

The data should therefore “improve the precision of variant classification algorithms and extend them to a larger set of genes,” they noted.

“This case-control study suggests that rare variants in BC susceptibility genes display marked heterogeneity with respect to tumor phenotype, but also similarities between genes that are consistent with known biological functions. This present study provides detailed quantification of subtype-specific breast cancer risks; these can potentially improve risk prediction models and breast cancer prevention strategies,” they concluded.

More specifically, women found to be carrying variants in these genes may be offered enhanced screening, including by MRI, risk-reducing surgery, chemoprevention, and genetic counseling, corresponding author Nasim Mavaddat, MBBS, PhD, explained in an interview.

“Understanding tumor pathology associated with the genes can inform breast cancer risk prediction models, and management and treatment of women harboring pathogenic variants,” she noted.

The findings “enhance our understanding of breast cancer biology and aid efforts to classify whether genetic variants of uncertain significance are also likely to be pathogenic,” added Dr. Mavaddat, a senior research associate at the University of Cambridge (England).

She also said the investigators are taking steps to include the results in “CanRisk,” a cancer risk prediction model used by genetic counselors and other clinicians, and are “exploring whether variants in these genes are associated with contralateral breast cancer risk and survival after a breast cancer.”

As most participants were European, analyses should be extended to women of other racial and ethnic groups, she added.

The BRIDGES panel sequencing was supported by the European Union Horizon 2020 research and innovation program BRIDGES and the Wellcome Trust. The Breast Cancer Association Consortium is also funded by the European Union Horizon 2020 research and innovation program, the PERSPECTIVE I&I project, which is funded by the Government of Canada, and the Confluence project, which is funded with intramural funds from the National Cancer Institute. Dr. Mavaddat reported grants from the University of Cambridge, European Union Horizon 2020, Wellcome Trust, Genome Canada, Canadian Institutes of Health Research, and National Cancer Institute during the conduct of the study.

Breast cancer risk genes are generally associated with triple-negative and high-grade disease, but differ substantially in their associated pathology, a large case-control analysis shows.

The findings have potential implications for genetic testing, risk prediction, variant classification, and screening, the authors noted.

To assess links between pathogenic germline variants in nine major breast cancer (BC) susceptibility genes and pathological features of nonmetastasized breast tumors, investigators from the Breast Cancer Association Consortium compared 42,680 women with breast cancer and 42,387 population-matched controls from the BRIDGES large-scale sequencing study.

They looked specifically at features relevant to prognosis and distinct therapeutic options, including tumor subtype, morphology, size, stage, and lymph node involvement, and found substantial differences in tumor subtype distribution by gene.

“Pathogenic [protein-truncating variants and pathogenic missense variants] in these ... susceptibility genes were disproportionately associated with more aggressive breast caner, particularly among younger women,” they wrote, noting that carriers of rare genetic variants in the nine genes comprised more than 27% of women diagnosed at age 40 or younger with triple-negative disease (driven mainly by BRCA1) and about 16% of those diagnosed with hormone receptor (HR)–positive, HER2-negative high-grade disease.

All together, the nine genes were associated with 14.4% of tumors in women aged 40 years and younger, but less than 4% in women over age 60 years, and among younger women, the prevalence of variants combined was higher in those with triple-negative and HR-positive, HER2-negative disease versus other subtypes, they said.

The findings were published online on Jan. 27, 2022, in JAMA Oncology.

Study subjects were women aged 18-79 years who were sampled, independently of family history, from 38 international population- or hospital-based studies conducted between 1991 and 2016.

The genes assessed included ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53.

Substantial heterogeneity was observed in the distribution of intrinsic subtypes by gene. For example, RAD51C, RAD51D, and BARD1 variants were associated mainly with triple-negative disease (odds ratios, 6.19, 6.19, and 10.05 respectively), and CHEK2 variants were associated with all subtypes (with ORs ranging from 2.21-3.17) except for triple-negative disease, the authors found.

“For ATM variants, the association was strongest for [HR-positive, HER2-negative]high-grade subtype (OR, 4.99). BRCA1 was associated with increased risk of all subtypes, but the ORs varied widely, being highest for triple-negative disease (OR, 55.32),” they wrote.

BRCA2 and PALB2 variants were also associated with triple-negative disease, TP53 variants were most strongly associated with HR-positive, HER2-negative and HR-negative, HER2-positive subtypes, and tumors occurring in pathogenic variant carriers were of higher grade, they added, noting that for most genes and subtypes, a decline in ORs was observed with increasing age.

All genes except CHEK2 were more strongly associated with high-grade disease.

These and other findings from the study can “inform guidelines for eligibility for gene panel sequencing and breast cancer surveillance in the general population,” the authors explained, adding that tumor characteristics can also be used to determine whether variants of uncertain significance are likely to be pathogenic.

The data should therefore “improve the precision of variant classification algorithms and extend them to a larger set of genes,” they noted.

“This case-control study suggests that rare variants in BC susceptibility genes display marked heterogeneity with respect to tumor phenotype, but also similarities between genes that are consistent with known biological functions. This present study provides detailed quantification of subtype-specific breast cancer risks; these can potentially improve risk prediction models and breast cancer prevention strategies,” they concluded.

More specifically, women found to be carrying variants in these genes may be offered enhanced screening, including by MRI, risk-reducing surgery, chemoprevention, and genetic counseling, corresponding author Nasim Mavaddat, MBBS, PhD, explained in an interview.

“Understanding tumor pathology associated with the genes can inform breast cancer risk prediction models, and management and treatment of women harboring pathogenic variants,” she noted.

The findings “enhance our understanding of breast cancer biology and aid efforts to classify whether genetic variants of uncertain significance are also likely to be pathogenic,” added Dr. Mavaddat, a senior research associate at the University of Cambridge (England).

She also said the investigators are taking steps to include the results in “CanRisk,” a cancer risk prediction model used by genetic counselors and other clinicians, and are “exploring whether variants in these genes are associated with contralateral breast cancer risk and survival after a breast cancer.”

As most participants were European, analyses should be extended to women of other racial and ethnic groups, she added.

The BRIDGES panel sequencing was supported by the European Union Horizon 2020 research and innovation program BRIDGES and the Wellcome Trust. The Breast Cancer Association Consortium is also funded by the European Union Horizon 2020 research and innovation program, the PERSPECTIVE I&I project, which is funded by the Government of Canada, and the Confluence project, which is funded with intramural funds from the National Cancer Institute. Dr. Mavaddat reported grants from the University of Cambridge, European Union Horizon 2020, Wellcome Trust, Genome Canada, Canadian Institutes of Health Research, and National Cancer Institute during the conduct of the study.

Breast cancer risk genes are generally associated with triple-negative and high-grade disease, but differ substantially in their associated pathology, a large case-control analysis shows.

The findings have potential implications for genetic testing, risk prediction, variant classification, and screening, the authors noted.

To assess links between pathogenic germline variants in nine major breast cancer (BC) susceptibility genes and pathological features of nonmetastasized breast tumors, investigators from the Breast Cancer Association Consortium compared 42,680 women with breast cancer and 42,387 population-matched controls from the BRIDGES large-scale sequencing study.

