Susan London

A test that uses machine learning may improve the management of patients with pancreatic cysts, sparing some of them unnecessary surgery, a cohort study suggests.

The test, called CompCyst, integrates clinical, imaging, and biomarker data. It proved more accurate than the current standard of care for correctly determining whether patients should be discharged from follow-up, immediately operated on, or monitored.

Rachel Karchin, PhD, of the Johns Hopkins Whiting School of Engineering in Baltimore, reported these results at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract IA-13).

“Preoperative diagnosis of pancreatic cysts and managing patients who present with a cyst are a clinical conundrum because pancreatic cancer is so deadly, while the decision to surgically resect a cyst is complicated by the danger of the surgery, which has high morbidity and mortality,” Dr. Karchin explained. “The challenge of the diagnostic test is to place patients into one of three groups: those who should be discharged, who should be operated on, and who should be monitored.”

High sensitivity is important for the operate and monitor groups to ensure identification of all patients needing these approaches, whereas higher specificity is important for the discharge group to avoid falsely classifying premalignant cysts, Dr. Karchin said.

She and her colleagues applied machine learning to this classification challenge, using data from 862 patients who had undergone resection of pancreatic cysts at 16 centers in the United States, Europe, and Asia. All patients had a known cyst histopathology, which served as the gold standard, and a known clinical management strategy (discharge, operate, or monitor).

The investigators used a multivariate organization of combinatorial alterations algorithm that integrates clinical features, imaging characteristics, cyst fluid genetics, and serum biomarkers to create classifiers. This algorithm can be trained to maximize sensitivity, maximize specificity, or balance these metrics, Dr. Karchin noted.

The resulting test, CompCyst, was trained using data from 436 of the patients and then validated in the remaining 426 patients.

In the validation cohort, for classifying patients who should be discharged from care, the test had a sensitivity of 46% and a specificity of 100%, according to results reported at the conference and published previously (Sci Transl Med. 2019 Jul 19. doi: 10.1126/scitranslmed.aav4772).

For immediately operating, CompCyst had a sensitivity of 91% and a specificity of 54%. And for monitoring the patient, the test had a sensitivity of 99% and a specificity of 30%.

When CompCyst was compared against the standard of care based on conventional clinical and imaging criteria alone, the former was more accurate. CompCyst correctly identified larger shares of patients who should have been discharged (60% vs. 19%) and who should have been monitored (49% vs. 34%), and the test identified a similar share of patients who should have immediately had an operation (91% vs. 89%).

“The takeaway from this is that standard of care is sending too many patients unnecessarily to surgery,” Dr. Karchin commented. “The CompCyst test, with application of the three classifiers sequentially – discharge, operate, or monitor – could reduce unnecessary surgery by 60% or more based on our calculations.”

“While our study was retrospective, it shows promising results in reducing unnecessary surgeries, compared to current standard of care,” she said, adding that a prospective study is planned next.

“In 10-12 weeks, this CompCyst diagnostic test is going to be available at Johns Hopkins for patients. I’m very excited about that,” Dr. Karchin concluded. “We hope that our study shows the potential of combining clinical, imaging, and genetic features with machine learning to improve clinical judgment about many diseases.”

Dr. Karchin disclosed no conflicts of interest. The study was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, and the National Institutes of Health.

Help your patients understand pancreatitis testing and treatment options, symptoms and complications by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/pancreatitis.

A test that uses machine learning may improve the management of patients with pancreatic cysts, sparing some of them unnecessary surgery, a cohort study suggests.

The test, called CompCyst, integrates clinical, imaging, and biomarker data. It proved more accurate than the current standard of care for correctly determining whether patients should be discharged from follow-up, immediately operated on, or monitored.

Rachel Karchin, PhD, of the Johns Hopkins Whiting School of Engineering in Baltimore, reported these results at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract IA-13).

“Preoperative diagnosis of pancreatic cysts and managing patients who present with a cyst are a clinical conundrum because pancreatic cancer is so deadly, while the decision to surgically resect a cyst is complicated by the danger of the surgery, which has high morbidity and mortality,” Dr. Karchin explained. “The challenge of the diagnostic test is to place patients into one of three groups: those who should be discharged, who should be operated on, and who should be monitored.”

High sensitivity is important for the operate and monitor groups to ensure identification of all patients needing these approaches, whereas higher specificity is important for the discharge group to avoid falsely classifying premalignant cysts, Dr. Karchin said.

She and her colleagues applied machine learning to this classification challenge, using data from 862 patients who had undergone resection of pancreatic cysts at 16 centers in the United States, Europe, and Asia. All patients had a known cyst histopathology, which served as the gold standard, and a known clinical management strategy (discharge, operate, or monitor).

The investigators used a multivariate organization of combinatorial alterations algorithm that integrates clinical features, imaging characteristics, cyst fluid genetics, and serum biomarkers to create classifiers. This algorithm can be trained to maximize sensitivity, maximize specificity, or balance these metrics, Dr. Karchin noted.

The resulting test, CompCyst, was trained using data from 436 of the patients and then validated in the remaining 426 patients.

In the validation cohort, for classifying patients who should be discharged from care, the test had a sensitivity of 46% and a specificity of 100%, according to results reported at the conference and published previously (Sci Transl Med. 2019 Jul 19. doi: 10.1126/scitranslmed.aav4772).

For immediately operating, CompCyst had a sensitivity of 91% and a specificity of 54%. And for monitoring the patient, the test had a sensitivity of 99% and a specificity of 30%.

When CompCyst was compared against the standard of care based on conventional clinical and imaging criteria alone, the former was more accurate. CompCyst correctly identified larger shares of patients who should have been discharged (60% vs. 19%) and who should have been monitored (49% vs. 34%), and the test identified a similar share of patients who should have immediately had an operation (91% vs. 89%).

“The takeaway from this is that standard of care is sending too many patients unnecessarily to surgery,” Dr. Karchin commented. “The CompCyst test, with application of the three classifiers sequentially – discharge, operate, or monitor – could reduce unnecessary surgery by 60% or more based on our calculations.”

“While our study was retrospective, it shows promising results in reducing unnecessary surgeries, compared to current standard of care,” she said, adding that a prospective study is planned next.

“In 10-12 weeks, this CompCyst diagnostic test is going to be available at Johns Hopkins for patients. I’m very excited about that,” Dr. Karchin concluded. “We hope that our study shows the potential of combining clinical, imaging, and genetic features with machine learning to improve clinical judgment about many diseases.”

Dr. Karchin disclosed no conflicts of interest. The study was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, and the National Institutes of Health.

Help your patients understand pancreatitis testing and treatment options, symptoms and complications by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/pancreatitis.

A test that uses machine learning may improve the management of patients with pancreatic cysts, sparing some of them unnecessary surgery, a cohort study suggests.

The test, called CompCyst, integrates clinical, imaging, and biomarker data. It proved more accurate than the current standard of care for correctly determining whether patients should be discharged from follow-up, immediately operated on, or monitored.

Rachel Karchin, PhD, of the Johns Hopkins Whiting School of Engineering in Baltimore, reported these results at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract IA-13).

“Preoperative diagnosis of pancreatic cysts and managing patients who present with a cyst are a clinical conundrum because pancreatic cancer is so deadly, while the decision to surgically resect a cyst is complicated by the danger of the surgery, which has high morbidity and mortality,” Dr. Karchin explained. “The challenge of the diagnostic test is to place patients into one of three groups: those who should be discharged, who should be operated on, and who should be monitored.”

High sensitivity is important for the operate and monitor groups to ensure identification of all patients needing these approaches, whereas higher specificity is important for the discharge group to avoid falsely classifying premalignant cysts, Dr. Karchin said.

She and her colleagues applied machine learning to this classification challenge, using data from 862 patients who had undergone resection of pancreatic cysts at 16 centers in the United States, Europe, and Asia. All patients had a known cyst histopathology, which served as the gold standard, and a known clinical management strategy (discharge, operate, or monitor).

The investigators used a multivariate organization of combinatorial alterations algorithm that integrates clinical features, imaging characteristics, cyst fluid genetics, and serum biomarkers to create classifiers. This algorithm can be trained to maximize sensitivity, maximize specificity, or balance these metrics, Dr. Karchin noted.

The resulting test, CompCyst, was trained using data from 436 of the patients and then validated in the remaining 426 patients.

In the validation cohort, for classifying patients who should be discharged from care, the test had a sensitivity of 46% and a specificity of 100%, according to results reported at the conference and published previously (Sci Transl Med. 2019 Jul 19. doi: 10.1126/scitranslmed.aav4772).

For immediately operating, CompCyst had a sensitivity of 91% and a specificity of 54%. And for monitoring the patient, the test had a sensitivity of 99% and a specificity of 30%.

When CompCyst was compared against the standard of care based on conventional clinical and imaging criteria alone, the former was more accurate. CompCyst correctly identified larger shares of patients who should have been discharged (60% vs. 19%) and who should have been monitored (49% vs. 34%), and the test identified a similar share of patients who should have immediately had an operation (91% vs. 89%).

“The takeaway from this is that standard of care is sending too many patients unnecessarily to surgery,” Dr. Karchin commented. “The CompCyst test, with application of the three classifiers sequentially – discharge, operate, or monitor – could reduce unnecessary surgery by 60% or more based on our calculations.”

“While our study was retrospective, it shows promising results in reducing unnecessary surgeries, compared to current standard of care,” she said, adding that a prospective study is planned next.

“In 10-12 weeks, this CompCyst diagnostic test is going to be available at Johns Hopkins for patients. I’m very excited about that,” Dr. Karchin concluded. “We hope that our study shows the potential of combining clinical, imaging, and genetic features with machine learning to improve clinical judgment about many diseases.”

Dr. Karchin disclosed no conflicts of interest. The study was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, and the National Institutes of Health.

Help your patients understand pancreatitis testing and treatment options, symptoms and complications by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/pancreatitis.

A model that crunches data from routine blood tests can accurately identify cancer patients who will develop acute kidney injury (AKI) up to a month before it happens, according to a cohort study.

The algorithm spotted nearly 74% of the patients who went on to develop AKI within 30 days, providing a window for intervention and possibly prevention, according to investigators.

These results were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-11).

“Cancer patients are a high-risk population for AKI due to the nature of their treatment and illness,” said presenter Lauren A. Scanlon, PhD, a data scientist at The Christie NHS Foundation Trust in Huddersfield, England. “AKI causes a huge disruption in treatment and distress for the patient, so it would be amazing if we could, say, predict the AKI before it occurs and prevent it from even happening.”

U.K. health care providers are already using an algorithm to monitor patients’ creatinine levels, comparing new values against historic ones, Dr. Scanlon explained. When that algorithm detects AKI, it issues an alert that triggers implementation of an AKI care bundle, including measures such as fluid monitoring and medication review, within 24 hours.

Taking this concept further, Dr. Scanlon and colleagues developed a random forest model, a type of machine learning algorithm, that incorporates other markers from blood tests routinely obtained for all patients, with the aim of predicting AKI up to 30 days in advance.

“Using routinely collected blood test results will ensure that the model is applicable to all our patients and can be implemented in an automated manner,” Dr. Scanlon noted.

The investigators developed and trained the model using 597,403 blood test results from 48,865 patients undergoing cancer treatment between January 2017 and May 2020.

The model assigns patients to five categories of risk for AKI in the next 30 days: very low, low, medium, high, and very high.

“We wanted the model to output in this way so that it could be used by clinicians alongside their own insight and knowledge on a case-by-case basis,” Dr. Scanlon explained.

The investigators then prospectively validated the model and its risk categories in another 9,913 patients who underwent cancer treatment between June and August 2020.

Using a model threshold of medium risk or higher, the model correctly predicted AKI in 330 (73.8%) of the 447 patients in the validation cohort who ultimately developed AKI.

“This is pretty amazing and shows that this model really is working and can correctly detect these AKIs up to 30 days before they occur, giving a huge window to put in place preventive strategies,” Dr. Scanlon said.

Among the 154 patients in whom the model incorrectly predicted AKI, 9 patients had only a single follow-up blood test and 17 patients did not have any, leaving their actual outcomes unclear.

“Given that AKI detection uses blood tests, an AKI in these patients was never confirmed,” Dr. Scanlon noted. “So this could give a potential benefit of the model that we never intended: It could reduce undiagnosed AKI by flagging those who are at risk.”

“Our next steps are to test the model through a technology clinical trial to see if putting intervention strategies in place does prevent these AKIs from taking place,” Dr. Scanlon concluded. “We are also going to move to ongoing monitoring of the model performance.”

Dr. Scanlon disclosed no conflicts of interest. The study did not receive specific funding.

A model that crunches data from routine blood tests can accurately identify cancer patients who will develop acute kidney injury (AKI) up to a month before it happens, according to a cohort study.

The algorithm spotted nearly 74% of the patients who went on to develop AKI within 30 days, providing a window for intervention and possibly prevention, according to investigators.

These results were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-11).

“Cancer patients are a high-risk population for AKI due to the nature of their treatment and illness,” said presenter Lauren A. Scanlon, PhD, a data scientist at The Christie NHS Foundation Trust in Huddersfield, England. “AKI causes a huge disruption in treatment and distress for the patient, so it would be amazing if we could, say, predict the AKI before it occurs and prevent it from even happening.”

U.K. health care providers are already using an algorithm to monitor patients’ creatinine levels, comparing new values against historic ones, Dr. Scanlon explained. When that algorithm detects AKI, it issues an alert that triggers implementation of an AKI care bundle, including measures such as fluid monitoring and medication review, within 24 hours.

Taking this concept further, Dr. Scanlon and colleagues developed a random forest model, a type of machine learning algorithm, that incorporates other markers from blood tests routinely obtained for all patients, with the aim of predicting AKI up to 30 days in advance.

“Using routinely collected blood test results will ensure that the model is applicable to all our patients and can be implemented in an automated manner,” Dr. Scanlon noted.

The investigators developed and trained the model using 597,403 blood test results from 48,865 patients undergoing cancer treatment between January 2017 and May 2020.

The model assigns patients to five categories of risk for AKI in the next 30 days: very low, low, medium, high, and very high.

“We wanted the model to output in this way so that it could be used by clinicians alongside their own insight and knowledge on a case-by-case basis,” Dr. Scanlon explained.

The investigators then prospectively validated the model and its risk categories in another 9,913 patients who underwent cancer treatment between June and August 2020.

Using a model threshold of medium risk or higher, the model correctly predicted AKI in 330 (73.8%) of the 447 patients in the validation cohort who ultimately developed AKI.

“This is pretty amazing and shows that this model really is working and can correctly detect these AKIs up to 30 days before they occur, giving a huge window to put in place preventive strategies,” Dr. Scanlon said.

Among the 154 patients in whom the model incorrectly predicted AKI, 9 patients had only a single follow-up blood test and 17 patients did not have any, leaving their actual outcomes unclear.