They looked specifically at features relevant to prognosis and distinct therapeutic options, including tumor subtype, morphology, size, stage, and lymph node involvement, and found substantial differences in tumor subtype distribution by gene.

“Pathogenic [protein-truncating variants and pathogenic missense variants] in these ... susceptibility genes were disproportionately associated with more aggressive breast caner, particularly among younger women,” they wrote, noting that carriers of rare genetic variants in the nine genes comprised more than 27% of women diagnosed at age 40 or younger with triple-negative disease (driven mainly by BRCA1) and about 16% of those diagnosed with hormone receptor (HR)–positive, HER2-negative high-grade disease.

All together, the nine genes were associated with 14.4% of tumors in women aged 40 years and younger, but less than 4% in women over age 60 years, and among younger women, the prevalence of variants combined was higher in those with triple-negative and HR-positive, HER2-negative disease versus other subtypes, they said.

The findings were published online on Jan. 27, 2022, in JAMA Oncology.

Study subjects were women aged 18-79 years who were sampled, independently of family history, from 38 international population- or hospital-based studies conducted between 1991 and 2016.

The genes assessed included ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53.

Substantial heterogeneity was observed in the distribution of intrinsic subtypes by gene. For example, RAD51C, RAD51D, and BARD1 variants were associated mainly with triple-negative disease (odds ratios, 6.19, 6.19, and 10.05 respectively), and CHEK2 variants were associated with all subtypes (with ORs ranging from 2.21-3.17) except for triple-negative disease, the authors found.

“For ATM variants, the association was strongest for [HR-positive, HER2-negative]high-grade subtype (OR, 4.99). BRCA1 was associated with increased risk of all subtypes, but the ORs varied widely, being highest for triple-negative disease (OR, 55.32),” they wrote.

BRCA2 and PALB2 variants were also associated with triple-negative disease, TP53 variants were most strongly associated with HR-positive, HER2-negative and HR-negative, HER2-positive subtypes, and tumors occurring in pathogenic variant carriers were of higher grade, they added, noting that for most genes and subtypes, a decline in ORs was observed with increasing age.

All genes except CHEK2 were more strongly associated with high-grade disease.

These and other findings from the study can “inform guidelines for eligibility for gene panel sequencing and breast cancer surveillance in the general population,” the authors explained, adding that tumor characteristics can also be used to determine whether variants of uncertain significance are likely to be pathogenic.

The data should therefore “improve the precision of variant classification algorithms and extend them to a larger set of genes,” they noted.

“This case-control study suggests that rare variants in BC susceptibility genes display marked heterogeneity with respect to tumor phenotype, but also similarities between genes that are consistent with known biological functions. This present study provides detailed quantification of subtype-specific breast cancer risks; these can potentially improve risk prediction models and breast cancer prevention strategies,” they concluded.

More specifically, women found to be carrying variants in these genes may be offered enhanced screening, including by MRI, risk-reducing surgery, chemoprevention, and genetic counseling, corresponding author Nasim Mavaddat, MBBS, PhD, explained in an interview.

“Understanding tumor pathology associated with the genes can inform breast cancer risk prediction models, and management and treatment of women harboring pathogenic variants,” she noted.

The findings “enhance our understanding of breast cancer biology and aid efforts to classify whether genetic variants of uncertain significance are also likely to be pathogenic,” added Dr. Mavaddat, a senior research associate at the University of Cambridge (England).

She also said the investigators are taking steps to include the results in “CanRisk,” a cancer risk prediction model used by genetic counselors and other clinicians, and are “exploring whether variants in these genes are associated with contralateral breast cancer risk and survival after a breast cancer.”

As most participants were European, analyses should be extended to women of other racial and ethnic groups, she added.

The BRIDGES panel sequencing was supported by the European Union Horizon 2020 research and innovation program BRIDGES and the Wellcome Trust. The Breast Cancer Association Consortium is also funded by the European Union Horizon 2020 research and innovation program, the PERSPECTIVE I&I project, which is funded by the Government of Canada, and the Confluence project, which is funded with intramural funds from the National Cancer Institute. Dr. Mavaddat reported grants from the University of Cambridge, European Union Horizon 2020, Wellcome Trust, Genome Canada, Canadian Institutes of Health Research, and National Cancer Institute during the conduct of the study.

There was a remarkable reduction in bowel and urinary side effects when MRI was used instead of CT to guide stereotactic body radiotherapy (SBRT) for localized prostate cancer, shows a study from the University of California, Los Angeles.

Among the first 100 men in the phase 3 MIRAGE trial (Magnetic Resonance Imaging–Guided Versus Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer), MRI guidance more than halved the incidence of grade 2 or higher physician-reported genitourinary toxicity within 90 days of the procedure, which fell from 47.1% with CT to 22.4% with MRI.

While 13.7% of men had gastrointestinal complications with CT guidance, there wasn’t a single case in the MRI arm. The findings were presented Feb. 17 at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

The investigators thought they’d need 300 men to detect a safety difference, but the results are so strong that they’ve scaled back enrollment to 154. In the meantime, MRI-guided SBRT is now offered routinely to men with localized prostate cancer at UCLA.

“Our final results are expected later this year, but we are extremely optimistic by what we’re seeing, and hope this technology will soon begin to offer men undergoing radiotherapy for prostate cancer better outcomes,” said lead investigator Amar Upadhyaya Kishan, MD, a genitourinary oncology radiologist, in a UCLA press release.

The better outcomes are caused by the enhanced imaging capabilities of MRI, including real time tracking and automatic beam shutoff when the prostate moves too far outside of the treatment boundary, Dr. Kishan explained on Twitter.

Because of the extra precision, “we felt we could safely reduce the planning margins to only 2 mm” with MRI, down from 4 mm with CT. It translated to smaller treatment volumes and less collateral tissue damage, he said.

Across the first 100 subjects, 49 men were randomized to MRI-guided SBRT and 51 to SBRT with CT guidance. Their prostates and proximal seminal vesicles were dosed with 40 Gy of radiation in five fractions. Rectal spacing and nodal irradiation were at physician discretion.

Patients in the MRI arm also reported significantly fewer urinary symptoms, including urgency, incontinence, burning sensations, and bowel dysfunction, such as pain, diarrhea, and obstruction, among others, at 1 month with MRI guidance. The differences diminished at 3 months with adverse event management in the CT arm.

Lymph nodes were irradiated in 29% of men in the CT group versus 20% in the MRI arm, and 37% of the CT group versus 27% with MRI had rectal spacing.

Baseline gland size was a median of 39 mL in both groups. Baseline International Prostate Symptom Scores were a median of 8 points in the MRI group but 5 points in the CT arm.

The work was funded by UCLA, among others. Dr. Kishan has ownership interests in ViewRay, the company that makes the MRI-guiding technology used in the trial, and reported honoraria and research funding from the company.

There was a remarkable reduction in bowel and urinary side effects when MRI was used instead of CT to guide stereotactic body radiotherapy (SBRT) for localized prostate cancer, shows a study from the University of California, Los Angeles.

Among the first 100 men in the phase 3 MIRAGE trial (Magnetic Resonance Imaging–Guided Versus Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer), MRI guidance more than halved the incidence of grade 2 or higher physician-reported genitourinary toxicity within 90 days of the procedure, which fell from 47.1% with CT to 22.4% with MRI.

While 13.7% of men had gastrointestinal complications with CT guidance, there wasn’t a single case in the MRI arm. The findings were presented Feb. 17 at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

The investigators thought they’d need 300 men to detect a safety difference, but the results are so strong that they’ve scaled back enrollment to 154. In the meantime, MRI-guided SBRT is now offered routinely to men with localized prostate cancer at UCLA.

“Our final results are expected later this year, but we are extremely optimistic by what we’re seeing, and hope this technology will soon begin to offer men undergoing radiotherapy for prostate cancer better outcomes,” said lead investigator Amar Upadhyaya Kishan, MD, a genitourinary oncology radiologist, in a UCLA press release.

The better outcomes are caused by the enhanced imaging capabilities of MRI, including real time tracking and automatic beam shutoff when the prostate moves too far outside of the treatment boundary, Dr. Kishan explained on Twitter.

Because of the extra precision, “we felt we could safely reduce the planning margins to only 2 mm” with MRI, down from 4 mm with CT. It translated to smaller treatment volumes and less collateral tissue damage, he said.

Across the first 100 subjects, 49 men were randomized to MRI-guided SBRT and 51 to SBRT with CT guidance. Their prostates and proximal seminal vesicles were dosed with 40 Gy of radiation in five fractions. Rectal spacing and nodal irradiation were at physician discretion.

Patients in the MRI arm also reported significantly fewer urinary symptoms, including urgency, incontinence, burning sensations, and bowel dysfunction, such as pain, diarrhea, and obstruction, among others, at 1 month with MRI guidance. The differences diminished at 3 months with adverse event management in the CT arm.

Lymph nodes were irradiated in 29% of men in the CT group versus 20% in the MRI arm, and 37% of the CT group versus 27% with MRI had rectal spacing.

Baseline gland size was a median of 39 mL in both groups. Baseline International Prostate Symptom Scores were a median of 8 points in the MRI group but 5 points in the CT arm.

The work was funded by UCLA, among others. Dr. Kishan has ownership interests in ViewRay, the company that makes the MRI-guiding technology used in the trial, and reported honoraria and research funding from the company.

There was a remarkable reduction in bowel and urinary side effects when MRI was used instead of CT to guide stereotactic body radiotherapy (SBRT) for localized prostate cancer, shows a study from the University of California, Los Angeles.

Among the first 100 men in the phase 3 MIRAGE trial (Magnetic Resonance Imaging–Guided Versus Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer), MRI guidance more than halved the incidence of grade 2 or higher physician-reported genitourinary toxicity within 90 days of the procedure, which fell from 47.1% with CT to 22.4% with MRI.

While 13.7% of men had gastrointestinal complications with CT guidance, there wasn’t a single case in the MRI arm. The findings were presented Feb. 17 at the American Society of Clinical Oncology Genitourinary Cancers Symposium.

The investigators thought they’d need 300 men to detect a safety difference, but the results are so strong that they’ve scaled back enrollment to 154. In the meantime, MRI-guided SBRT is now offered routinely to men with localized prostate cancer at UCLA.

“Our final results are expected later this year, but we are extremely optimistic by what we’re seeing, and hope this technology will soon begin to offer men undergoing radiotherapy for prostate cancer better outcomes,” said lead investigator Amar Upadhyaya Kishan, MD, a genitourinary oncology radiologist, in a UCLA press release.

The better outcomes are caused by the enhanced imaging capabilities of MRI, including real time tracking and automatic beam shutoff when the prostate moves too far outside of the treatment boundary, Dr. Kishan explained on Twitter.

Because of the extra precision, “we felt we could safely reduce the planning margins to only 2 mm” with MRI, down from 4 mm with CT. It translated to smaller treatment volumes and less collateral tissue damage, he said.

Across the first 100 subjects, 49 men were randomized to MRI-guided SBRT and 51 to SBRT with CT guidance. Their prostates and proximal seminal vesicles were dosed with 40 Gy of radiation in five fractions. Rectal spacing and nodal irradiation were at physician discretion.

Patients in the MRI arm also reported significantly fewer urinary symptoms, including urgency, incontinence, burning sensations, and bowel dysfunction, such as pain, diarrhea, and obstruction, among others, at 1 month with MRI guidance. The differences diminished at 3 months with adverse event management in the CT arm.

Lymph nodes were irradiated in 29% of men in the CT group versus 20% in the MRI arm, and 37% of the CT group versus 27% with MRI had rectal spacing.

Baseline gland size was a median of 39 mL in both groups. Baseline International Prostate Symptom Scores were a median of 8 points in the MRI group but 5 points in the CT arm.

The work was funded by UCLA, among others. Dr. Kishan has ownership interests in ViewRay, the company that makes the MRI-guiding technology used in the trial, and reported honoraria and research funding from the company.

Women with early-stage breast cancer who are poorly represented in clinical trials have worse survival than their well-represented peers, according to a real-world analysis.

The study shows that more than half of women with early breast cancer are not well represented in clinical trials because of age, comorbidities, or race, yet they receive therapies based on the results of these trials.

“The most interesting finding is that patients with comorbidities resulting in lab abnormalities that would typically exclude them from receiving medication on a trial are still frequently receiving these medications and have an almost threefold higher mortality,” Gabrielle Rocque, MD, with the division of hematology and oncology, University of Alabama at Birmingham, told this news organization.

“We need to do a deeper dive to better understand what is driving this mortality difference and test specific medications in patients with these conditions to understand the optimal treatment for this population,” Dr. Rocque added.

The study was published Feb. 1 in JCO Oncology Practice.

Many patient groups are not well represented in clinical trials, including patients of color, older patients, and those with comorbidities, and it remains unclear how treatment outcomes may differ among these patients, compared with those who are well represented in trials.

To investigate, Dr. Rocque and colleagues looked at 11,770 women diagnosed with stage I-III breast cancer between 2005 and 2015 in the American Society of Clinical Oncology CancerLinQ database.

White women between 45 and 69 years of age with no comorbid conditions were considered well represented and made up 48% of the cohort.

Non-White women and/or those younger than 45 years or older than 70 were considered under represented and made up 45% of the cohort. The unrepresented group (7%) included women with comorbidities – such as liver disease, renal insufficiency, thrombocytopenia, anemia, or uncontrolled diabetes – or concurrent cancer.

The majority of the women received a high-intensity chemotherapy regimen, including 58% of unrepresented, 66% of underrepresented, and 63% of well-represented patients.

Compared with well-represented women, unrepresented women had a higher risk of death at 5 years (adjusted hazard ratio, 2.71; 95% confidence interval, 2.08-3.52).

Overall, the team found no significant increase in the risk of death at 5 years in underrepresented vs. well-represented women (aHR, 1.19; 95% CI, 0.98-1.45). However, that risk varied with age. Among underrepresented women, those aged 70 and older had more than a twofold higher risk of 5-year mortality (aHR, 2.21), while those younger than 45 had a lower risk of 5-year mortality (aHR, 0.63), compared with those aged 45-69 years.

For three cancer subtypes, unrepresented patients had a greater than twofold higher risk of 5-year mortality, compared with well-represented patients (aHR, 2.50 for HER2-positive disease; aHR, 2.54 for HR-positive/HER2-negative disease; and aHR, 2.75 for triple-negative disease).