“Given that AKI detection uses blood tests, an AKI in these patients was never confirmed,” Dr. Scanlon noted. “So this could give a potential benefit of the model that we never intended: It could reduce undiagnosed AKI by flagging those who are at risk.”

“Our next steps are to test the model through a technology clinical trial to see if putting intervention strategies in place does prevent these AKIs from taking place,” Dr. Scanlon concluded. “We are also going to move to ongoing monitoring of the model performance.”

Dr. Scanlon disclosed no conflicts of interest. The study did not receive specific funding.

A model that crunches data from routine blood tests can accurately identify cancer patients who will develop acute kidney injury (AKI) up to a month before it happens, according to a cohort study.

The algorithm spotted nearly 74% of the patients who went on to develop AKI within 30 days, providing a window for intervention and possibly prevention, according to investigators.

These results were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-11).

“Cancer patients are a high-risk population for AKI due to the nature of their treatment and illness,” said presenter Lauren A. Scanlon, PhD, a data scientist at The Christie NHS Foundation Trust in Huddersfield, England. “AKI causes a huge disruption in treatment and distress for the patient, so it would be amazing if we could, say, predict the AKI before it occurs and prevent it from even happening.”

U.K. health care providers are already using an algorithm to monitor patients’ creatinine levels, comparing new values against historic ones, Dr. Scanlon explained. When that algorithm detects AKI, it issues an alert that triggers implementation of an AKI care bundle, including measures such as fluid monitoring and medication review, within 24 hours.

Taking this concept further, Dr. Scanlon and colleagues developed a random forest model, a type of machine learning algorithm, that incorporates other markers from blood tests routinely obtained for all patients, with the aim of predicting AKI up to 30 days in advance.

“Using routinely collected blood test results will ensure that the model is applicable to all our patients and can be implemented in an automated manner,” Dr. Scanlon noted.

The investigators developed and trained the model using 597,403 blood test results from 48,865 patients undergoing cancer treatment between January 2017 and May 2020.

The model assigns patients to five categories of risk for AKI in the next 30 days: very low, low, medium, high, and very high.

“We wanted the model to output in this way so that it could be used by clinicians alongside their own insight and knowledge on a case-by-case basis,” Dr. Scanlon explained.

The investigators then prospectively validated the model and its risk categories in another 9,913 patients who underwent cancer treatment between June and August 2020.

Using a model threshold of medium risk or higher, the model correctly predicted AKI in 330 (73.8%) of the 447 patients in the validation cohort who ultimately developed AKI.

“This is pretty amazing and shows that this model really is working and can correctly detect these AKIs up to 30 days before they occur, giving a huge window to put in place preventive strategies,” Dr. Scanlon said.

Among the 154 patients in whom the model incorrectly predicted AKI, 9 patients had only a single follow-up blood test and 17 patients did not have any, leaving their actual outcomes unclear.

“Given that AKI detection uses blood tests, an AKI in these patients was never confirmed,” Dr. Scanlon noted. “So this could give a potential benefit of the model that we never intended: It could reduce undiagnosed AKI by flagging those who are at risk.”

“Our next steps are to test the model through a technology clinical trial to see if putting intervention strategies in place does prevent these AKIs from taking place,” Dr. Scanlon concluded. “We are also going to move to ongoing monitoring of the model performance.”

Dr. Scanlon disclosed no conflicts of interest. The study did not receive specific funding.

A test that uses machine learning may improve the management of patients with pancreatic cysts, sparing some of them unnecessary surgery, a cohort study suggests.

The test, called CompCyst, integrates clinical, imaging, and biomarker data. It proved more accurate than the current standard of care for correctly determining whether patients should be discharged from follow-up, immediately operated on, or monitored.

Rachel Karchin, PhD, of the Johns Hopkins Whiting School of Engineering in Baltimore, reported these results at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract IA-13).

“Preoperative diagnosis of pancreatic cysts and managing patients who present with a cyst are a clinical conundrum because pancreatic cancer is so deadly, while the decision to surgically resect a cyst is complicated by the danger of the surgery, which has high morbidity and mortality,” Dr. Karchin explained. “The challenge of the diagnostic test is to place patients into one of three groups: those who should be discharged, who should be operated on, and who should be monitored.”

High sensitivity is important for the operate and monitor groups to ensure identification of all patients needing these approaches, whereas higher specificity is important for the discharge group to avoid falsely classifying premalignant cysts, Dr. Karchin said.

She and her colleagues applied machine learning to this classification challenge, using data from 862 patients who had undergone resection of pancreatic cysts at 16 centers in the United States, Europe, and Asia. All patients had a known cyst histopathology, which served as the gold standard, and a known clinical management strategy (discharge, operate, or monitor).

The investigators used a multivariate organization of combinatorial alterations algorithm that integrates clinical features, imaging characteristics, cyst fluid genetics, and serum biomarkers to create classifiers. This algorithm can be trained to maximize sensitivity, maximize specificity, or balance these metrics, Dr. Karchin noted.

The resulting test, CompCyst, was trained using data from 436 of the patients and then validated in the remaining 426 patients.

In the validation cohort, for classifying patients who should be discharged from care, the test had a sensitivity of 46% and a specificity of 100%, according to results reported at the conference and published previously (Sci Transl Med. 2019 Jul 19. doi: 10.1126/scitranslmed.aav4772).

For immediately operating, CompCyst had a sensitivity of 91% and a specificity of 54%. And for monitoring the patient, the test had a sensitivity of 99% and a specificity of 30%.

When CompCyst was compared against the standard of care based on conventional clinical and imaging criteria alone, the former was more accurate. CompCyst correctly identified larger shares of patients who should have been discharged (60% vs. 19%) and who should have been monitored (49% vs. 34%), and the test identified a similar share of patients who should have immediately had an operation (91% vs. 89%).

“The takeaway from this is that standard of care is sending too many patients unnecessarily to surgery,” Dr. Karchin commented. “The CompCyst test, with application of the three classifiers sequentially – discharge, operate, or monitor – could reduce unnecessary surgery by 60% or more based on our calculations.”

“While our study was retrospective, it shows promising results in reducing unnecessary surgeries, compared to current standard of care,” she said, adding that a prospective study is planned next.

“In 10-12 weeks, this CompCyst diagnostic test is going to be available at Johns Hopkins for patients. I’m very excited about that,” Dr. Karchin concluded. “We hope that our study shows the potential of combining clinical, imaging, and genetic features with machine learning to improve clinical judgment about many diseases.”

Dr. Karchin disclosed no conflicts of interest. The study was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, and the National Institutes of Health.

A test that uses machine learning may improve the management of patients with pancreatic cysts, sparing some of them unnecessary surgery, a cohort study suggests.

The test, called CompCyst, integrates clinical, imaging, and biomarker data. It proved more accurate than the current standard of care for correctly determining whether patients should be discharged from follow-up, immediately operated on, or monitored.

Rachel Karchin, PhD, of the Johns Hopkins Whiting School of Engineering in Baltimore, reported these results at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract IA-13).

“Preoperative diagnosis of pancreatic cysts and managing patients who present with a cyst are a clinical conundrum because pancreatic cancer is so deadly, while the decision to surgically resect a cyst is complicated by the danger of the surgery, which has high morbidity and mortality,” Dr. Karchin explained. “The challenge of the diagnostic test is to place patients into one of three groups: those who should be discharged, who should be operated on, and who should be monitored.”

High sensitivity is important for the operate and monitor groups to ensure identification of all patients needing these approaches, whereas higher specificity is important for the discharge group to avoid falsely classifying premalignant cysts, Dr. Karchin said.

She and her colleagues applied machine learning to this classification challenge, using data from 862 patients who had undergone resection of pancreatic cysts at 16 centers in the United States, Europe, and Asia. All patients had a known cyst histopathology, which served as the gold standard, and a known clinical management strategy (discharge, operate, or monitor).

The investigators used a multivariate organization of combinatorial alterations algorithm that integrates clinical features, imaging characteristics, cyst fluid genetics, and serum biomarkers to create classifiers. This algorithm can be trained to maximize sensitivity, maximize specificity, or balance these metrics, Dr. Karchin noted.

The resulting test, CompCyst, was trained using data from 436 of the patients and then validated in the remaining 426 patients.

In the validation cohort, for classifying patients who should be discharged from care, the test had a sensitivity of 46% and a specificity of 100%, according to results reported at the conference and published previously (Sci Transl Med. 2019 Jul 19. doi: 10.1126/scitranslmed.aav4772).

For immediately operating, CompCyst had a sensitivity of 91% and a specificity of 54%. And for monitoring the patient, the test had a sensitivity of 99% and a specificity of 30%.

When CompCyst was compared against the standard of care based on conventional clinical and imaging criteria alone, the former was more accurate. CompCyst correctly identified larger shares of patients who should have been discharged (60% vs. 19%) and who should have been monitored (49% vs. 34%), and the test identified a similar share of patients who should have immediately had an operation (91% vs. 89%).

“The takeaway from this is that standard of care is sending too many patients unnecessarily to surgery,” Dr. Karchin commented. “The CompCyst test, with application of the three classifiers sequentially – discharge, operate, or monitor – could reduce unnecessary surgery by 60% or more based on our calculations.”

“While our study was retrospective, it shows promising results in reducing unnecessary surgeries, compared to current standard of care,” she said, adding that a prospective study is planned next.

“In 10-12 weeks, this CompCyst diagnostic test is going to be available at Johns Hopkins for patients. I’m very excited about that,” Dr. Karchin concluded. “We hope that our study shows the potential of combining clinical, imaging, and genetic features with machine learning to improve clinical judgment about many diseases.”

Dr. Karchin disclosed no conflicts of interest. The study was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, and the National Institutes of Health.

A test that uses machine learning may improve the management of patients with pancreatic cysts, sparing some of them unnecessary surgery, a cohort study suggests.

The test, called CompCyst, integrates clinical, imaging, and biomarker data. It proved more accurate than the current standard of care for correctly determining whether patients should be discharged from follow-up, immediately operated on, or monitored.

Rachel Karchin, PhD, of the Johns Hopkins Whiting School of Engineering in Baltimore, reported these results at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract IA-13).

“Preoperative diagnosis of pancreatic cysts and managing patients who present with a cyst are a clinical conundrum because pancreatic cancer is so deadly, while the decision to surgically resect a cyst is complicated by the danger of the surgery, which has high morbidity and mortality,” Dr. Karchin explained. “The challenge of the diagnostic test is to place patients into one of three groups: those who should be discharged, who should be operated on, and who should be monitored.”

High sensitivity is important for the operate and monitor groups to ensure identification of all patients needing these approaches, whereas higher specificity is important for the discharge group to avoid falsely classifying premalignant cysts, Dr. Karchin said.

She and her colleagues applied machine learning to this classification challenge, using data from 862 patients who had undergone resection of pancreatic cysts at 16 centers in the United States, Europe, and Asia. All patients had a known cyst histopathology, which served as the gold standard, and a known clinical management strategy (discharge, operate, or monitor).

The investigators used a multivariate organization of combinatorial alterations algorithm that integrates clinical features, imaging characteristics, cyst fluid genetics, and serum biomarkers to create classifiers. This algorithm can be trained to maximize sensitivity, maximize specificity, or balance these metrics, Dr. Karchin noted.

The resulting test, CompCyst, was trained using data from 436 of the patients and then validated in the remaining 426 patients.

In the validation cohort, for classifying patients who should be discharged from care, the test had a sensitivity of 46% and a specificity of 100%, according to results reported at the conference and published previously (Sci Transl Med. 2019 Jul 19. doi: 10.1126/scitranslmed.aav4772).

For immediately operating, CompCyst had a sensitivity of 91% and a specificity of 54%. And for monitoring the patient, the test had a sensitivity of 99% and a specificity of 30%.

When CompCyst was compared against the standard of care based on conventional clinical and imaging criteria alone, the former was more accurate. CompCyst correctly identified larger shares of patients who should have been discharged (60% vs. 19%) and who should have been monitored (49% vs. 34%), and the test identified a similar share of patients who should have immediately had an operation (91% vs. 89%).

“The takeaway from this is that standard of care is sending too many patients unnecessarily to surgery,” Dr. Karchin commented. “The CompCyst test, with application of the three classifiers sequentially – discharge, operate, or monitor – could reduce unnecessary surgery by 60% or more based on our calculations.”

“While our study was retrospective, it shows promising results in reducing unnecessary surgeries, compared to current standard of care,” she said, adding that a prospective study is planned next.

“In 10-12 weeks, this CompCyst diagnostic test is going to be available at Johns Hopkins for patients. I’m very excited about that,” Dr. Karchin concluded. “We hope that our study shows the potential of combining clinical, imaging, and genetic features with machine learning to improve clinical judgment about many diseases.”

Dr. Karchin disclosed no conflicts of interest. The study was supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Virginia and D.K. Ludwig Fund for Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, the Michael Rolfe Pancreatic Cancer Research Foundation, the Benjamin Baker Scholarship, and the National Institutes of Health.

The molecular biomarkers of advanced non–small cell lung cancer (NSCLC) – and hence the best treatment option – may soon be identified in real time from scans, thanks to a new decision support tool that uses artificial intelligence (AI).

Researchers developed deep learning models that could accurately predict a patient’s PD-L1 and EGFR mutation status without the need for a biopsy. If these models are validated in prospective trials, they could guide treatment decisions in patients with NSCLC, according to the researchers.

Wei Mu, PhD, of Moffitt Cancer Center and Research Institute in Tampa, Fla., described this research at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-03).
 

Rationale

Guidelines from the National Comprehensive Cancer Network (NCCN) endorse tailored treatment for patients with NSCLC; namely, immune checkpoint inhibitors for those with PD-L1-positive tumors and EGFR tyrosine kinase inhibitors for patients with tumors harboring a mutation in EGFR.

However, the conventional approach to ascertaining tumor status for these biomarkers has disadvantages, Dr. Mu noted.

“Both require biopsy, which may fail due to insufficient quality of the tissue and, particularly for NSCLC, may increase the chance of morbidity,” Dr. Mu said.

In addition, there is room for improvement in the rigor of the biomarker assays, and there can be substantial wait times for results.

To address these issues, Dr. Mu and colleagues explored an AI radiomics approach using PET/CT scans.

“We know that EGFR mutation and positive PD-L1 expression may change the metabolism of the peritumor and intratumor microenvironment,” Dr. Mu explained. “Therefore, we had the hypothesis that they can be captured by the FDG-PET/CT images.”
 

Results

The investigators used FDG-PET/CT images from 837 patients with advanced NSCLC treated at four institutions. The team developed AI deep learning models that generated one score for PD-L1 positivity and another score for presence of an EGFR mutation, as well as an associated algorithm that would direct patients to the appropriate treatments depending on the scores.

Results for the PD-L1 deep learning score showed good accuracy in predicting positivity for this ligand, with an area under the curve of 0.89 in the training cohort, 0.84 in the validation cohort, and 0.82 in an external test cohort, Dr. Mu reported. All exceeded the corresponding areas under the curve for maximal standardized uptake values.