Underrepresented patients with HR-positive/HER2-negative disease had a 38% increased risk of 5-year mortality, compared with their well-represented peers (aHR, 1.38). However, there were no significant differences in 5-year mortality for underrepresented vs. well-represented patients with HER2-positive or triple-negative subtypes.
 

Risky business?

This analysis shows that unrepresented populations receive common treatment regimens at a similar rate as well-represented patients, the researchers note.

“By excluding patients with differing clinical conditions from trials but including them in the population to which drugs can be disseminated, one runs the risk of inadvertently causing injury,” the authors caution.

“To inform the practice of evidence-based medicine in an equitable manner, our findings support a need to both expand clinical trial inclusion criteria and report on clinical trial outcomes by clinical and demographic characteristics,” Dr. Rocque and colleagues conclude.

Charles Shapiro, MD, professor of medicine, hematology, and medical oncology, Icahn School of Medicine at Mount Sinai, New York, is not surprised by the findings of this study.

“We know that clinical trials are too restrictive and include only a selected population largely without comorbidities, but in the real world, people have comorbidities,” Dr. Shapiro, who was not involved in the research, told this news organization.

The study “starkly illustrates” the poorer survival of populations not represented in clinical trials.

“It could be that we need to change clinical trials, maybe ask fewer questions or maybe ask more important questions and loosen the eligibility up, because in the real world, there are people with comorbidities and people who are over 70,” Dr. Shapiro stated.

Are strides being made to change that? “Not really,” Dr. Shapiro said in an interview.

The study was supported by grants from the Robert Wood Johnson Foundation and the American Cancer Society. Dr. Rocque has served as a consultant or advisor for Pfizer; has received research funding from Carevive Systems, Genentech, and Pfizer; and has received travel, accommodations, and expenses from Carevive. Dr. Shapiro has financial relationships with UptoDate, 2nd MD, and Anthenum.

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

Women with early-stage breast cancer who are poorly represented in clinical trials have worse survival than their well-represented peers, according to a real-world analysis.

The study shows that more than half of women with early breast cancer are not well represented in clinical trials because of age, comorbidities, or race, yet they receive therapies based on the results of these trials.

“The most interesting finding is that patients with comorbidities resulting in lab abnormalities that would typically exclude them from receiving medication on a trial are still frequently receiving these medications and have an almost threefold higher mortality,” Gabrielle Rocque, MD, with the division of hematology and oncology, University of Alabama at Birmingham, told this news organization.

“We need to do a deeper dive to better understand what is driving this mortality difference and test specific medications in patients with these conditions to understand the optimal treatment for this population,” Dr. Rocque added.

The study was published Feb. 1 in JCO Oncology Practice.

Many patient groups are not well represented in clinical trials, including patients of color, older patients, and those with comorbidities, and it remains unclear how treatment outcomes may differ among these patients, compared with those who are well represented in trials.

To investigate, Dr. Rocque and colleagues looked at 11,770 women diagnosed with stage I-III breast cancer between 2005 and 2015 in the American Society of Clinical Oncology CancerLinQ database.

White women between 45 and 69 years of age with no comorbid conditions were considered well represented and made up 48% of the cohort.

Non-White women and/or those younger than 45 years or older than 70 were considered under represented and made up 45% of the cohort. The unrepresented group (7%) included women with comorbidities – such as liver disease, renal insufficiency, thrombocytopenia, anemia, or uncontrolled diabetes – or concurrent cancer.

The majority of the women received a high-intensity chemotherapy regimen, including 58% of unrepresented, 66% of underrepresented, and 63% of well-represented patients.

Compared with well-represented women, unrepresented women had a higher risk of death at 5 years (adjusted hazard ratio, 2.71; 95% confidence interval, 2.08-3.52).

Overall, the team found no significant increase in the risk of death at 5 years in underrepresented vs. well-represented women (aHR, 1.19; 95% CI, 0.98-1.45). However, that risk varied with age. Among underrepresented women, those aged 70 and older had more than a twofold higher risk of 5-year mortality (aHR, 2.21), while those younger than 45 had a lower risk of 5-year mortality (aHR, 0.63), compared with those aged 45-69 years.

For three cancer subtypes, unrepresented patients had a greater than twofold higher risk of 5-year mortality, compared with well-represented patients (aHR, 2.50 for HER2-positive disease; aHR, 2.54 for HR-positive/HER2-negative disease; and aHR, 2.75 for triple-negative disease).

Underrepresented patients with HR-positive/HER2-negative disease had a 38% increased risk of 5-year mortality, compared with their well-represented peers (aHR, 1.38). However, there were no significant differences in 5-year mortality for underrepresented vs. well-represented patients with HER2-positive or triple-negative subtypes.
 

Risky business?

This analysis shows that unrepresented populations receive common treatment regimens at a similar rate as well-represented patients, the researchers note.

“By excluding patients with differing clinical conditions from trials but including them in the population to which drugs can be disseminated, one runs the risk of inadvertently causing injury,” the authors caution.

“To inform the practice of evidence-based medicine in an equitable manner, our findings support a need to both expand clinical trial inclusion criteria and report on clinical trial outcomes by clinical and demographic characteristics,” Dr. Rocque and colleagues conclude.

Charles Shapiro, MD, professor of medicine, hematology, and medical oncology, Icahn School of Medicine at Mount Sinai, New York, is not surprised by the findings of this study.

“We know that clinical trials are too restrictive and include only a selected population largely without comorbidities, but in the real world, people have comorbidities,” Dr. Shapiro, who was not involved in the research, told this news organization.

The study “starkly illustrates” the poorer survival of populations not represented in clinical trials.

“It could be that we need to change clinical trials, maybe ask fewer questions or maybe ask more important questions and loosen the eligibility up, because in the real world, there are people with comorbidities and people who are over 70,” Dr. Shapiro stated.

Are strides being made to change that? “Not really,” Dr. Shapiro said in an interview.

The study was supported by grants from the Robert Wood Johnson Foundation and the American Cancer Society. Dr. Rocque has served as a consultant or advisor for Pfizer; has received research funding from Carevive Systems, Genentech, and Pfizer; and has received travel, accommodations, and expenses from Carevive. Dr. Shapiro has financial relationships with UptoDate, 2nd MD, and Anthenum.

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

Women with early-stage breast cancer who are poorly represented in clinical trials have worse survival than their well-represented peers, according to a real-world analysis.

The study shows that more than half of women with early breast cancer are not well represented in clinical trials because of age, comorbidities, or race, yet they receive therapies based on the results of these trials.

“The most interesting finding is that patients with comorbidities resulting in lab abnormalities that would typically exclude them from receiving medication on a trial are still frequently receiving these medications and have an almost threefold higher mortality,” Gabrielle Rocque, MD, with the division of hematology and oncology, University of Alabama at Birmingham, told this news organization.

“We need to do a deeper dive to better understand what is driving this mortality difference and test specific medications in patients with these conditions to understand the optimal treatment for this population,” Dr. Rocque added.

The study was published Feb. 1 in JCO Oncology Practice.

Many patient groups are not well represented in clinical trials, including patients of color, older patients, and those with comorbidities, and it remains unclear how treatment outcomes may differ among these patients, compared with those who are well represented in trials.

To investigate, Dr. Rocque and colleagues looked at 11,770 women diagnosed with stage I-III breast cancer between 2005 and 2015 in the American Society of Clinical Oncology CancerLinQ database.

White women between 45 and 69 years of age with no comorbid conditions were considered well represented and made up 48% of the cohort.

Non-White women and/or those younger than 45 years or older than 70 were considered under represented and made up 45% of the cohort. The unrepresented group (7%) included women with comorbidities – such as liver disease, renal insufficiency, thrombocytopenia, anemia, or uncontrolled diabetes – or concurrent cancer.

The majority of the women received a high-intensity chemotherapy regimen, including 58% of unrepresented, 66% of underrepresented, and 63% of well-represented patients.

Compared with well-represented women, unrepresented women had a higher risk of death at 5 years (adjusted hazard ratio, 2.71; 95% confidence interval, 2.08-3.52).

Overall, the team found no significant increase in the risk of death at 5 years in underrepresented vs. well-represented women (aHR, 1.19; 95% CI, 0.98-1.45). However, that risk varied with age. Among underrepresented women, those aged 70 and older had more than a twofold higher risk of 5-year mortality (aHR, 2.21), while those younger than 45 had a lower risk of 5-year mortality (aHR, 0.63), compared with those aged 45-69 years.

For three cancer subtypes, unrepresented patients had a greater than twofold higher risk of 5-year mortality, compared with well-represented patients (aHR, 2.50 for HER2-positive disease; aHR, 2.54 for HR-positive/HER2-negative disease; and aHR, 2.75 for triple-negative disease).

Underrepresented patients with HR-positive/HER2-negative disease had a 38% increased risk of 5-year mortality, compared with their well-represented peers (aHR, 1.38). However, there were no significant differences in 5-year mortality for underrepresented vs. well-represented patients with HER2-positive or triple-negative subtypes.
 

Risky business?

This analysis shows that unrepresented populations receive common treatment regimens at a similar rate as well-represented patients, the researchers note.

“By excluding patients with differing clinical conditions from trials but including them in the population to which drugs can be disseminated, one runs the risk of inadvertently causing injury,” the authors caution.

“To inform the practice of evidence-based medicine in an equitable manner, our findings support a need to both expand clinical trial inclusion criteria and report on clinical trial outcomes by clinical and demographic characteristics,” Dr. Rocque and colleagues conclude.

Charles Shapiro, MD, professor of medicine, hematology, and medical oncology, Icahn School of Medicine at Mount Sinai, New York, is not surprised by the findings of this study.

“We know that clinical trials are too restrictive and include only a selected population largely without comorbidities, but in the real world, people have comorbidities,” Dr. Shapiro, who was not involved in the research, told this news organization.

The study “starkly illustrates” the poorer survival of populations not represented in clinical trials.

“It could be that we need to change clinical trials, maybe ask fewer questions or maybe ask more important questions and loosen the eligibility up, because in the real world, there are people with comorbidities and people who are over 70,” Dr. Shapiro stated.

Are strides being made to change that? “Not really,” Dr. Shapiro said in an interview.

The study was supported by grants from the Robert Wood Johnson Foundation and the American Cancer Society. Dr. Rocque has served as a consultant or advisor for Pfizer; has received research funding from Carevive Systems, Genentech, and Pfizer; and has received travel, accommodations, and expenses from Carevive. Dr. Shapiro has financial relationships with UptoDate, 2nd MD, and Anthenum.

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

Reports based on a press release in October 2021 suggested it, but now the full data tell the story: Early monitoring and treatment of anal high-grade squamous intraepithelial lesions (HSIL) cut risk for anal cancer by 57% in people living with HIV.

“We now show, for the first time, that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” said Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the Anal Neoplasia Clinic at the University of California, San Francisco. “These data should be included in an overall assessment for inclusion of screening for and treating HSIL as standard of care in people living with HIV.”

Dr. Palefsky presented the full results in a special session at the Conference on Retroviruses and Opportunistic Infections, which drew excitement, gratitude, and relief from both researchers and clinicians, who flocked to the session.

But it’s not just people with HIV who will benefit from this research. Dr. Palefsky suggested that the findings should also be considered as guides for other people at high-risk for anal cancer, such as people who are immunocompromised for other reasons, including those with lupus, ulcerative colitis, Crohn’s disease, or cisgender women who have had vulvar or cervical cancer or precancer.

“If we can show efficacy in the most challenging group of all, which are people living with HIV, we think the results can be as good, if not even better, in the other groups at high risk of anal cancer,” Dr. Palefsky said.

But to serve anyone – whether living with HIV or not – infrastructure, algorithms, and workforce training are going be needed to meet the currently unserved people through use of high-resolution anoscopy (HRA) and other screening technology, he said.

Dr. Palefsy and colleagues screened 10,723 people living with HIV being served at 15 clinics nationwide. More than half, 52.2%, had anal HSIL – 53.3% of the cisgender men living with HIV in the trial, 45.8% of the cis women living with HIV, and a full 62.5% of transgender participants.

Those 4,446 participants were split evenly between the treatment arm and the control arm. Those in the treatment arm received treatment for HSIL on their first study visit via one of five options: hyfrecation, office-based electrocautery ablation, infrared coagulation, topical 5-fluorouracil cream, or topical imiquimod. Then, every 6 months after that, they came in for HRA, blood tests, anal Pap smears, and biopsies to check for any lingering or new HSIL. If clinicians found such cells, they received treatment again. If biopsies still showed HSIL and clinician and participant were worried about cancer, they could come in as frequently as every 3 months and receive treatment each time.

The active-monitoring control group still received an anal Pap smear, blood tests, biopsy, and HRA every 6 months – a level of care that is currently not mandated anywhere for people living with HIV, Dr. Palefsky said in an interview. They were also able to come in for more frequent monitoring (every 3 months) if clinicians were worried about cancer.

“Those in both arms would have been getting more attention than if they had not participated in the study,” he said.

In addition, during screening, researchers found that cancer was already present in 17 other people, who skipped the study to go right to treatment.

Participants reflected the demographics of the HIV epidemic in the United States. They were older (median age, 51 years), mostly gay (78%), and cisgender male (80%). Close to half, 42%, were Black, and 16% were Latinx. In addition, cisgender women made up 16% of the participants and transgender people, and nonbinary individuals accounted for more than 3% of the participants. In addition, one in three smoked.

The vast majority of participants had well-controlled HIV and healthy immune systems, though half in each arm had a history of AIDS, defined as lowest-ever CD4 immune cell counts below 200. Today, more than 80% of participants had undetectable viral loads, defined as a viral load less than 50 copies/mL, and another 7% had HIV viral loads below 200. In total, 9.3% in the treatment arm and 10.9% in the control arm had HIV viral loads higher than that. At time of enrollment, CD4 counts were above 600 in each group, indicating healthy immune systems.

Although all participants were there because they had anal HSIL, more than 1 in 10 – 13% – had abnormal cells so extensive that they covered more than half of the anal canal or the perianal region.

Once everyone was enrolled, researchers began monitoring and treatment, looking specifically for 31 cases of cancer – a number the team had determined that they’d need in order to draw any conclusions. Dr. Palefsky didn’t have to wait long. They were still trying to enroll the last 1,000 participants to have the power necessary to reach that number when the cancer diagnoses came in.