Moreover, the score was prognostic and statistically indistinguishable from PD-L1 status determined by immunohistochemistry in predicting progression-free survival.

Similarly, the EGFR deep learning score showed good accuracy in predicting mutational status, with an area under the curve of 0.86 in the training cohort, 0.83 in the validation cohort, and 0.81 in an external test cohort. It outperformed a clinical score based on sex, smoking status, tumor histology, and maximal standardized uptake value in each cohort.

The EGFR deep learning score was prognostic and statistically indistinguishable from EGFR mutational status determined by polymerase chain reaction in predicting progression-free survival.

The models showed good stability when size of the input region of interest was varied, and when different radiologists delineated the region of interest, with an intraclass correlation coefficient of 0.91.

“We developed deep learning models to predict PD-L1 status and EGFR mutation with high accuracy. Using the generated deep learning scores, we obtained a noninvasive treatment decision support tool, which may be useful as a clinical decision support tool pending validation of its clinical utility in a large prospective trial,” Dr. Mu summarized. “Using our tool, NSCLC patients could be directly offered a treatment decision without the need of biopsy.”

“In the future, we will perform a prospective observational trial to compare the results of our noninvasive treatment decision tool with molecular biomarker–based NCCN guidelines,” she said.

The investigators plan to add ALK rearrangement status and prediction of serious adverse events and cachexia to the decision support tool.

Dr. Mu disclosed no conflicts of interest. The study did not have specific funding.

The molecular biomarkers of advanced non–small cell lung cancer (NSCLC) – and hence the best treatment option – may soon be identified in real time from scans, thanks to a new decision support tool that uses artificial intelligence (AI).

Researchers developed deep learning models that could accurately predict a patient’s PD-L1 and EGFR mutation status without the need for a biopsy. If these models are validated in prospective trials, they could guide treatment decisions in patients with NSCLC, according to the researchers.

Wei Mu, PhD, of Moffitt Cancer Center and Research Institute in Tampa, Fla., described this research at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-03).
 

Rationale

Guidelines from the National Comprehensive Cancer Network (NCCN) endorse tailored treatment for patients with NSCLC; namely, immune checkpoint inhibitors for those with PD-L1-positive tumors and EGFR tyrosine kinase inhibitors for patients with tumors harboring a mutation in EGFR.

However, the conventional approach to ascertaining tumor status for these biomarkers has disadvantages, Dr. Mu noted.

“Both require biopsy, which may fail due to insufficient quality of the tissue and, particularly for NSCLC, may increase the chance of morbidity,” Dr. Mu said.

In addition, there is room for improvement in the rigor of the biomarker assays, and there can be substantial wait times for results.

To address these issues, Dr. Mu and colleagues explored an AI radiomics approach using PET/CT scans.

“We know that EGFR mutation and positive PD-L1 expression may change the metabolism of the peritumor and intratumor microenvironment,” Dr. Mu explained. “Therefore, we had the hypothesis that they can be captured by the FDG-PET/CT images.”
 

Results

The investigators used FDG-PET/CT images from 837 patients with advanced NSCLC treated at four institutions. The team developed AI deep learning models that generated one score for PD-L1 positivity and another score for presence of an EGFR mutation, as well as an associated algorithm that would direct patients to the appropriate treatments depending on the scores.

Results for the PD-L1 deep learning score showed good accuracy in predicting positivity for this ligand, with an area under the curve of 0.89 in the training cohort, 0.84 in the validation cohort, and 0.82 in an external test cohort, Dr. Mu reported. All exceeded the corresponding areas under the curve for maximal standardized uptake values.

Moreover, the score was prognostic and statistically indistinguishable from PD-L1 status determined by immunohistochemistry in predicting progression-free survival.

Similarly, the EGFR deep learning score showed good accuracy in predicting mutational status, with an area under the curve of 0.86 in the training cohort, 0.83 in the validation cohort, and 0.81 in an external test cohort. It outperformed a clinical score based on sex, smoking status, tumor histology, and maximal standardized uptake value in each cohort.

The EGFR deep learning score was prognostic and statistically indistinguishable from EGFR mutational status determined by polymerase chain reaction in predicting progression-free survival.

The models showed good stability when size of the input region of interest was varied, and when different radiologists delineated the region of interest, with an intraclass correlation coefficient of 0.91.

“We developed deep learning models to predict PD-L1 status and EGFR mutation with high accuracy. Using the generated deep learning scores, we obtained a noninvasive treatment decision support tool, which may be useful as a clinical decision support tool pending validation of its clinical utility in a large prospective trial,” Dr. Mu summarized. “Using our tool, NSCLC patients could be directly offered a treatment decision without the need of biopsy.”

“In the future, we will perform a prospective observational trial to compare the results of our noninvasive treatment decision tool with molecular biomarker–based NCCN guidelines,” she said.

The investigators plan to add ALK rearrangement status and prediction of serious adverse events and cachexia to the decision support tool.

Dr. Mu disclosed no conflicts of interest. The study did not have specific funding.

The molecular biomarkers of advanced non–small cell lung cancer (NSCLC) – and hence the best treatment option – may soon be identified in real time from scans, thanks to a new decision support tool that uses artificial intelligence (AI).

Researchers developed deep learning models that could accurately predict a patient’s PD-L1 and EGFR mutation status without the need for a biopsy. If these models are validated in prospective trials, they could guide treatment decisions in patients with NSCLC, according to the researchers.

Wei Mu, PhD, of Moffitt Cancer Center and Research Institute in Tampa, Fla., described this research at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-03).
 

Rationale

Guidelines from the National Comprehensive Cancer Network (NCCN) endorse tailored treatment for patients with NSCLC; namely, immune checkpoint inhibitors for those with PD-L1-positive tumors and EGFR tyrosine kinase inhibitors for patients with tumors harboring a mutation in EGFR.

However, the conventional approach to ascertaining tumor status for these biomarkers has disadvantages, Dr. Mu noted.

“Both require biopsy, which may fail due to insufficient quality of the tissue and, particularly for NSCLC, may increase the chance of morbidity,” Dr. Mu said.

In addition, there is room for improvement in the rigor of the biomarker assays, and there can be substantial wait times for results.

To address these issues, Dr. Mu and colleagues explored an AI radiomics approach using PET/CT scans.

“We know that EGFR mutation and positive PD-L1 expression may change the metabolism of the peritumor and intratumor microenvironment,” Dr. Mu explained. “Therefore, we had the hypothesis that they can be captured by the FDG-PET/CT images.”
 

Results

The investigators used FDG-PET/CT images from 837 patients with advanced NSCLC treated at four institutions. The team developed AI deep learning models that generated one score for PD-L1 positivity and another score for presence of an EGFR mutation, as well as an associated algorithm that would direct patients to the appropriate treatments depending on the scores.

Results for the PD-L1 deep learning score showed good accuracy in predicting positivity for this ligand, with an area under the curve of 0.89 in the training cohort, 0.84 in the validation cohort, and 0.82 in an external test cohort, Dr. Mu reported. All exceeded the corresponding areas under the curve for maximal standardized uptake values.

Moreover, the score was prognostic and statistically indistinguishable from PD-L1 status determined by immunohistochemistry in predicting progression-free survival.

Similarly, the EGFR deep learning score showed good accuracy in predicting mutational status, with an area under the curve of 0.86 in the training cohort, 0.83 in the validation cohort, and 0.81 in an external test cohort. It outperformed a clinical score based on sex, smoking status, tumor histology, and maximal standardized uptake value in each cohort.

The EGFR deep learning score was prognostic and statistically indistinguishable from EGFR mutational status determined by polymerase chain reaction in predicting progression-free survival.

The models showed good stability when size of the input region of interest was varied, and when different radiologists delineated the region of interest, with an intraclass correlation coefficient of 0.91.

“We developed deep learning models to predict PD-L1 status and EGFR mutation with high accuracy. Using the generated deep learning scores, we obtained a noninvasive treatment decision support tool, which may be useful as a clinical decision support tool pending validation of its clinical utility in a large prospective trial,” Dr. Mu summarized. “Using our tool, NSCLC patients could be directly offered a treatment decision without the need of biopsy.”

“In the future, we will perform a prospective observational trial to compare the results of our noninvasive treatment decision tool with molecular biomarker–based NCCN guidelines,” she said.

The investigators plan to add ALK rearrangement status and prediction of serious adverse events and cachexia to the decision support tool.

Dr. Mu disclosed no conflicts of interest. The study did not have specific funding.

A combination of biomarkers identifies patients with luminal early breast cancer who can safely skip chemotherapy after surgery, results from the ADAPT HR+/HER2– trial suggest.

The findings were reported at the 2020 San Antonio Breast Cancer Symposium.

“In early luminal breast cancer, optimal patient selection for omission of adjuvant chemotherapy, particularly in patients with one to three involved lymph nodes, is still unclear,” noted principal investigator Nadia Harbeck, MD, PhD, of the University of Munich.

Successive trials have used nodal status, genomic risk scores, and response to preoperative therapy to home in on subsets of women for whom this practice is safe.

The ADAPT HR+/HER2– trial is a phase 3 trial that enrolled 5,625 patients with luminal (hormone receptor–positive, HER2-negative) early breast cancer who were candidates for adjuvant chemotherapy based on conventional criteria.

The trial combined a static biomarker – Oncotype Dx recurrence score (RS) in the baseline core biopsy – and a dynamic biomarker – Ki-67 response to a 3-week course of preoperative endocrine therapy – to personalize adjuvant therapy.

At SABCS 2020, Dr. Harbeck reported results for 2,290 patients having zero to three involved lymph nodes: 868 patients with RS 0-11 and 1,422 patients with RS 12-25 who had a response to brief preoperative endocrine therapy (a Ki-67 fraction ≤10% at surgery). All were treated with endocrine therapy alone as adjuvant therapy.
 

Similar outcomes

The median follow-up was 60 months. The 5-year rate of invasive disease–free survival was 93.9% for the group with RS 0-11 and 92.6% for the group with RS 12-25 and a response to the preoperative endocrine therapy.

The study met its primary endpoint, as the lower limit of the 95% confidence interval for the difference between groups of –3.3% fell just within the predefined margin of –3.3% or less for noninferiority (P = .05).

The groups also had similarly “excellent” distant disease–free survival (96.3% for RS 0-11 and 95.6% for RS 12-25; P = .247) and overall survival (98.0% for RS 0-11 and 97.3% for RS 12-25; P = .160), Dr. Harbeck reported.

The similar distant disease–free survival was consistent regardless of whether women were younger or older than 50 years and regardless of whether women had involved nodes or not.

In multivariate analysis, women had greater risk of distant disease–free survival events if they had three positive lymph nodes versus zero to two (hazard ratio, 3.40) or a pathologic T stage of 2-4 versus 0-1 (HR, 2.24), whereas risk fell with increasing baseline progesterone receptor expression (HR, 0.92).

“Neither patient age nor study arm were prognostic factors for patient outcome,” Dr. Harbeck noted.

In stratified analysis, the negative impact of having three positive nodes was seen only in the group with RS 12-25 and response to preoperative endocrine therapy, suggesting this subgroup may not be good candidates for omission of chemotherapy, she said.
 

Applying results to practice

“In luminal early breast cancer, the following patients – irrespective of their age – can safely be treated by endocrine therapy alone: patients with zero to three involved lymph nodes and recurrence score 0-11, and those with limited nodal burden (zero to two lymph nodes), recurrence score 12-25, and endocrine response after short preoperative endocrine therapy,” Dr. Harbeck summarized.

“Oncotype Dx testing can spare chemotherapy for the majority of patients with up to three involved lymph nodes. Dynamic Ki-67 response testing is feasible in clinical routine and complements baseline risk assessment to define patient selection for therapy deescalation or escalation,” she added.

The investigators have used the trial’s data to develop an algorithm for predicting the probability of response to short-course preoperative endocrine therapy that is available free of charge online (www.enrep.info).

“This may support everyday clinical decision-making in luminal early breast cancer; for example, whether to start a short period of preoperative endocrine therapy at all, and whether to rely on adjuvant endocrine therapy alone, but also in times like these, whether it’s safe to delay surgery by putting patients on prolonged preoperative endocrine therapy if surgical resources are scarce,” Dr. Harbeck commented.

Her clinic is now recruiting patients for the ADAPT Cycle trial, which is testing an endocrine-based approach with a CDK4/6 inhibitor versus chemotherapy in patients who are not candidates for adjuvant endocrine therapy alone. Therefore, all eligible patients receive the short course of endocrine therapy up front as the standard.

“But if you don’t have a trial, what are you going to do on Monday morning? Please let your patient know whether her tumor is endocrine responsive by doing this 3-week preoperative endocrine therapy,” Dr. Harbeck recommended. “It’s easy to do, you can schedule your surgeries better, and in patients with up to three lymph nodes, it helps with your decision-making, not just in the postmenopausal patients but also in the premenopausal patients, regarding whether they can forgo chemotherapy.”

Findings in context

More than 75% of ADAPT patients with RS 12-25 had a response to short-course endocrine therapy, noted invited discussant Lajos Pusztai, MD, DPhil, of the Yale Cancer Center in New Haven, Conn.

“This implies that the endocrine challenge is not informative for most patients,” he said, adding that a related question is whether the 25% of patients who did not have a response and were therefore given chemotherapy benefited from that therapy.

Dr. Pusztai cautioned that, among patients in the group with RS 12-25 who had a response to preoperative endocrine therapy, certain subgroups were fairly or very small: those aged 50 years or younger (330 patients) and those with two or three positive nodes (75 and 22 patients, respectively).

And collective findings of the similar but much larger TAILORx trial and RxPONDER trial (also reported at SABCS 2020) do suggest a benefit of chemotherapy in younger women, regardless of the number of positive nodes.

“Selection of [estrogen receptor]–positive patients with zero to three lymph nodes for adjuvant chemotherapy currently should be based on age and baseline recurrence score or a similar validated molecular assay,” Dr. Pusztai recommended. “TAILORx results guide us in regard to the use of the recurrence score in node-negative patients with a recurrence score of less than 26, and the recently presented RxPONDER results provide evidence for the use of recurrence score in patients with one to three positive nodes with a recurrence score in the range of 0-26. Both of these trials showed benefit in younger women from adjuvant chemotherapy.”

The ADAPT trial was sponsored by Roche, Genomic Health/Exact Sciences, Celgene, Bayer, Teva, and Amgen. Dr. Harbeck disclosed relationships with Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Merck, Novartis, Odonate Therapeutics, Pfizer, Pierre Fabre, Roche/Genentech, Samsung, Sandoz, and Seattle Genetics. Dr. Pusztai disclosed relationships with AstraZeneca, Athenex, Almac, Bristol-Myers Squibb, Biotheranostics, Clovis, Daiichi, Eisai, Genentech, H2Bio, H3 Biomedicine, Immunomedics, Merck, Novartis, Pfizer, Pieris, Radius Health, Syndax, and Seattle Genetics,.