Dr. Palefsky told this news organization that the reason for that is unclear. It could be that some of those cases would have resolved on their own, and so the swiftness with which they reached the required number of cancer cases belies their seriousness. It could also be that the particular people who enrolled in this trial were engaging in behaviors that put them at even higher risk for anal cancer than the population of people living with HIV in the United States.

Or it could be that symptom-based screening is missing a lot of cancers that currently go untreated.

“So perhaps we will be seeing an increase in anal cancer reported in the future compared to the currently reported rates,” he said. “We don’t really know.”

Regardless of the reason for the speed to cases of cancer, the results were definitive: Nine participants were diagnosed with invasive anal cancer in the treatment arm, while 21 were diagnosed with invasive anal cancer in the control arm. That’s a 57% reduction in cancer occurrence between the arms. Or, to put it another way, the rate of anal cancer among people in the treatment arm was 173 per 100,000 people-years. In the active monitoring arm, it was 402 per 100,000 person-years. For context, the overall rate of anal cancer among people living with HIV is 50 per 100,000 person-years. The rate in the general U.S. population is 8 per 100,000 people-years.

The experimental treatment was such a definitive success that the investigators stopped the trial and shifted all participants in the control arm to treatment.
 

‘We have to build’

Before Dr. Palefsky was even done presenting the data, clinicians, people living with HIV, and experts at the session were already brainstorming as to how to get these results into practice.

“These data are what we have long needed to fuel some action on this important problem, including medical cost reimbursement through insurance and increasing the number of persons trained and capable in anal cancer screening,” John Brooks, MD, head of the epidemiology research team at the Centers for Disease Control and Prevention’s division of HIV/AIDS prevention, wrote in the virtual chat.

Jeff Taylor, a member of the ANCHOR advisory board and a person living with HIV who participated in one of the first azidothymidine trials in the late 1980s, responded quickly.

“What kind of advocacy from researchers, HIV clinicians and [people living with HIV] is needed to get this on treatment guidelines, HRA providers trained and certified, and payors to cover this so [people living with HIV] actually have access to lifesaving screening and [treatment]?” Mr. Taylor asked.

It’s a serious challenge. David Malebranche, MD, an Atlanta-based internal medicine physician who specializes in sexual health and HIV, commented in an interview. When he saw the initial press release last year on the ANCHOR findings, his first reaction was: “Thank god. We finally have some data to show what we’ve been trying to get people to do” all along.

But then he wondered, who is going to perform these tests? It’s a fair question. Currently, the wait for an HRA is 6-12 months in many parts of the country. And Dr. Malebranche can’t imagine this being added to his already full plate as a primary care provider.

“If you tell a primary care provider now that they have to do a rectal Pap smear, that’s going to be a problem while you’re also asking them to screen each patient for depression, anxiety, domestic abuse, intimate partner violence, all the healthcare maintenance and all the other screening tests – and then you deal with not only the urgent complaint but then all the complex medical issues on top of that – in a 15-minute or 10-minute visit,” he said.

Now that we have these data, he said, “we have to build.”

Dr. Palefsky agreed. Very few centers have enough people skilled at performing HRAs to meet the current demand, and it’s not realistic to expect clinicians to perform an HRA every 6 months like the study team did. There need to be algorithms put in place to help practitioners figure out who among their patients living with HIV could benefit from this increased screening, as well as biomarkers to identify HSIL progression and regression without the use of HRA, Dr. Palefsky told attendees. And more clinicians need to be recruited and trained to read HRAs, which can be difficult for the untrained eye to decipher.

Dr. Malebranche added another, more fundamental thing that needs to be built. Dr. Malebranche has worked in HIV clinics where the majority of his patients qualify for insurance under the Ryan White Program and get their medications through the AIDS Drug Assistance Program. While Ryan White programs can provide critical wraparound care, Dr. Malebranche has had to refer out for something like an HRA or cancer treatment. But the people who only access care through such programs may not have coverage with the clinics that perform HRA or that treat cancer. And that’s if they can even find someone to see them.

“If I live in a state like Georgia, which doesn’t have Medicaid expansion and we have people who are uninsured, where do you send them?” Dr. Malebranche asked. “This isn’t theoretical. I ran into this problem when I was working at the AIDS Healthcare Foundation last year. ... This is a call for infrastructure.”

The study was funded by the National Cancer Institute. Dr. Brooks reported no relevant financial relationships. Dr. Palefsky has received consultant fees from Merck, Vir Biotechnology, Virion Therapeutics, and Antiva Bioscience, as well as speaker fees from Merck. Dr. Malebranche has received consulting and advising fees from ViiV Healthcare.

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

Reports based on a press release in October 2021 suggested it, but now the full data tell the story: Early monitoring and treatment of anal high-grade squamous intraepithelial lesions (HSIL) cut risk for anal cancer by 57% in people living with HIV.

“We now show, for the first time, that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” said Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the Anal Neoplasia Clinic at the University of California, San Francisco. “These data should be included in an overall assessment for inclusion of screening for and treating HSIL as standard of care in people living with HIV.”

Dr. Palefsky presented the full results in a special session at the Conference on Retroviruses and Opportunistic Infections, which drew excitement, gratitude, and relief from both researchers and clinicians, who flocked to the session.

But it’s not just people with HIV who will benefit from this research. Dr. Palefsky suggested that the findings should also be considered as guides for other people at high-risk for anal cancer, such as people who are immunocompromised for other reasons, including those with lupus, ulcerative colitis, Crohn’s disease, or cisgender women who have had vulvar or cervical cancer or precancer.

“If we can show efficacy in the most challenging group of all, which are people living with HIV, we think the results can be as good, if not even better, in the other groups at high risk of anal cancer,” Dr. Palefsky said.

But to serve anyone – whether living with HIV or not – infrastructure, algorithms, and workforce training are going be needed to meet the currently unserved people through use of high-resolution anoscopy (HRA) and other screening technology, he said.

Dr. Palefsy and colleagues screened 10,723 people living with HIV being served at 15 clinics nationwide. More than half, 52.2%, had anal HSIL – 53.3% of the cisgender men living with HIV in the trial, 45.8% of the cis women living with HIV, and a full 62.5% of transgender participants.

Those 4,446 participants were split evenly between the treatment arm and the control arm. Those in the treatment arm received treatment for HSIL on their first study visit via one of five options: hyfrecation, office-based electrocautery ablation, infrared coagulation, topical 5-fluorouracil cream, or topical imiquimod. Then, every 6 months after that, they came in for HRA, blood tests, anal Pap smears, and biopsies to check for any lingering or new HSIL. If clinicians found such cells, they received treatment again. If biopsies still showed HSIL and clinician and participant were worried about cancer, they could come in as frequently as every 3 months and receive treatment each time.

The active-monitoring control group still received an anal Pap smear, blood tests, biopsy, and HRA every 6 months – a level of care that is currently not mandated anywhere for people living with HIV, Dr. Palefsky said in an interview. They were also able to come in for more frequent monitoring (every 3 months) if clinicians were worried about cancer.

“Those in both arms would have been getting more attention than if they had not participated in the study,” he said.