A combination of biomarkers identifies patients with luminal early breast cancer who can safely skip chemotherapy after surgery, results from the ADAPT HR+/HER2– trial suggest.

The findings were reported at the 2020 San Antonio Breast Cancer Symposium.

“In early luminal breast cancer, optimal patient selection for omission of adjuvant chemotherapy, particularly in patients with one to three involved lymph nodes, is still unclear,” noted principal investigator Nadia Harbeck, MD, PhD, of the University of Munich.

Successive trials have used nodal status, genomic risk scores, and response to preoperative therapy to home in on subsets of women for whom this practice is safe.

The ADAPT HR+/HER2– trial is a phase 3 trial that enrolled 5,625 patients with luminal (hormone receptor–positive, HER2-negative) early breast cancer who were candidates for adjuvant chemotherapy based on conventional criteria.

The trial combined a static biomarker – Oncotype Dx recurrence score (RS) in the baseline core biopsy – and a dynamic biomarker – Ki-67 response to a 3-week course of preoperative endocrine therapy – to personalize adjuvant therapy.

At SABCS 2020, Dr. Harbeck reported results for 2,290 patients having zero to three involved lymph nodes: 868 patients with RS 0-11 and 1,422 patients with RS 12-25 who had a response to brief preoperative endocrine therapy (a Ki-67 fraction ≤10% at surgery). All were treated with endocrine therapy alone as adjuvant therapy.
 

Similar outcomes

The median follow-up was 60 months. The 5-year rate of invasive disease–free survival was 93.9% for the group with RS 0-11 and 92.6% for the group with RS 12-25 and a response to the preoperative endocrine therapy.

The study met its primary endpoint, as the lower limit of the 95% confidence interval for the difference between groups of –3.3% fell just within the predefined margin of –3.3% or less for noninferiority (P = .05).

The groups also had similarly “excellent” distant disease–free survival (96.3% for RS 0-11 and 95.6% for RS 12-25; P = .247) and overall survival (98.0% for RS 0-11 and 97.3% for RS 12-25; P = .160), Dr. Harbeck reported.

The similar distant disease–free survival was consistent regardless of whether women were younger or older than 50 years and regardless of whether women had involved nodes or not.

In multivariate analysis, women had greater risk of distant disease–free survival events if they had three positive lymph nodes versus zero to two (hazard ratio, 3.40) or a pathologic T stage of 2-4 versus 0-1 (HR, 2.24), whereas risk fell with increasing baseline progesterone receptor expression (HR, 0.92).

“Neither patient age nor study arm were prognostic factors for patient outcome,” Dr. Harbeck noted.

In stratified analysis, the negative impact of having three positive nodes was seen only in the group with RS 12-25 and response to preoperative endocrine therapy, suggesting this subgroup may not be good candidates for omission of chemotherapy, she said.
 

Applying results to practice

“In luminal early breast cancer, the following patients – irrespective of their age – can safely be treated by endocrine therapy alone: patients with zero to three involved lymph nodes and recurrence score 0-11, and those with limited nodal burden (zero to two lymph nodes), recurrence score 12-25, and endocrine response after short preoperative endocrine therapy,” Dr. Harbeck summarized.

“Oncotype Dx testing can spare chemotherapy for the majority of patients with up to three involved lymph nodes. Dynamic Ki-67 response testing is feasible in clinical routine and complements baseline risk assessment to define patient selection for therapy deescalation or escalation,” she added.

The investigators have used the trial’s data to develop an algorithm for predicting the probability of response to short-course preoperative endocrine therapy that is available free of charge online (www.enrep.info).

“This may support everyday clinical decision-making in luminal early breast cancer; for example, whether to start a short period of preoperative endocrine therapy at all, and whether to rely on adjuvant endocrine therapy alone, but also in times like these, whether it’s safe to delay surgery by putting patients on prolonged preoperative endocrine therapy if surgical resources are scarce,” Dr. Harbeck commented.

Her clinic is now recruiting patients for the ADAPT Cycle trial, which is testing an endocrine-based approach with a CDK4/6 inhibitor versus chemotherapy in patients who are not candidates for adjuvant endocrine therapy alone. Therefore, all eligible patients receive the short course of endocrine therapy up front as the standard.

“But if you don’t have a trial, what are you going to do on Monday morning? Please let your patient know whether her tumor is endocrine responsive by doing this 3-week preoperative endocrine therapy,” Dr. Harbeck recommended. “It’s easy to do, you can schedule your surgeries better, and in patients with up to three lymph nodes, it helps with your decision-making, not just in the postmenopausal patients but also in the premenopausal patients, regarding whether they can forgo chemotherapy.”

Findings in context

More than 75% of ADAPT patients with RS 12-25 had a response to short-course endocrine therapy, noted invited discussant Lajos Pusztai, MD, DPhil, of the Yale Cancer Center in New Haven, Conn.

“This implies that the endocrine challenge is not informative for most patients,” he said, adding that a related question is whether the 25% of patients who did not have a response and were therefore given chemotherapy benefited from that therapy.

Dr. Pusztai cautioned that, among patients in the group with RS 12-25 who had a response to preoperative endocrine therapy, certain subgroups were fairly or very small: those aged 50 years or younger (330 patients) and those with two or three positive nodes (75 and 22 patients, respectively).

And collective findings of the similar but much larger TAILORx trial and RxPONDER trial (also reported at SABCS 2020) do suggest a benefit of chemotherapy in younger women, regardless of the number of positive nodes.

“Selection of [estrogen receptor]–positive patients with zero to three lymph nodes for adjuvant chemotherapy currently should be based on age and baseline recurrence score or a similar validated molecular assay,” Dr. Pusztai recommended. “TAILORx results guide us in regard to the use of the recurrence score in node-negative patients with a recurrence score of less than 26, and the recently presented RxPONDER results provide evidence for the use of recurrence score in patients with one to three positive nodes with a recurrence score in the range of 0-26. Both of these trials showed benefit in younger women from adjuvant chemotherapy.”

The ADAPT trial was sponsored by Roche, Genomic Health/Exact Sciences, Celgene, Bayer, Teva, and Amgen. Dr. Harbeck disclosed relationships with Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Merck, Novartis, Odonate Therapeutics, Pfizer, Pierre Fabre, Roche/Genentech, Samsung, Sandoz, and Seattle Genetics. Dr. Pusztai disclosed relationships with AstraZeneca, Athenex, Almac, Bristol-Myers Squibb, Biotheranostics, Clovis, Daiichi, Eisai, Genentech, H2Bio, H3 Biomedicine, Immunomedics, Merck, Novartis, Pfizer, Pieris, Radius Health, Syndax, and Seattle Genetics,.

A combination of biomarkers identifies patients with luminal early breast cancer who can safely skip chemotherapy after surgery, results from the ADAPT HR+/HER2– trial suggest.

The findings were reported at the 2020 San Antonio Breast Cancer Symposium.

“In early luminal breast cancer, optimal patient selection for omission of adjuvant chemotherapy, particularly in patients with one to three involved lymph nodes, is still unclear,” noted principal investigator Nadia Harbeck, MD, PhD, of the University of Munich.

Successive trials have used nodal status, genomic risk scores, and response to preoperative therapy to home in on subsets of women for whom this practice is safe.

The ADAPT HR+/HER2– trial is a phase 3 trial that enrolled 5,625 patients with luminal (hormone receptor–positive, HER2-negative) early breast cancer who were candidates for adjuvant chemotherapy based on conventional criteria.

The trial combined a static biomarker – Oncotype Dx recurrence score (RS) in the baseline core biopsy – and a dynamic biomarker – Ki-67 response to a 3-week course of preoperative endocrine therapy – to personalize adjuvant therapy.

At SABCS 2020, Dr. Harbeck reported results for 2,290 patients having zero to three involved lymph nodes: 868 patients with RS 0-11 and 1,422 patients with RS 12-25 who had a response to brief preoperative endocrine therapy (a Ki-67 fraction ≤10% at surgery). All were treated with endocrine therapy alone as adjuvant therapy.
 

Similar outcomes

The median follow-up was 60 months. The 5-year rate of invasive disease–free survival was 93.9% for the group with RS 0-11 and 92.6% for the group with RS 12-25 and a response to the preoperative endocrine therapy.

The study met its primary endpoint, as the lower limit of the 95% confidence interval for the difference between groups of –3.3% fell just within the predefined margin of –3.3% or less for noninferiority (P = .05).

The groups also had similarly “excellent” distant disease–free survival (96.3% for RS 0-11 and 95.6% for RS 12-25; P = .247) and overall survival (98.0% for RS 0-11 and 97.3% for RS 12-25; P = .160), Dr. Harbeck reported.

The similar distant disease–free survival was consistent regardless of whether women were younger or older than 50 years and regardless of whether women had involved nodes or not.

In multivariate analysis, women had greater risk of distant disease–free survival events if they had three positive lymph nodes versus zero to two (hazard ratio, 3.40) or a pathologic T stage of 2-4 versus 0-1 (HR, 2.24), whereas risk fell with increasing baseline progesterone receptor expression (HR, 0.92).

“Neither patient age nor study arm were prognostic factors for patient outcome,” Dr. Harbeck noted.

In stratified analysis, the negative impact of having three positive nodes was seen only in the group with RS 12-25 and response to preoperative endocrine therapy, suggesting this subgroup may not be good candidates for omission of chemotherapy, she said.
 

Applying results to practice

“In luminal early breast cancer, the following patients – irrespective of their age – can safely be treated by endocrine therapy alone: patients with zero to three involved lymph nodes and recurrence score 0-11, and those with limited nodal burden (zero to two lymph nodes), recurrence score 12-25, and endocrine response after short preoperative endocrine therapy,” Dr. Harbeck summarized.

“Oncotype Dx testing can spare chemotherapy for the majority of patients with up to three involved lymph nodes. Dynamic Ki-67 response testing is feasible in clinical routine and complements baseline risk assessment to define patient selection for therapy deescalation or escalation,” she added.

The investigators have used the trial’s data to develop an algorithm for predicting the probability of response to short-course preoperative endocrine therapy that is available free of charge online (www.enrep.info).

“This may support everyday clinical decision-making in luminal early breast cancer; for example, whether to start a short period of preoperative endocrine therapy at all, and whether to rely on adjuvant endocrine therapy alone, but also in times like these, whether it’s safe to delay surgery by putting patients on prolonged preoperative endocrine therapy if surgical resources are scarce,” Dr. Harbeck commented.

Her clinic is now recruiting patients for the ADAPT Cycle trial, which is testing an endocrine-based approach with a CDK4/6 inhibitor versus chemotherapy in patients who are not candidates for adjuvant endocrine therapy alone. Therefore, all eligible patients receive the short course of endocrine therapy up front as the standard.

“But if you don’t have a trial, what are you going to do on Monday morning? Please let your patient know whether her tumor is endocrine responsive by doing this 3-week preoperative endocrine therapy,” Dr. Harbeck recommended. “It’s easy to do, you can schedule your surgeries better, and in patients with up to three lymph nodes, it helps with your decision-making, not just in the postmenopausal patients but also in the premenopausal patients, regarding whether they can forgo chemotherapy.”

Findings in context

More than 75% of ADAPT patients with RS 12-25 had a response to short-course endocrine therapy, noted invited discussant Lajos Pusztai, MD, DPhil, of the Yale Cancer Center in New Haven, Conn.

“This implies that the endocrine challenge is not informative for most patients,” he said, adding that a related question is whether the 25% of patients who did not have a response and were therefore given chemotherapy benefited from that therapy.

Dr. Pusztai cautioned that, among patients in the group with RS 12-25 who had a response to preoperative endocrine therapy, certain subgroups were fairly or very small: those aged 50 years or younger (330 patients) and those with two or three positive nodes (75 and 22 patients, respectively).

And collective findings of the similar but much larger TAILORx trial and RxPONDER trial (also reported at SABCS 2020) do suggest a benefit of chemotherapy in younger women, regardless of the number of positive nodes.

“Selection of [estrogen receptor]–positive patients with zero to three lymph nodes for adjuvant chemotherapy currently should be based on age and baseline recurrence score or a similar validated molecular assay,” Dr. Pusztai recommended. “TAILORx results guide us in regard to the use of the recurrence score in node-negative patients with a recurrence score of less than 26, and the recently presented RxPONDER results provide evidence for the use of recurrence score in patients with one to three positive nodes with a recurrence score in the range of 0-26. Both of these trials showed benefit in younger women from adjuvant chemotherapy.”

The ADAPT trial was sponsored by Roche, Genomic Health/Exact Sciences, Celgene, Bayer, Teva, and Amgen. Dr. Harbeck disclosed relationships with Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Merck, Novartis, Odonate Therapeutics, Pfizer, Pierre Fabre, Roche/Genentech, Samsung, Sandoz, and Seattle Genetics. Dr. Pusztai disclosed relationships with AstraZeneca, Athenex, Almac, Bristol-Myers Squibb, Biotheranostics, Clovis, Daiichi, Eisai, Genentech, H2Bio, H3 Biomedicine, Immunomedics, Merck, Novartis, Pfizer, Pieris, Radius Health, Syndax, and Seattle Genetics,.

Irradiating the whole pelvis rather than just the prostate reduces the likelihood of recurrence in men with high-risk locally advanced prostate cancer, according to a randomized controlled trial.

Results from the trial, called POP-RT, were reported at the European Society for Radiology and Oncology 2020 Online Congress.

“A question that has been plaguing the radiation oncology community for the last 3 or 4 decades is, ‘Should the pelvic nodes be treated prophylactically in patients with high-risk prostate cancer?’ ” said Vedang Murthy, MD, of Tata Memorial Centre in Mumbai, India, who presented the POP-RT trial at the meeting.

“A lot of effort has gone into trying to answer this question,” he added.

Unfortunately, the question has remained unanswered, as neither the RTOG 9413 trial nor the French GETUG-01 trial showed clear evidence of benefit.

To gain some insight, Dr. Murthy and colleagues conducted the POP-RT trial (NCT02302105). The study’s final analysis included 222 men with locally advanced prostate cancer who had node-negative disease based on MRI and PSMA PET, but had a high risk for occult pelvic nodal involvement (20% or greater according to the Roach formula). The median nodal risk for the trial population was 37.8%.

The men were randomized to daily image-guided intensity-modulated radiotherapy to the prostate (68 Gy in 25 fractions to the gland and seminal vesicles) or to the whole pelvis (the former plus 50 Gy in 25 fractions to the pelvic nodes as a simultaneous integrated boost, including the bilateral common iliac, internal and external iliac, presacral, and obturator node groups). All patients also received at least 2 years of androgen-deprivation therapy (ADT).
 

Efficacy and toxicity

At a median follow-up of 68 months, the 5-year rate of biochemical failure–free survival, the trial’s primary endpoint, was superior with whole-pelvis radiotherapy (WPRT), at 95.0%, relative to prostate-only radiotherapy (PORT), at 81.2% (hazard ratio, 0.23; P < .0001), Dr. Murthy reported.

Disease-free survival was better in the WPRT group than in the PORT group (89.5% vs. 77.2%; HR, 0.40; P = .002), and the same was true for distant metastasis–free survival (95.0% vs. 87.9%; HR, 0.35; P = .01).

Overall survival was 92.5% with WPRT and 90.8% with PORT, a nonsignificant difference (P = .83).

At the time of biochemical failure, disease recurred in the regional pelvic nodes (with or without distant metastases) in just 1 patient in the WPRT group, compared with 15 patients in the PORT group. Recurrences at other sites were similar across the groups.

The WPRT group had a significantly higher rate of late genitourinary toxicity (17.7% vs. 7.5%; P = .03) but not late gastrointestinal toxicity (6.5% vs. 3.8%; P = .4).

There were no grade 4 toxicities, and the groups were similar on patient-reported outcomes.
 

Explaining the results

Several factors may explain why the POP-RT trial was clearly positive for WPRT, whereas the RTOG 9413 and GETUG-01 trials were not, according to Dr. Murthy.

“We had a much higher-risk group,” he elaborated (with 55% of patients having a nodal risk exceeding 35%), and PSMA PET was used in the workup in the large majority of patients, improving diagnostic sensitivity.

In delivering radiation, “we made sure to include the common iliac nodes and to go up to L4 and L5 and the common iliac junction,” Dr. Murthy further noted.

Also, the POP-RT trial had a higher prostate dose (biological equivalent dose of 129.6 Gy), used image-guided intensity-modulated radiotherapy, and administered ADT for much longer than the other trial (2 years vs. 4-8 months).

“Prophylactic radiotherapy in this trial improved biochemical failure–free survival and disease-free survival in high-risk prostate cancer patients. The improvement in outcomes was seen in spite of giving long-term ADT and in spite of doing dose escalation,” Dr. Murthy summarized. “There is no overall survival difference as of yet, but that remains to be seen.”

“Based on these results, it would be fair to say that whole-pelvis radiotherapy should be considered for these patients with high-risk and very-high-risk prostate cancer,” he concluded.
 

Practice-changing findings

“Overall, I’m very impressed with this study,” commented Colleen A. Lawton, MD, of Medical College of Wisconsin, Milwaukee. “The primary endpoint of biochemical failure–free survival is not a great one, but fortunately, the distant metastasis-free survival, a secondary endpoint, was statistically improved also.”

The POP-RT results are not surprising given other lines of evidence, she noted. For example, early results of a trial among postprostatectomy patients (RTOG 0534) suggest a benefit of pelvic lymph node radiation, and findings from studies in other adenocarcinomas, such as breast and rectal, show that treating the lymph nodes improves outcomes.

“I think the data are practice changing. … mostly because there is so much retrospective data suggesting a benefit from lymph node radiotherapy for prostate cancer, especially with adequate doses, but this is the first prospective randomized trial to use proper dosing to the primary and lymph nodes, and adequate ADT,” Dr. Lawton said. “The use of PSMA PET is also important from a selection perspective in identifying patients more likely to have microscopic versus gross lymph node involvement and in follow-up to identify which patients fail in the lymph nodes.”

“I agree with the authors’ conclusions and would definitely recommend lymph node radiotherapy for these high- and very-high-risk patients in addition to the ADT,” she concluded. “The dose to the lymph nodes at 50 Gy in 25 fractions is a bit higher than has been used in all of the RTOG trials (45 Gy in 25 fractions), and I do believe that adequate doses are critical in seeing a benefit to treatment.”

The POP-RT trial was funded by Tata Memorial Centre, the Uro-Oncology Disease Management Group, and the Terry Fox Foundation. Dr. Murthy disclosed no conflicts of interest. Dr. Lawton disclosed that she was a coauthor of the RTOG 9413 trial.

SOURCE: Murthy V et al. ESTRO 2020, Abstract OC-0613.

Irradiating the whole pelvis rather than just the prostate reduces the likelihood of recurrence in men with high-risk locally advanced prostate cancer, according to a randomized controlled trial.

Results from the trial, called POP-RT, were reported at the European Society for Radiology and Oncology 2020 Online Congress.

“A question that has been plaguing the radiation oncology community for the last 3 or 4 decades is, ‘Should the pelvic nodes be treated prophylactically in patients with high-risk prostate cancer?’ ” said Vedang Murthy, MD, of Tata Memorial Centre in Mumbai, India, who presented the POP-RT trial at the meeting.

“A lot of effort has gone into trying to answer this question,” he added.

Unfortunately, the question has remained unanswered, as neither the RTOG 9413 trial nor the French GETUG-01 trial showed clear evidence of benefit.

To gain some insight, Dr. Murthy and colleagues conducted the POP-RT trial (NCT02302105). The study’s final analysis included 222 men with locally advanced prostate cancer who had node-negative disease based on MRI and PSMA PET, but had a high risk for occult pelvic nodal involvement (20% or greater according to the Roach formula). The median nodal risk for the trial population was 37.8%.

The men were randomized to daily image-guided intensity-modulated radiotherapy to the prostate (68 Gy in 25 fractions to the gland and seminal vesicles) or to the whole pelvis (the former plus 50 Gy in 25 fractions to the pelvic nodes as a simultaneous integrated boost, including the bilateral common iliac, internal and external iliac, presacral, and obturator node groups). All patients also received at least 2 years of androgen-deprivation therapy (ADT).
 

Efficacy and toxicity

At a median follow-up of 68 months, the 5-year rate of biochemical failure–free survival, the trial’s primary endpoint, was superior with whole-pelvis radiotherapy (WPRT), at 95.0%, relative to prostate-only radiotherapy (PORT), at 81.2% (hazard ratio, 0.23; P < .0001), Dr. Murthy reported.

Disease-free survival was better in the WPRT group than in the PORT group (89.5% vs. 77.2%; HR, 0.40; P = .002), and the same was true for distant metastasis–free survival (95.0% vs. 87.9%; HR, 0.35; P = .01).

Overall survival was 92.5% with WPRT and 90.8% with PORT, a nonsignificant difference (P = .83).

At the time of biochemical failure, disease recurred in the regional pelvic nodes (with or without distant metastases) in just 1 patient in the WPRT group, compared with 15 patients in the PORT group. Recurrences at other sites were similar across the groups.

The WPRT group had a significantly higher rate of late genitourinary toxicity (17.7% vs. 7.5%; P = .03) but not late gastrointestinal toxicity (6.5% vs. 3.8%; P = .4).

There were no grade 4 toxicities, and the groups were similar on patient-reported outcomes.
 

Explaining the results

Several factors may explain why the POP-RT trial was clearly positive for WPRT, whereas the RTOG 9413 and GETUG-01 trials were not, according to Dr. Murthy.

“We had a much higher-risk group,” he elaborated (with 55% of patients having a nodal risk exceeding 35%), and PSMA PET was used in the workup in the large majority of patients, improving diagnostic sensitivity.

In delivering radiation, “we made sure to include the common iliac nodes and to go up to L4 and L5 and the common iliac junction,” Dr. Murthy further noted.

Also, the POP-RT trial had a higher prostate dose (biological equivalent dose of 129.6 Gy), used image-guided intensity-modulated radiotherapy, and administered ADT for much longer than the other trial (2 years vs. 4-8 months).

“Prophylactic radiotherapy in this trial improved biochemical failure–free survival and disease-free survival in high-risk prostate cancer patients. The improvement in outcomes was seen in spite of giving long-term ADT and in spite of doing dose escalation,” Dr. Murthy summarized. “There is no overall survival difference as of yet, but that remains to be seen.”

“Based on these results, it would be fair to say that whole-pelvis radiotherapy should be considered for these patients with high-risk and very-high-risk prostate cancer,” he concluded.
 

Practice-changing findings

“Overall, I’m very impressed with this study,” commented Colleen A. Lawton, MD, of Medical College of Wisconsin, Milwaukee. “The primary endpoint of biochemical failure–free survival is not a great one, but fortunately, the distant metastasis-free survival, a secondary endpoint, was statistically improved also.”

The POP-RT results are not surprising given other lines of evidence, she noted. For example, early results of a trial among postprostatectomy patients (RTOG 0534) suggest a benefit of pelvic lymph node radiation, and findings from studies in other adenocarcinomas, such as breast and rectal, show that treating the lymph nodes improves outcomes.

“I think the data are practice changing. … mostly because there is so much retrospective data suggesting a benefit from lymph node radiotherapy for prostate cancer, especially with adequate doses, but this is the first prospective randomized trial to use proper dosing to the primary and lymph nodes, and adequate ADT,” Dr. Lawton said. “The use of PSMA PET is also important from a selection perspective in identifying patients more likely to have microscopic versus gross lymph node involvement and in follow-up to identify which patients fail in the lymph nodes.”

“I agree with the authors’ conclusions and would definitely recommend lymph node radiotherapy for these high- and very-high-risk patients in addition to the ADT,” she concluded. “The dose to the lymph nodes at 50 Gy in 25 fractions is a bit higher than has been used in all of the RTOG trials (45 Gy in 25 fractions), and I do believe that adequate doses are critical in seeing a benefit to treatment.”

The POP-RT trial was funded by Tata Memorial Centre, the Uro-Oncology Disease Management Group, and the Terry Fox Foundation. Dr. Murthy disclosed no conflicts of interest. Dr. Lawton disclosed that she was a coauthor of the RTOG 9413 trial.

SOURCE: Murthy V et al. ESTRO 2020, Abstract OC-0613.

Irradiating the whole pelvis rather than just the prostate reduces the likelihood of recurrence in men with high-risk locally advanced prostate cancer, according to a randomized controlled trial.

Results from the trial, called POP-RT, were reported at the European Society for Radiology and Oncology 2020 Online Congress.

“A question that has been plaguing the radiation oncology community for the last 3 or 4 decades is, ‘Should the pelvic nodes be treated prophylactically in patients with high-risk prostate cancer?’ ” said Vedang Murthy, MD, of Tata Memorial Centre in Mumbai, India, who presented the POP-RT trial at the meeting.

“A lot of effort has gone into trying to answer this question,” he added.

Unfortunately, the question has remained unanswered, as neither the RTOG 9413 trial nor the French GETUG-01 trial showed clear evidence of benefit.

To gain some insight, Dr. Murthy and colleagues conducted the POP-RT trial (NCT02302105). The study’s final analysis included 222 men with locally advanced prostate cancer who had node-negative disease based on MRI and PSMA PET, but had a high risk for occult pelvic nodal involvement (20% or greater according to the Roach formula). The median nodal risk for the trial population was 37.8%.

The men were randomized to daily image-guided intensity-modulated radiotherapy to the prostate (68 Gy in 25 fractions to the gland and seminal vesicles) or to the whole pelvis (the former plus 50 Gy in 25 fractions to the pelvic nodes as a simultaneous integrated boost, including the bilateral common iliac, internal and external iliac, presacral, and obturator node groups). All patients also received at least 2 years of androgen-deprivation therapy (ADT).
 

Efficacy and toxicity

At a median follow-up of 68 months, the 5-year rate of biochemical failure–free survival, the trial’s primary endpoint, was superior with whole-pelvis radiotherapy (WPRT), at 95.0%, relative to prostate-only radiotherapy (PORT), at 81.2% (hazard ratio, 0.23; P < .0001), Dr. Murthy reported.

Disease-free survival was better in the WPRT group than in the PORT group (89.5% vs. 77.2%; HR, 0.40; P = .002), and the same was true for distant metastasis–free survival (95.0% vs. 87.9%; HR, 0.35; P = .01).

Overall survival was 92.5% with WPRT and 90.8% with PORT, a nonsignificant difference (P = .83).

At the time of biochemical failure, disease recurred in the regional pelvic nodes (with or without distant metastases) in just 1 patient in the WPRT group, compared with 15 patients in the PORT group. Recurrences at other sites were similar across the groups.

The WPRT group had a significantly higher rate of late genitourinary toxicity (17.7% vs. 7.5%; P = .03) but not late gastrointestinal toxicity (6.5% vs. 3.8%; P = .4).

There were no grade 4 toxicities, and the groups were similar on patient-reported outcomes.
 

Explaining the results

Several factors may explain why the POP-RT trial was clearly positive for WPRT, whereas the RTOG 9413 and GETUG-01 trials were not, according to Dr. Murthy.

“We had a much higher-risk group,” he elaborated (with 55% of patients having a nodal risk exceeding 35%), and PSMA PET was used in the workup in the large majority of patients, improving diagnostic sensitivity.

In delivering radiation, “we made sure to include the common iliac nodes and to go up to L4 and L5 and the common iliac junction,” Dr. Murthy further noted.

Also, the POP-RT trial had a higher prostate dose (biological equivalent dose of 129.6 Gy), used image-guided intensity-modulated radiotherapy, and administered ADT for much longer than the other trial (2 years vs. 4-8 months).

“Prophylactic radiotherapy in this trial improved biochemical failure–free survival and disease-free survival in high-risk prostate cancer patients. The improvement in outcomes was seen in spite of giving long-term ADT and in spite of doing dose escalation,” Dr. Murthy summarized. “There is no overall survival difference as of yet, but that remains to be seen.”

“Based on these results, it would be fair to say that whole-pelvis radiotherapy should be considered for these patients with high-risk and very-high-risk prostate cancer,” he concluded.
 

Practice-changing findings

“Overall, I’m very impressed with this study,” commented Colleen A. Lawton, MD, of Medical College of Wisconsin, Milwaukee. “The primary endpoint of biochemical failure–free survival is not a great one, but fortunately, the distant metastasis-free survival, a secondary endpoint, was statistically improved also.”

The POP-RT results are not surprising given other lines of evidence, she noted. For example, early results of a trial among postprostatectomy patients (RTOG 0534) suggest a benefit of pelvic lymph node radiation, and findings from studies in other adenocarcinomas, such as breast and rectal, show that treating the lymph nodes improves outcomes.

“I think the data are practice changing. … mostly because there is so much retrospective data suggesting a benefit from lymph node radiotherapy for prostate cancer, especially with adequate doses, but this is the first prospective randomized trial to use proper dosing to the primary and lymph nodes, and adequate ADT,” Dr. Lawton said. “The use of PSMA PET is also important from a selection perspective in identifying patients more likely to have microscopic versus gross lymph node involvement and in follow-up to identify which patients fail in the lymph nodes.”

“I agree with the authors’ conclusions and would definitely recommend lymph node radiotherapy for these high- and very-high-risk patients in addition to the ADT,” she concluded. “The dose to the lymph nodes at 50 Gy in 25 fractions is a bit higher than has been used in all of the RTOG trials (45 Gy in 25 fractions), and I do believe that adequate doses are critical in seeing a benefit to treatment.”

The POP-RT trial was funded by Tata Memorial Centre, the Uro-Oncology Disease Management Group, and the Terry Fox Foundation. Dr. Murthy disclosed no conflicts of interest. Dr. Lawton disclosed that she was a coauthor of the RTOG 9413 trial.

SOURCE: Murthy V et al. ESTRO 2020, Abstract OC-0613.