In addition, during screening, researchers found that cancer was already present in 17 other people, who skipped the study to go right to treatment.

Participants reflected the demographics of the HIV epidemic in the United States. They were older (median age, 51 years), mostly gay (78%), and cisgender male (80%). Close to half, 42%, were Black, and 16% were Latinx. In addition, cisgender women made up 16% of the participants and transgender people, and nonbinary individuals accounted for more than 3% of the participants. In addition, one in three smoked.

The vast majority of participants had well-controlled HIV and healthy immune systems, though half in each arm had a history of AIDS, defined as lowest-ever CD4 immune cell counts below 200. Today, more than 80% of participants had undetectable viral loads, defined as a viral load less than 50 copies/mL, and another 7% had HIV viral loads below 200. In total, 9.3% in the treatment arm and 10.9% in the control arm had HIV viral loads higher than that. At time of enrollment, CD4 counts were above 600 in each group, indicating healthy immune systems.

Although all participants were there because they had anal HSIL, more than 1 in 10 – 13% – had abnormal cells so extensive that they covered more than half of the anal canal or the perianal region.

Once everyone was enrolled, researchers began monitoring and treatment, looking specifically for 31 cases of cancer – a number the team had determined that they’d need in order to draw any conclusions. Dr. Palefsky didn’t have to wait long. They were still trying to enroll the last 1,000 participants to have the power necessary to reach that number when the cancer diagnoses came in.

Dr. Palefsky told this news organization that the reason for that is unclear. It could be that some of those cases would have resolved on their own, and so the swiftness with which they reached the required number of cancer cases belies their seriousness. It could also be that the particular people who enrolled in this trial were engaging in behaviors that put them at even higher risk for anal cancer than the population of people living with HIV in the United States.

Or it could be that symptom-based screening is missing a lot of cancers that currently go untreated.

“So perhaps we will be seeing an increase in anal cancer reported in the future compared to the currently reported rates,” he said. “We don’t really know.”

Regardless of the reason for the speed to cases of cancer, the results were definitive: Nine participants were diagnosed with invasive anal cancer in the treatment arm, while 21 were diagnosed with invasive anal cancer in the control arm. That’s a 57% reduction in cancer occurrence between the arms. Or, to put it another way, the rate of anal cancer among people in the treatment arm was 173 per 100,000 people-years. In the active monitoring arm, it was 402 per 100,000 person-years. For context, the overall rate of anal cancer among people living with HIV is 50 per 100,000 person-years. The rate in the general U.S. population is 8 per 100,000 people-years.

The experimental treatment was such a definitive success that the investigators stopped the trial and shifted all participants in the control arm to treatment.
 

‘We have to build’

Before Dr. Palefsky was even done presenting the data, clinicians, people living with HIV, and experts at the session were already brainstorming as to how to get these results into practice.

“These data are what we have long needed to fuel some action on this important problem, including medical cost reimbursement through insurance and increasing the number of persons trained and capable in anal cancer screening,” John Brooks, MD, head of the epidemiology research team at the Centers for Disease Control and Prevention’s division of HIV/AIDS prevention, wrote in the virtual chat.

Jeff Taylor, a member of the ANCHOR advisory board and a person living with HIV who participated in one of the first azidothymidine trials in the late 1980s, responded quickly.

“What kind of advocacy from researchers, HIV clinicians and [people living with HIV] is needed to get this on treatment guidelines, HRA providers trained and certified, and payors to cover this so [people living with HIV] actually have access to lifesaving screening and [treatment]?” Mr. Taylor asked.

It’s a serious challenge. David Malebranche, MD, an Atlanta-based internal medicine physician who specializes in sexual health and HIV, commented in an interview. When he saw the initial press release last year on the ANCHOR findings, his first reaction was: “Thank god. We finally have some data to show what we’ve been trying to get people to do” all along.

But then he wondered, who is going to perform these tests? It’s a fair question. Currently, the wait for an HRA is 6-12 months in many parts of the country. And Dr. Malebranche can’t imagine this being added to his already full plate as a primary care provider.

“If you tell a primary care provider now that they have to do a rectal Pap smear, that’s going to be a problem while you’re also asking them to screen each patient for depression, anxiety, domestic abuse, intimate partner violence, all the healthcare maintenance and all the other screening tests – and then you deal with not only the urgent complaint but then all the complex medical issues on top of that – in a 15-minute or 10-minute visit,” he said.

Now that we have these data, he said, “we have to build.”

Dr. Palefsky agreed. Very few centers have enough people skilled at performing HRAs to meet the current demand, and it’s not realistic to expect clinicians to perform an HRA every 6 months like the study team did. There need to be algorithms put in place to help practitioners figure out who among their patients living with HIV could benefit from this increased screening, as well as biomarkers to identify HSIL progression and regression without the use of HRA, Dr. Palefsky told attendees. And more clinicians need to be recruited and trained to read HRAs, which can be difficult for the untrained eye to decipher.

Dr. Malebranche added another, more fundamental thing that needs to be built. Dr. Malebranche has worked in HIV clinics where the majority of his patients qualify for insurance under the Ryan White Program and get their medications through the AIDS Drug Assistance Program. While Ryan White programs can provide critical wraparound care, Dr. Malebranche has had to refer out for something like an HRA or cancer treatment. But the people who only access care through such programs may not have coverage with the clinics that perform HRA or that treat cancer. And that’s if they can even find someone to see them.

“If I live in a state like Georgia, which doesn’t have Medicaid expansion and we have people who are uninsured, where do you send them?” Dr. Malebranche asked. “This isn’t theoretical. I ran into this problem when I was working at the AIDS Healthcare Foundation last year. ... This is a call for infrastructure.”

The study was funded by the National Cancer Institute. Dr. Brooks reported no relevant financial relationships. Dr. Palefsky has received consultant fees from Merck, Vir Biotechnology, Virion Therapeutics, and Antiva Bioscience, as well as speaker fees from Merck. Dr. Malebranche has received consulting and advising fees from ViiV Healthcare.

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

Reports based on a press release in October 2021 suggested it, but now the full data tell the story: Early monitoring and treatment of anal high-grade squamous intraepithelial lesions (HSIL) cut risk for anal cancer by 57% in people living with HIV.

“We now show, for the first time, that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” said Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the Anal Neoplasia Clinic at the University of California, San Francisco. “These data should be included in an overall assessment for inclusion of screening for and treating HSIL as standard of care in people living with HIV.”

Dr. Palefsky presented the full results in a special session at the Conference on Retroviruses and Opportunistic Infections, which drew excitement, gratitude, and relief from both researchers and clinicians, who flocked to the session.

But it’s not just people with HIV who will benefit from this research. Dr. Palefsky suggested that the findings should also be considered as guides for other people at high-risk for anal cancer, such as people who are immunocompromised for other reasons, including those with lupus, ulcerative colitis, Crohn’s disease, or cisgender women who have had vulvar or cervical cancer or precancer.

“If we can show efficacy in the most challenging group of all, which are people living with HIV, we think the results can be as good, if not even better, in the other groups at high risk of anal cancer,” Dr. Palefsky said.

But to serve anyone – whether living with HIV or not – infrastructure, algorithms, and workforce training are going be needed to meet the currently unserved people through use of high-resolution anoscopy (HRA) and other screening technology, he said.