Compared with the standard 3-week regimen, a 1-week hypofractionated regimen of adjuvant whole-breast radiotherapy had similar efficacy and safety at 5 years of follow-up, according to the U.K. FAST-Forward trial.

The trial was designed to compare the standard regimen (40 Gy in 15 fractions over 3 weeks) with a higher-dose hypofractionated regimen (27 Gy in 5 fractions over 5 days) and a lower-dose hypofractionated regimen (26 Gy in 5 fractions over 5 days) in women who had undergone surgery for early invasive breast cancer.

The 5-year rate of ipsilateral breast tumor relapse was similar with all regimens – 2.1% with the 40-Gy regimen, 1.7% with the 27-Gy regimen, and 1.4% with the 26-Gy regimen. The 26-Gy regimen also had similar safety as the 40-Gy regimen.

These results were presented at the European Society for Radiology and Oncology 2020 Online Congress by Joanne S. Haviland, MSc, of the Institute of Cancer Research in London. Results were also published in The Lancet.

Ms. Haviland said that hypofractionated regimens are attractive because of their shorter overall treatment times, which translate to greater convenience and lower treatment costs.

The historic 5-week regimen (50 Gy in 25 fractions) has been replaced by a 3-week regimen (40 Gy in 15 fractions) in the United Kingdom and elsewhere, and ongoing efforts are exploring whether further hypofractionation can be achieved without compromising efficacy and safety.

“The FAST-Forward trial was the next step on from testing hypofractionated schedules evaluated in earlier trials, including the START trials in the early 2000s and the FAST trial, which published its 10-year results earlier this year,” Ms. Haviland explained.

FAST-Forward enrolled 4,096 women who had undergone breast-conserving surgery or mastectomy for early invasive breast cancer. The patients were randomized into the aforementioned groups for adjuvant whole-breast or chest-wall radiotherapy: 40 Gy in 15 fractions over 3 weeks, 27 Gy in 5 fractions over 5 days, or 26 Gy in 5 fractions over 5 days. Boosts were permitted for all regimens.
 

Relapse, safety, and patient reports

The median follow-up was 6 years. The 5-year rate of ipsilateral breast tumor relapse was 2.1% with the 40-Gy standard regimen, 1.7% with the 27-Gy hypofractionated regimen, and 1.4% with the 26-Gy hypofractionated regimen.

The upper bound of the 95% confidence interval for the difference comparing the hypofractionated regimens against the standard fell well within the 1.6% excess predefined for noninferiority for both the 27-Gy regimen and the 26-Gy regimen (0.9% and 0.3%, respectively).

The hazard ratio for ipsilateral breast tumor relapse, compared with the standard regimen, was 0.86 for the 27-Gy hypofractionated regimen and 0.67 for the 26-Gy hypofractionated regimen.

In terms of safety, the 5-year rate of late adverse effects of the breast or chest wall – distortion, shrinkage, induration, telangiectasia, or edema – rated as “moderate” or “marked” by clinicians was 10% with the standard regimen, 15% with the 27-Gy regimen (relative risk, 1.55 ; P < .001), and 12% with the 26-Gy regimen (RR, 1.19; P = .17).

Over the entire follow-up, women had significantly higher odds of all moderate or marked individual late adverse effects (except discomfort) with the 27-Gy regimen versus the standard regimen, whereas their odds were significantly higher only for induration and edema with the 26-Gy regimen.

However, absolute rates and risk differences between groups were small, Ms. Haviland pointed out. For example, the most common moderate or marked late adverse effect with the standard regimen was breast shrinkage, seen in 5% of patients, followed by discomfort, seen in 4%.

Patient-assessed change in breast appearance and shrinkage did not differ significantly across groups. But women in the 27-Gy group were more likely than peers in the standard regimen group to report a moderate or marked increase in breast hardness/firmness (21% vs. 14%; P = .008), and women in both the 27-Gy and 26-Gy groups were more likely to report moderate or marked breast swelling (5%; P = .007 and 4%; P = .02, respectively, vs. 2%).
 

A new standard

“We have shown noninferiority in terms of local tumor control for both 5-fraction schedules, compared with the control group of 40 Gy in 15 fractions,” Ms. Haviland summarized. “Late adverse effects in normal tissues were similar after 26 Gy in 5 fractions to 40 Gy in 15 fractions, and although rates were higher for the 27-Gy schedule, we noted that these are consistent with the historic standard of 50 Gy in 25 fractions.”

“There are obvious benefits to patients and health care systems of shorter radiotherapy treatments, particularly at the current time, and in fact, the COVID pandemic has accelerated uptake of the 26-Gy schedule around the world,” she added. “At a recent consensus meeting organized by the Royal College of Radiologists, the U.K. adopted the 26-Gy schedule as a new standard, also integrating this with partial breast irradiation, in close collaboration with the U.K. IMPORT Low trial.”

“This is very important work. I think this is one of the most important trials in the past few years. It has really changed practice,” commented session co-chair Ben Slotman, MD, PhD, of Vrije Universiteit Medical Center, Amsterdam, and AMC Amsterdam, who was not involved the trial.

Dr. Slotman wondered how extensive uptake of the new hypofractionated regimen has been. “I know it’s being used in the U.K. and the Netherlands, but do you have any idea about the rest of Europe? What do we need to make it the new standard?”

“I think there has been uptake in other countries in Europe and elsewhere around the world as well,” Ms. Haviland replied. But feedback suggests adoption has been tempered because of reservations related to the regimen’s safety in certain patient subgroups.

“We haven’t found any cause for concern in the subgroups, and also backed up by meta-analysis in the many patients randomized in the START trials,” she noted. “So I think there is very convincing evidence that it is safe as a new standard.”

FAST-Forward was sponsored by the Institute of Cancer Research and funded by the National Institute for Health Research Health Technology Assessment Programme. Ms. Haviland disclosed no conflicts of interest. Dr. Slotman has relationships with ViewRay and Varian Medical Systems.

SOURCE: Haviland J et al. ESTRO 2020, Abstract OC-0610.

Compared with the standard 3-week regimen, a 1-week hypofractionated regimen of adjuvant whole-breast radiotherapy had similar efficacy and safety at 5 years of follow-up, according to the U.K. FAST-Forward trial.

The trial was designed to compare the standard regimen (40 Gy in 15 fractions over 3 weeks) with a higher-dose hypofractionated regimen (27 Gy in 5 fractions over 5 days) and a lower-dose hypofractionated regimen (26 Gy in 5 fractions over 5 days) in women who had undergone surgery for early invasive breast cancer.

The 5-year rate of ipsilateral breast tumor relapse was similar with all regimens – 2.1% with the 40-Gy regimen, 1.7% with the 27-Gy regimen, and 1.4% with the 26-Gy regimen. The 26-Gy regimen also had similar safety as the 40-Gy regimen.

These results were presented at the European Society for Radiology and Oncology 2020 Online Congress by Joanne S. Haviland, MSc, of the Institute of Cancer Research in London. Results were also published in The Lancet.

Ms. Haviland said that hypofractionated regimens are attractive because of their shorter overall treatment times, which translate to greater convenience and lower treatment costs.

The historic 5-week regimen (50 Gy in 25 fractions) has been replaced by a 3-week regimen (40 Gy in 15 fractions) in the United Kingdom and elsewhere, and ongoing efforts are exploring whether further hypofractionation can be achieved without compromising efficacy and safety.

“The FAST-Forward trial was the next step on from testing hypofractionated schedules evaluated in earlier trials, including the START trials in the early 2000s and the FAST trial, which published its 10-year results earlier this year,” Ms. Haviland explained.

FAST-Forward enrolled 4,096 women who had undergone breast-conserving surgery or mastectomy for early invasive breast cancer. The patients were randomized into the aforementioned groups for adjuvant whole-breast or chest-wall radiotherapy: 40 Gy in 15 fractions over 3 weeks, 27 Gy in 5 fractions over 5 days, or 26 Gy in 5 fractions over 5 days. Boosts were permitted for all regimens.
 

Relapse, safety, and patient reports

The median follow-up was 6 years. The 5-year rate of ipsilateral breast tumor relapse was 2.1% with the 40-Gy standard regimen, 1.7% with the 27-Gy hypofractionated regimen, and 1.4% with the 26-Gy hypofractionated regimen.

The upper bound of the 95% confidence interval for the difference comparing the hypofractionated regimens against the standard fell well within the 1.6% excess predefined for noninferiority for both the 27-Gy regimen and the 26-Gy regimen (0.9% and 0.3%, respectively).

The hazard ratio for ipsilateral breast tumor relapse, compared with the standard regimen, was 0.86 for the 27-Gy hypofractionated regimen and 0.67 for the 26-Gy hypofractionated regimen.

In terms of safety, the 5-year rate of late adverse effects of the breast or chest wall – distortion, shrinkage, induration, telangiectasia, or edema – rated as “moderate” or “marked” by clinicians was 10% with the standard regimen, 15% with the 27-Gy regimen (relative risk, 1.55 ; P < .001), and 12% with the 26-Gy regimen (RR, 1.19; P = .17).

Over the entire follow-up, women had significantly higher odds of all moderate or marked individual late adverse effects (except discomfort) with the 27-Gy regimen versus the standard regimen, whereas their odds were significantly higher only for induration and edema with the 26-Gy regimen.

However, absolute rates and risk differences between groups were small, Ms. Haviland pointed out. For example, the most common moderate or marked late adverse effect with the standard regimen was breast shrinkage, seen in 5% of patients, followed by discomfort, seen in 4%.

Patient-assessed change in breast appearance and shrinkage did not differ significantly across groups. But women in the 27-Gy group were more likely than peers in the standard regimen group to report a moderate or marked increase in breast hardness/firmness (21% vs. 14%; P = .008), and women in both the 27-Gy and 26-Gy groups were more likely to report moderate or marked breast swelling (5%; P = .007 and 4%; P = .02, respectively, vs. 2%).
 

A new standard

“We have shown noninferiority in terms of local tumor control for both 5-fraction schedules, compared with the control group of 40 Gy in 15 fractions,” Ms. Haviland summarized. “Late adverse effects in normal tissues were similar after 26 Gy in 5 fractions to 40 Gy in 15 fractions, and although rates were higher for the 27-Gy schedule, we noted that these are consistent with the historic standard of 50 Gy in 25 fractions.”

“There are obvious benefits to patients and health care systems of shorter radiotherapy treatments, particularly at the current time, and in fact, the COVID pandemic has accelerated uptake of the 26-Gy schedule around the world,” she added. “At a recent consensus meeting organized by the Royal College of Radiologists, the U.K. adopted the 26-Gy schedule as a new standard, also integrating this with partial breast irradiation, in close collaboration with the U.K. IMPORT Low trial.”

“This is very important work. I think this is one of the most important trials in the past few years. It has really changed practice,” commented session co-chair Ben Slotman, MD, PhD, of Vrije Universiteit Medical Center, Amsterdam, and AMC Amsterdam, who was not involved the trial.

Dr. Slotman wondered how extensive uptake of the new hypofractionated regimen has been. “I know it’s being used in the U.K. and the Netherlands, but do you have any idea about the rest of Europe? What do we need to make it the new standard?”

“I think there has been uptake in other countries in Europe and elsewhere around the world as well,” Ms. Haviland replied. But feedback suggests adoption has been tempered because of reservations related to the regimen’s safety in certain patient subgroups.

“We haven’t found any cause for concern in the subgroups, and also backed up by meta-analysis in the many patients randomized in the START trials,” she noted. “So I think there is very convincing evidence that it is safe as a new standard.”

FAST-Forward was sponsored by the Institute of Cancer Research and funded by the National Institute for Health Research Health Technology Assessment Programme. Ms. Haviland disclosed no conflicts of interest. Dr. Slotman has relationships with ViewRay and Varian Medical Systems.

SOURCE: Haviland J et al. ESTRO 2020, Abstract OC-0610.

Compared with the standard 3-week regimen, a 1-week hypofractionated regimen of adjuvant whole-breast radiotherapy had similar efficacy and safety at 5 years of follow-up, according to the U.K. FAST-Forward trial.

The trial was designed to compare the standard regimen (40 Gy in 15 fractions over 3 weeks) with a higher-dose hypofractionated regimen (27 Gy in 5 fractions over 5 days) and a lower-dose hypofractionated regimen (26 Gy in 5 fractions over 5 days) in women who had undergone surgery for early invasive breast cancer.

The 5-year rate of ipsilateral breast tumor relapse was similar with all regimens – 2.1% with the 40-Gy regimen, 1.7% with the 27-Gy regimen, and 1.4% with the 26-Gy regimen. The 26-Gy regimen also had similar safety as the 40-Gy regimen.

These results were presented at the European Society for Radiology and Oncology 2020 Online Congress by Joanne S. Haviland, MSc, of the Institute of Cancer Research in London. Results were also published in The Lancet.

Ms. Haviland said that hypofractionated regimens are attractive because of their shorter overall treatment times, which translate to greater convenience and lower treatment costs.

The historic 5-week regimen (50 Gy in 25 fractions) has been replaced by a 3-week regimen (40 Gy in 15 fractions) in the United Kingdom and elsewhere, and ongoing efforts are exploring whether further hypofractionation can be achieved without compromising efficacy and safety.

“The FAST-Forward trial was the next step on from testing hypofractionated schedules evaluated in earlier trials, including the START trials in the early 2000s and the FAST trial, which published its 10-year results earlier this year,” Ms. Haviland explained.

FAST-Forward enrolled 4,096 women who had undergone breast-conserving surgery or mastectomy for early invasive breast cancer. The patients were randomized into the aforementioned groups for adjuvant whole-breast or chest-wall radiotherapy: 40 Gy in 15 fractions over 3 weeks, 27 Gy in 5 fractions over 5 days, or 26 Gy in 5 fractions over 5 days. Boosts were permitted for all regimens.
 

Relapse, safety, and patient reports

The median follow-up was 6 years. The 5-year rate of ipsilateral breast tumor relapse was 2.1% with the 40-Gy standard regimen, 1.7% with the 27-Gy hypofractionated regimen, and 1.4% with the 26-Gy hypofractionated regimen.

The upper bound of the 95% confidence interval for the difference comparing the hypofractionated regimens against the standard fell well within the 1.6% excess predefined for noninferiority for both the 27-Gy regimen and the 26-Gy regimen (0.9% and 0.3%, respectively).

The hazard ratio for ipsilateral breast tumor relapse, compared with the standard regimen, was 0.86 for the 27-Gy hypofractionated regimen and 0.67 for the 26-Gy hypofractionated regimen.

In terms of safety, the 5-year rate of late adverse effects of the breast or chest wall – distortion, shrinkage, induration, telangiectasia, or edema – rated as “moderate” or “marked” by clinicians was 10% with the standard regimen, 15% with the 27-Gy regimen (relative risk, 1.55 ; P < .001), and 12% with the 26-Gy regimen (RR, 1.19; P = .17).