Dr. Palefsy and colleagues screened 10,723 people living with HIV being served at 15 clinics nationwide. More than half, 52.2%, had anal HSIL – 53.3% of the cisgender men living with HIV in the trial, 45.8% of the cis women living with HIV, and a full 62.5% of transgender participants.

Those 4,446 participants were split evenly between the treatment arm and the control arm. Those in the treatment arm received treatment for HSIL on their first study visit via one of five options: hyfrecation, office-based electrocautery ablation, infrared coagulation, topical 5-fluorouracil cream, or topical imiquimod. Then, every 6 months after that, they came in for HRA, blood tests, anal Pap smears, and biopsies to check for any lingering or new HSIL. If clinicians found such cells, they received treatment again. If biopsies still showed HSIL and clinician and participant were worried about cancer, they could come in as frequently as every 3 months and receive treatment each time.

The active-monitoring control group still received an anal Pap smear, blood tests, biopsy, and HRA every 6 months – a level of care that is currently not mandated anywhere for people living with HIV, Dr. Palefsky said in an interview. They were also able to come in for more frequent monitoring (every 3 months) if clinicians were worried about cancer.

“Those in both arms would have been getting more attention than if they had not participated in the study,” he said.

In addition, during screening, researchers found that cancer was already present in 17 other people, who skipped the study to go right to treatment.

Participants reflected the demographics of the HIV epidemic in the United States. They were older (median age, 51 years), mostly gay (78%), and cisgender male (80%). Close to half, 42%, were Black, and 16% were Latinx. In addition, cisgender women made up 16% of the participants and transgender people, and nonbinary individuals accounted for more than 3% of the participants. In addition, one in three smoked.

The vast majority of participants had well-controlled HIV and healthy immune systems, though half in each arm had a history of AIDS, defined as lowest-ever CD4 immune cell counts below 200. Today, more than 80% of participants had undetectable viral loads, defined as a viral load less than 50 copies/mL, and another 7% had HIV viral loads below 200. In total, 9.3% in the treatment arm and 10.9% in the control arm had HIV viral loads higher than that. At time of enrollment, CD4 counts were above 600 in each group, indicating healthy immune systems.

Although all participants were there because they had anal HSIL, more than 1 in 10 – 13% – had abnormal cells so extensive that they covered more than half of the anal canal or the perianal region.

Once everyone was enrolled, researchers began monitoring and treatment, looking specifically for 31 cases of cancer – a number the team had determined that they’d need in order to draw any conclusions. Dr. Palefsky didn’t have to wait long. They were still trying to enroll the last 1,000 participants to have the power necessary to reach that number when the cancer diagnoses came in.

Dr. Palefsky told this news organization that the reason for that is unclear. It could be that some of those cases would have resolved on their own, and so the swiftness with which they reached the required number of cancer cases belies their seriousness. It could also be that the particular people who enrolled in this trial were engaging in behaviors that put them at even higher risk for anal cancer than the population of people living with HIV in the United States.

Or it could be that symptom-based screening is missing a lot of cancers that currently go untreated.

“So perhaps we will be seeing an increase in anal cancer reported in the future compared to the currently reported rates,” he said. “We don’t really know.”

Regardless of the reason for the speed to cases of cancer, the results were definitive: Nine participants were diagnosed with invasive anal cancer in the treatment arm, while 21 were diagnosed with invasive anal cancer in the control arm. That’s a 57% reduction in cancer occurrence between the arms. Or, to put it another way, the rate of anal cancer among people in the treatment arm was 173 per 100,000 people-years. In the active monitoring arm, it was 402 per 100,000 person-years. For context, the overall rate of anal cancer among people living with HIV is 50 per 100,000 person-years. The rate in the general U.S. population is 8 per 100,000 people-years.

The experimental treatment was such a definitive success that the investigators stopped the trial and shifted all participants in the control arm to treatment.
 

‘We have to build’

Before Dr. Palefsky was even done presenting the data, clinicians, people living with HIV, and experts at the session were already brainstorming as to how to get these results into practice.

“These data are what we have long needed to fuel some action on this important problem, including medical cost reimbursement through insurance and increasing the number of persons trained and capable in anal cancer screening,” John Brooks, MD, head of the epidemiology research team at the Centers for Disease Control and Prevention’s division of HIV/AIDS prevention, wrote in the virtual chat.

Jeff Taylor, a member of the ANCHOR advisory board and a person living with HIV who participated in one of the first azidothymidine trials in the late 1980s, responded quickly.

“What kind of advocacy from researchers, HIV clinicians and [people living with HIV] is needed to get this on treatment guidelines, HRA providers trained and certified, and payors to cover this so [people living with HIV] actually have access to lifesaving screening and [treatment]?” Mr. Taylor asked.

It’s a serious challenge. David Malebranche, MD, an Atlanta-based internal medicine physician who specializes in sexual health and HIV, commented in an interview. When he saw the initial press release last year on the ANCHOR findings, his first reaction was: “Thank god. We finally have some data to show what we’ve been trying to get people to do” all along.

But then he wondered, who is going to perform these tests? It’s a fair question. Currently, the wait for an HRA is 6-12 months in many parts of the country. And Dr. Malebranche can’t imagine this being added to his already full plate as a primary care provider.

“If you tell a primary care provider now that they have to do a rectal Pap smear, that’s going to be a problem while you’re also asking them to screen each patient for depression, anxiety, domestic abuse, intimate partner violence, all the healthcare maintenance and all the other screening tests – and then you deal with not only the urgent complaint but then all the complex medical issues on top of that – in a 15-minute or 10-minute visit,” he said.

Now that we have these data, he said, “we have to build.”

Dr. Palefsky agreed. Very few centers have enough people skilled at performing HRAs to meet the current demand, and it’s not realistic to expect clinicians to perform an HRA every 6 months like the study team did. There need to be algorithms put in place to help practitioners figure out who among their patients living with HIV could benefit from this increased screening, as well as biomarkers to identify HSIL progression and regression without the use of HRA, Dr. Palefsky told attendees. And more clinicians need to be recruited and trained to read HRAs, which can be difficult for the untrained eye to decipher.

Dr. Malebranche added another, more fundamental thing that needs to be built. Dr. Malebranche has worked in HIV clinics where the majority of his patients qualify for insurance under the Ryan White Program and get their medications through the AIDS Drug Assistance Program. While Ryan White programs can provide critical wraparound care, Dr. Malebranche has had to refer out for something like an HRA or cancer treatment. But the people who only access care through such programs may not have coverage with the clinics that perform HRA or that treat cancer. And that’s if they can even find someone to see them.

“If I live in a state like Georgia, which doesn’t have Medicaid expansion and we have people who are uninsured, where do you send them?” Dr. Malebranche asked. “This isn’t theoretical. I ran into this problem when I was working at the AIDS Healthcare Foundation last year. ... This is a call for infrastructure.”

The study was funded by the National Cancer Institute. Dr. Brooks reported no relevant financial relationships. Dr. Palefsky has received consultant fees from Merck, Vir Biotechnology, Virion Therapeutics, and Antiva Bioscience, as well as speaker fees from Merck. Dr. Malebranche has received consulting and advising fees from ViiV Healthcare.

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