Over the entire follow-up, women had significantly higher odds of all moderate or marked individual late adverse effects (except discomfort) with the 27-Gy regimen versus the standard regimen, whereas their odds were significantly higher only for induration and edema with the 26-Gy regimen.

However, absolute rates and risk differences between groups were small, Ms. Haviland pointed out. For example, the most common moderate or marked late adverse effect with the standard regimen was breast shrinkage, seen in 5% of patients, followed by discomfort, seen in 4%.

Patient-assessed change in breast appearance and shrinkage did not differ significantly across groups. But women in the 27-Gy group were more likely than peers in the standard regimen group to report a moderate or marked increase in breast hardness/firmness (21% vs. 14%; P = .008), and women in both the 27-Gy and 26-Gy groups were more likely to report moderate or marked breast swelling (5%; P = .007 and 4%; P = .02, respectively, vs. 2%).
 

A new standard

“We have shown noninferiority in terms of local tumor control for both 5-fraction schedules, compared with the control group of 40 Gy in 15 fractions,” Ms. Haviland summarized. “Late adverse effects in normal tissues were similar after 26 Gy in 5 fractions to 40 Gy in 15 fractions, and although rates were higher for the 27-Gy schedule, we noted that these are consistent with the historic standard of 50 Gy in 25 fractions.”

“There are obvious benefits to patients and health care systems of shorter radiotherapy treatments, particularly at the current time, and in fact, the COVID pandemic has accelerated uptake of the 26-Gy schedule around the world,” she added. “At a recent consensus meeting organized by the Royal College of Radiologists, the U.K. adopted the 26-Gy schedule as a new standard, also integrating this with partial breast irradiation, in close collaboration with the U.K. IMPORT Low trial.”

“This is very important work. I think this is one of the most important trials in the past few years. It has really changed practice,” commented session co-chair Ben Slotman, MD, PhD, of Vrije Universiteit Medical Center, Amsterdam, and AMC Amsterdam, who was not involved the trial.

Dr. Slotman wondered how extensive uptake of the new hypofractionated regimen has been. “I know it’s being used in the U.K. and the Netherlands, but do you have any idea about the rest of Europe? What do we need to make it the new standard?”

“I think there has been uptake in other countries in Europe and elsewhere around the world as well,” Ms. Haviland replied. But feedback suggests adoption has been tempered because of reservations related to the regimen’s safety in certain patient subgroups.

“We haven’t found any cause for concern in the subgroups, and also backed up by meta-analysis in the many patients randomized in the START trials,” she noted. “So I think there is very convincing evidence that it is safe as a new standard.”

FAST-Forward was sponsored by the Institute of Cancer Research and funded by the National Institute for Health Research Health Technology Assessment Programme. Ms. Haviland disclosed no conflicts of interest. Dr. Slotman has relationships with ViewRay and Varian Medical Systems.

SOURCE: Haviland J et al. ESTRO 2020, Abstract OC-0610.

MRI-guided adaptive brachytherapy yields promising long-term outcomes in locally advanced cervical cancer but needs refinement to reduce morbidity and improve efficacy for certain patients, the EMBRACE I study suggests.

At 5 years, the rate of local control was 92%, and overall survival was 74%. However, nodal and systemic control rates were inferior for node-positive and high-risk patients, and nearly 15% of patients experienced grade 3-5 treatment-related morbidity.

These results were reported at the European Society for Radiology and Oncology 2020 Online Congress.

Historically, brachytherapy dose has been fairly rigidly prescribed, based on dose points defined in two dimensions. By performing imaging before each brachytherapy implant, treatment parameters can be adapted to a patient’s anatomy, taking into account the positions of organs at risk and any tumor regression from prior treatment.

Richard Pötter, MD, emeritus professor at Medical University of Vienna, and colleagues tested MRI-guided adaptive brachytherapy in a multicenter cohort study.

The study’s disease outcome analysis included 1,341 women with cervical cancer of International Federation of Gynecology and Obstetrics stage IB–IVB (52% node positive) being treated with curative intent.

The women underwent definitive external beam radiotherapy (45-50 Gy, using either three-dimensional–conformal radiotherapy or intensity-modulated radiotherapy) with concurrent cisplatin chemotherapy, followed by MRI-guided adaptive brachytherapy based on MRI with the applicator in situ.

“There was no fixed dose prescription for brachytherapy, and there were no constraints for organs at risk,” Dr. Pötter explained. “But there was systematic joint reporting and contouring for the target and organs at risk, and also for doses and volumes.”

Nearly all patients were treated with adaptive MRI-based target and dose-volume and point parameters (99.1%), as well as with individualized multiparametric dose optimization (98.2%). The application technique was adapted, with intracavitary application alone used in 57% of patients, and both intracavitary and interstitial application in 43%.
 

Efficacy and toxicity

At a median follow-up of 51 months, 7.3% of patients had experienced a local failure, with 3.8% having an isolated local failure and 3.5% having synchronous nodal or systemic failure, Dr. Pötter reported.

The local failure rate was similar going from disease stage IB2 to IVA (8%-9%), even though the target volume more than doubled.

“This favorable result was due to an adaptation of dose, which was quite similar for the different stages and volumes. This is a major message of EMBRACE I,” Dr. Pötter commented.

The Kaplan-Meier–estimated 5-year rate of local control was 92% for the whole cohort. It was 98% in patients with stage IB1 disease and 91%-92% in patients with stage IB2–IVA disease.

The 5-year rate of overall survival was 74% for the entire cohort. It fell with stage, from 83% in patients with stage IB1 disease to 52% in patients with stage IVA disease.

For the entire population, the 5-year pelvic control rate was 87%, the 5-year cancer-specific survival was 79%, and the 5-year disease-free survival was 68%.

Overall, 14.6% of patients experienced grade 3-5 treatment-related morbidity at 5 years: 2.7% developed fistulas, 6.1% had vaginal toxicity, 6.5% had genitourinary toxicity, and 7.6% had gastrointestinal toxicity.
 

Room for improvement

“MRI-guided adaptive brachytherapy in locally advanced cervical cancer works in multicenter clinical practice, within such a study, with adaptation of the target and application technique, and multiparametric treatment planning and dose prescription,” Dr. Pötter summarized.

However, “the mature clinical outcomes appear challenging,” he added. Specifically, although the rate of local control was high, the rate of nodal control left room for improvement in node-positive patients, and the rates of systemic control and overall survival left room for improvement in high-risk patients.

In addition, “the grade 3-5 morbidity was limited per organ and per endpoint, but was considerable overall, and this asks for a reduction,” Dr. Pötter said.

Two of the areas needing improvement are being addressed in ongoing and planned research, according to Dr. Pötter. “The nodal part is already being addressed in EMBRACE II, intensifying treatment for node-positive patients through a simultaneous integrated boost and a very sophisticated probability planning concept, and also including more patients for paraaortic radiotherapy,” he elaborated. “For the systemic part, we have thought about [a study testing an] additional drug ... and there are thoughts for EMBRACE III to investigate such effect.”
 

A benchmark for brachytherapy

“This is the largest prospective cohort of patients treated with image-guided brachytherapy. The high rates of local control with long-term follow-up are impressive and speak to the clear value of high-quality brachytherapy,” commented Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, who was not involved in this study.

With its consistent reporting of detailed dose and toxicity data, the study establishes a benchmark for brachytherapy worldwide, Dr. Klopp said. It also better informs treatment decision-making in cases where replacing brachytherapy with external beam techniques is being considered.

Although MRI guidance is increasingly being used in brachytherapy, the latest studies on patterns of care suggest that overall use is still low, according to Dr. Klopp.

“The challenges are primarily logistical,” she elaborated. “MRI-compatible applicators must be placed, and patients need to wait for the scans to be performed, which can take an hour or more. In addition, the times that patients get scanned can be unpredictable based on procedure times, which can create practical challenges for scheduling. In some cases, cost may also be a deterrent.

“The bar is high for brachytherapy. It’s an excellent treatment modality that provides very high rates of local control with very low toxicity when done optimally,” Dr. Klopp concluded. “I do think that this experience provides very convincing evidence that the best brachytherapy is image-guided and requires care to monitor normal tissue doses in order to reduce the risk of long-term toxicity.”

The study was supported by unrestricted grants from Elekta and Varian. Dr. Pötter and Dr. Klopp disclosed no conflicts of interest.

SOURCE: Pötter R et al. ESTRO 2020, Abstract OC-0437.

MRI-guided adaptive brachytherapy yields promising long-term outcomes in locally advanced cervical cancer but needs refinement to reduce morbidity and improve efficacy for certain patients, the EMBRACE I study suggests.

At 5 years, the rate of local control was 92%, and overall survival was 74%. However, nodal and systemic control rates were inferior for node-positive and high-risk patients, and nearly 15% of patients experienced grade 3-5 treatment-related morbidity.

These results were reported at the European Society for Radiology and Oncology 2020 Online Congress.

Historically, brachytherapy dose has been fairly rigidly prescribed, based on dose points defined in two dimensions. By performing imaging before each brachytherapy implant, treatment parameters can be adapted to a patient’s anatomy, taking into account the positions of organs at risk and any tumor regression from prior treatment.

Richard Pötter, MD, emeritus professor at Medical University of Vienna, and colleagues tested MRI-guided adaptive brachytherapy in a multicenter cohort study.

The study’s disease outcome analysis included 1,341 women with cervical cancer of International Federation of Gynecology and Obstetrics stage IB–IVB (52% node positive) being treated with curative intent.

The women underwent definitive external beam radiotherapy (45-50 Gy, using either three-dimensional–conformal radiotherapy or intensity-modulated radiotherapy) with concurrent cisplatin chemotherapy, followed by MRI-guided adaptive brachytherapy based on MRI with the applicator in situ.

“There was no fixed dose prescription for brachytherapy, and there were no constraints for organs at risk,” Dr. Pötter explained. “But there was systematic joint reporting and contouring for the target and organs at risk, and also for doses and volumes.”

Nearly all patients were treated with adaptive MRI-based target and dose-volume and point parameters (99.1%), as well as with individualized multiparametric dose optimization (98.2%). The application technique was adapted, with intracavitary application alone used in 57% of patients, and both intracavitary and interstitial application in 43%.
 

Efficacy and toxicity

At a median follow-up of 51 months, 7.3% of patients had experienced a local failure, with 3.8% having an isolated local failure and 3.5% having synchronous nodal or systemic failure, Dr. Pötter reported.

The local failure rate was similar going from disease stage IB2 to IVA (8%-9%), even though the target volume more than doubled.

“This favorable result was due to an adaptation of dose, which was quite similar for the different stages and volumes. This is a major message of EMBRACE I,” Dr. Pötter commented.

The Kaplan-Meier–estimated 5-year rate of local control was 92% for the whole cohort. It was 98% in patients with stage IB1 disease and 91%-92% in patients with stage IB2–IVA disease.

The 5-year rate of overall survival was 74% for the entire cohort. It fell with stage, from 83% in patients with stage IB1 disease to 52% in patients with stage IVA disease.

For the entire population, the 5-year pelvic control rate was 87%, the 5-year cancer-specific survival was 79%, and the 5-year disease-free survival was 68%.

Overall, 14.6% of patients experienced grade 3-5 treatment-related morbidity at 5 years: 2.7% developed fistulas, 6.1% had vaginal toxicity, 6.5% had genitourinary toxicity, and 7.6% had gastrointestinal toxicity.
 

Room for improvement

“MRI-guided adaptive brachytherapy in locally advanced cervical cancer works in multicenter clinical practice, within such a study, with adaptation of the target and application technique, and multiparametric treatment planning and dose prescription,” Dr. Pötter summarized.

However, “the mature clinical outcomes appear challenging,” he added. Specifically, although the rate of local control was high, the rate of nodal control left room for improvement in node-positive patients, and the rates of systemic control and overall survival left room for improvement in high-risk patients.

In addition, “the grade 3-5 morbidity was limited per organ and per endpoint, but was considerable overall, and this asks for a reduction,” Dr. Pötter said.

Two of the areas needing improvement are being addressed in ongoing and planned research, according to Dr. Pötter. “The nodal part is already being addressed in EMBRACE II, intensifying treatment for node-positive patients through a simultaneous integrated boost and a very sophisticated probability planning concept, and also including more patients for paraaortic radiotherapy,” he elaborated. “For the systemic part, we have thought about [a study testing an] additional drug ... and there are thoughts for EMBRACE III to investigate such effect.”
 

A benchmark for brachytherapy

“This is the largest prospective cohort of patients treated with image-guided brachytherapy. The high rates of local control with long-term follow-up are impressive and speak to the clear value of high-quality brachytherapy,” commented Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, who was not involved in this study.

With its consistent reporting of detailed dose and toxicity data, the study establishes a benchmark for brachytherapy worldwide, Dr. Klopp said. It also better informs treatment decision-making in cases where replacing brachytherapy with external beam techniques is being considered.

Although MRI guidance is increasingly being used in brachytherapy, the latest studies on patterns of care suggest that overall use is still low, according to Dr. Klopp.

“The challenges are primarily logistical,” she elaborated. “MRI-compatible applicators must be placed, and patients need to wait for the scans to be performed, which can take an hour or more. In addition, the times that patients get scanned can be unpredictable based on procedure times, which can create practical challenges for scheduling. In some cases, cost may also be a deterrent.

“The bar is high for brachytherapy. It’s an excellent treatment modality that provides very high rates of local control with very low toxicity when done optimally,” Dr. Klopp concluded. “I do think that this experience provides very convincing evidence that the best brachytherapy is image-guided and requires care to monitor normal tissue doses in order to reduce the risk of long-term toxicity.”

The study was supported by unrestricted grants from Elekta and Varian. Dr. Pötter and Dr. Klopp disclosed no conflicts of interest.

SOURCE: Pötter R et al. ESTRO 2020, Abstract OC-0437.

MRI-guided adaptive brachytherapy yields promising long-term outcomes in locally advanced cervical cancer but needs refinement to reduce morbidity and improve efficacy for certain patients, the EMBRACE I study suggests.

At 5 years, the rate of local control was 92%, and overall survival was 74%. However, nodal and systemic control rates were inferior for node-positive and high-risk patients, and nearly 15% of patients experienced grade 3-5 treatment-related morbidity.

These results were reported at the European Society for Radiology and Oncology 2020 Online Congress.

Historically, brachytherapy dose has been fairly rigidly prescribed, based on dose points defined in two dimensions. By performing imaging before each brachytherapy implant, treatment parameters can be adapted to a patient’s anatomy, taking into account the positions of organs at risk and any tumor regression from prior treatment.

Richard Pötter, MD, emeritus professor at Medical University of Vienna, and colleagues tested MRI-guided adaptive brachytherapy in a multicenter cohort study.

The study’s disease outcome analysis included 1,341 women with cervical cancer of International Federation of Gynecology and Obstetrics stage IB–IVB (52% node positive) being treated with curative intent.

The women underwent definitive external beam radiotherapy (45-50 Gy, using either three-dimensional–conformal radiotherapy or intensity-modulated radiotherapy) with concurrent cisplatin chemotherapy, followed by MRI-guided adaptive brachytherapy based on MRI with the applicator in situ.

“There was no fixed dose prescription for brachytherapy, and there were no constraints for organs at risk,” Dr. Pötter explained. “But there was systematic joint reporting and contouring for the target and organs at risk, and also for doses and volumes.”

Nearly all patients were treated with adaptive MRI-based target and dose-volume and point parameters (99.1%), as well as with individualized multiparametric dose optimization (98.2%). The application technique was adapted, with intracavitary application alone used in 57% of patients, and both intracavitary and interstitial application in 43%.
 

Efficacy and toxicity

At a median follow-up of 51 months, 7.3% of patients had experienced a local failure, with 3.8% having an isolated local failure and 3.5% having synchronous nodal or systemic failure, Dr. Pötter reported.

The local failure rate was similar going from disease stage IB2 to IVA (8%-9%), even though the target volume more than doubled.

“This favorable result was due to an adaptation of dose, which was quite similar for the different stages and volumes. This is a major message of EMBRACE I,” Dr. Pötter commented.

The Kaplan-Meier–estimated 5-year rate of local control was 92% for the whole cohort. It was 98% in patients with stage IB1 disease and 91%-92% in patients with stage IB2–IVA disease.

The 5-year rate of overall survival was 74% for the entire cohort. It fell with stage, from 83% in patients with stage IB1 disease to 52% in patients with stage IVA disease.

For the entire population, the 5-year pelvic control rate was 87%, the 5-year cancer-specific survival was 79%, and the 5-year disease-free survival was 68%.

Overall, 14.6% of patients experienced grade 3-5 treatment-related morbidity at 5 years: 2.7% developed fistulas, 6.1% had vaginal toxicity, 6.5% had genitourinary toxicity, and 7.6% had gastrointestinal toxicity.
 

Room for improvement

“MRI-guided adaptive brachytherapy in locally advanced cervical cancer works in multicenter clinical practice, within such a study, with adaptation of the target and application technique, and multiparametric treatment planning and dose prescription,” Dr. Pötter summarized.

However, “the mature clinical outcomes appear challenging,” he added. Specifically, although the rate of local control was high, the rate of nodal control left room for improvement in node-positive patients, and the rates of systemic control and overall survival left room for improvement in high-risk patients.

In addition, “the grade 3-5 morbidity was limited per organ and per endpoint, but was considerable overall, and this asks for a reduction,” Dr. Pötter said.

Two of the areas needing improvement are being addressed in ongoing and planned research, according to Dr. Pötter. “The nodal part is already being addressed in EMBRACE II, intensifying treatment for node-positive patients through a simultaneous integrated boost and a very sophisticated probability planning concept, and also including more patients for paraaortic radiotherapy,” he elaborated. “For the systemic part, we have thought about [a study testing an] additional drug ... and there are thoughts for EMBRACE III to investigate such effect.”
 

A benchmark for brachytherapy

“This is the largest prospective cohort of patients treated with image-guided brachytherapy. The high rates of local control with long-term follow-up are impressive and speak to the clear value of high-quality brachytherapy,” commented Ann H. Klopp, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, who was not involved in this study.

With its consistent reporting of detailed dose and toxicity data, the study establishes a benchmark for brachytherapy worldwide, Dr. Klopp said. It also better informs treatment decision-making in cases where replacing brachytherapy with external beam techniques is being considered.

Although MRI guidance is increasingly being used in brachytherapy, the latest studies on patterns of care suggest that overall use is still low, according to Dr. Klopp.

“The challenges are primarily logistical,” she elaborated. “MRI-compatible applicators must be placed, and patients need to wait for the scans to be performed, which can take an hour or more. In addition, the times that patients get scanned can be unpredictable based on procedure times, which can create practical challenges for scheduling. In some cases, cost may also be a deterrent.

“The bar is high for brachytherapy. It’s an excellent treatment modality that provides very high rates of local control with very low toxicity when done optimally,” Dr. Klopp concluded. “I do think that this experience provides very convincing evidence that the best brachytherapy is image-guided and requires care to monitor normal tissue doses in order to reduce the risk of long-term toxicity.”

The study was supported by unrestricted grants from Elekta and Varian. Dr. Pötter and Dr. Klopp disclosed no conflicts of interest.

SOURCE: Pötter R et al. ESTRO 2020, Abstract OC-0437.

The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress. 

“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.

In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.

“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.

PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.

“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.

The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.

For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.

“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.

The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.

The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.

With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.

With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.

The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).

“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.

In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.

“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.

The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.

“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.

The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.

Not ready for prime time

“Overall, this study conceptually is well designed as it is forward thinking and uses imaging to personalize radiation treatment, going to higher doses to active areas of disease based on FDG-PET imaging,” Arya Amini, MD, assistant clinical professor in the department of radiation oncology, City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

SOURCE: Lalezari F et al. ESTRO 2020. Abstract OC-0609.

The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress. 

“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.

In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.

“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.

PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.

“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.

The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.

For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.

“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.

The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.

The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.

With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.

With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.

The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).

“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.

In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.

“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.

The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.

“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.

The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.

Not ready for prime time

“Overall, this study conceptually is well designed as it is forward thinking and uses imaging to personalize radiation treatment, going to higher doses to active areas of disease based on FDG-PET imaging,” Arya Amini, MD, assistant clinical professor in the department of radiation oncology, City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

SOURCE: Lalezari F et al. ESTRO 2020. Abstract OC-0609.

The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress. 

“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.

In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.

“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.

PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.

“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.

The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.

For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.

“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.

The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.

The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.

With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.

With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.

The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).

“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.

In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.

“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.

The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.

“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.

The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.

Not ready for prime time

“Overall, this study conceptually is well designed as it is forward thinking and uses imaging to personalize radiation treatment, going to higher doses to active areas of disease based on FDG-PET imaging,” Arya Amini, MD, assistant clinical professor in the department of radiation oncology, City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

SOURCE: Lalezari F et al. ESTRO 2020. Abstract OC-0609.

Long-term cosmetic and toxicity outcomes are good for both accelerated partial breast irradiation (APBI) delivered with 3D-conformal radiotherapy and whole-breast irradiation (WBI), with the latter having a slight edge, the IRMA trial shows.

Findings were reported at the European Society for Radiology and Oncology 2020 Online Congress by Bruno Meduri, MD, a radiation oncologist at University Hospital of Modena, Italy.

Uptake of APBI has increased since it was approved nearly 2 decades ago. However, its long-term outcomes are still being parsed, and issues such as appropriate patient selection and optimal delivery technique are still being clarified (Curr Breast Cancer Rep. 2020;18:1-10).

IRMA is a European, multicenter, phase 3 randomized controlled trial conducted among 3,279 women aged 49 years and older who underwent breast-conserving surgery for early-stage breast cancer (measuring <3 cm in diameter, and pathologic N0 or N1) with negative resection margins.

The women were randomized to APBI using 3D-conformal radiotherapy (38.5 Gy in 10 fractions, twice daily) or conventional or hypofractionated WBI (50.0 Gy in 25 fractions, once daily). All additionally received adjuvant therapy according to institutional guidelines.

Patients and physicians separately rated cosmetic outcomes on a 4-point scale using the untreated breast as a reference, and toxicity was graded with the Radiation Therapy Oncology Group (RTOG) scale.

Over a median follow-up of 5 years, patients rated cosmesis more favorably than physicians did at all time points, and there was a trend toward slight worsening of cosmesis in the APBI group with time, Dr. Meduri reported.

At 1 year, cosmesis did not differ significantly between treatment groups regardless of the rater. But compared with the WBI group, the APBI group more often had patient-rated fair to poor cosmesis at 3 years (12.7% vs. 9.4%; P =.02) and at 5 years (15.0% vs. 10.1%; P = .007), as well as physician-rated fair to poor cosmesis at 3 years (18.0% vs. 13.1%; P = .003) and at 5 years (18.4% vs. 14.2%; P = .04).

Women treated with APBI had less acute skin toxicity (P < .001), with 4.9% developing grade 2 toxicity, compared with 21.4% of peers treated with WBI. Late skin toxicity was also less common in the APBI group overall (P < .001), but the rate of grade 3 or 4 late skin toxicity was similar.

On the other hand, the APBI group had more late bone toxicity overall (P < .001) and late bone toxicity of grade 3 or 4 (1.0% vs. 0%; P < .05), as well as more late soft tissue (subcutaneous) toxicity overall (P < .001) and late soft tissue toxicity of grade 3 or 4 (2.6% vs. 1.1%; P < .05).

The two groups had essentially the same late lung toxicity.

Women treated with APBI had higher 5-year cumulative incidences of soft tissue toxicity of grade 2 or worse (29.7% vs. 17.9%; P < .0001) and grade 3 or worse (2.6% vs. 1.1%; P = .0016). Cumulative incidences of skin toxicity of these grades did not differ significantly.

Importantly, the prevalences of late soft tissue and skin toxicity at 5 years were much lower than the cumulative incidences, Dr. Meduri noted. “This means that the side effects in some patients tend to resolve over time.”

Although the prevalence of grade 2-4 skin toxicity increased slightly at 3 years and 5 years in both groups, the prevalence of grade 2-4 soft tissue toxicity was stable.

Finally, the volume that received at least 38.5 Gy of radiation was higher for patients who developed late grade 3 or 4 bone toxicity than for those who did not (2.1 vs. 0.82 cc; P = .027), whereas other dosimetric parameters were similar.

“The toxicity of the whole cohort was very low,” Dr. Meduri summarized. “APBI was associated with a slightly higher rate of late soft tissue and bone toxicity, with a slight decrease in cosmetic outcome at 5 years. But longer follow-up is needed to confirm these results.”

The IRMA findings confirm previous results from the RAPID trial showing that APBI delivered via 3D-conformal radiotherapy may be associated with increased rates of toxicity, Chirag Shah, MD, a radiation oncologist at the Cleveland Clinic in Ohio, said in an interview.

SOURCE: Meduri B et al. ESTRO 2020. Abstract OC-0611.

Long-term cosmetic and toxicity outcomes are good for both accelerated partial breast irradiation (APBI) delivered with 3D-conformal radiotherapy and whole-breast irradiation (WBI), with the latter having a slight edge, the IRMA trial shows.

Findings were reported at the European Society for Radiology and Oncology 2020 Online Congress by Bruno Meduri, MD, a radiation oncologist at University Hospital of Modena, Italy.

Uptake of APBI has increased since it was approved nearly 2 decades ago. However, its long-term outcomes are still being parsed, and issues such as appropriate patient selection and optimal delivery technique are still being clarified (Curr Breast Cancer Rep. 2020;18:1-10).

IRMA is a European, multicenter, phase 3 randomized controlled trial conducted among 3,279 women aged 49 years and older who underwent breast-conserving surgery for early-stage breast cancer (measuring <3 cm in diameter, and pathologic N0 or N1) with negative resection margins.

The women were randomized to APBI using 3D-conformal radiotherapy (38.5 Gy in 10 fractions, twice daily) or conventional or hypofractionated WBI (50.0 Gy in 25 fractions, once daily). All additionally received adjuvant therapy according to institutional guidelines.

Patients and physicians separately rated cosmetic outcomes on a 4-point scale using the untreated breast as a reference, and toxicity was graded with the Radiation Therapy Oncology Group (RTOG) scale.

Over a median follow-up of 5 years, patients rated cosmesis more favorably than physicians did at all time points, and there was a trend toward slight worsening of cosmesis in the APBI group with time, Dr. Meduri reported.

At 1 year, cosmesis did not differ significantly between treatment groups regardless of the rater. But compared with the WBI group, the APBI group more often had patient-rated fair to poor cosmesis at 3 years (12.7% vs. 9.4%; P =.02) and at 5 years (15.0% vs. 10.1%; P = .007), as well as physician-rated fair to poor cosmesis at 3 years (18.0% vs. 13.1%; P = .003) and at 5 years (18.4% vs. 14.2%; P = .04).

Women treated with APBI had less acute skin toxicity (P < .001), with 4.9% developing grade 2 toxicity, compared with 21.4% of peers treated with WBI. Late skin toxicity was also less common in the APBI group overall (P < .001), but the rate of grade 3 or 4 late skin toxicity was similar.

On the other hand, the APBI group had more late bone toxicity overall (P < .001) and late bone toxicity of grade 3 or 4 (1.0% vs. 0%; P < .05), as well as more late soft tissue (subcutaneous) toxicity overall (P < .001) and late soft tissue toxicity of grade 3 or 4 (2.6% vs. 1.1%; P < .05).

The two groups had essentially the same late lung toxicity.

Women treated with APBI had higher 5-year cumulative incidences of soft tissue toxicity of grade 2 or worse (29.7% vs. 17.9%; P < .0001) and grade 3 or worse (2.6% vs. 1.1%; P = .0016). Cumulative incidences of skin toxicity of these grades did not differ significantly.

Importantly, the prevalences of late soft tissue and skin toxicity at 5 years were much lower than the cumulative incidences, Dr. Meduri noted. “This means that the side effects in some patients tend to resolve over time.”

Although the prevalence of grade 2-4 skin toxicity increased slightly at 3 years and 5 years in both groups, the prevalence of grade 2-4 soft tissue toxicity was stable.

Finally, the volume that received at least 38.5 Gy of radiation was higher for patients who developed late grade 3 or 4 bone toxicity than for those who did not (2.1 vs. 0.82 cc; P = .027), whereas other dosimetric parameters were similar.

“The toxicity of the whole cohort was very low,” Dr. Meduri summarized. “APBI was associated with a slightly higher rate of late soft tissue and bone toxicity, with a slight decrease in cosmetic outcome at 5 years. But longer follow-up is needed to confirm these results.”

The IRMA findings confirm previous results from the RAPID trial showing that APBI delivered via 3D-conformal radiotherapy may be associated with increased rates of toxicity, Chirag Shah, MD, a radiation oncologist at the Cleveland Clinic in Ohio, said in an interview.

SOURCE: Meduri B et al. ESTRO 2020. Abstract OC-0611.

Long-term cosmetic and toxicity outcomes are good for both accelerated partial breast irradiation (APBI) delivered with 3D-conformal radiotherapy and whole-breast irradiation (WBI), with the latter having a slight edge, the IRMA trial shows.

Findings were reported at the European Society for Radiology and Oncology 2020 Online Congress by Bruno Meduri, MD, a radiation oncologist at University Hospital of Modena, Italy.

Uptake of APBI has increased since it was approved nearly 2 decades ago. However, its long-term outcomes are still being parsed, and issues such as appropriate patient selection and optimal delivery technique are still being clarified (Curr Breast Cancer Rep. 2020;18:1-10).

IRMA is a European, multicenter, phase 3 randomized controlled trial conducted among 3,279 women aged 49 years and older who underwent breast-conserving surgery for early-stage breast cancer (measuring <3 cm in diameter, and pathologic N0 or N1) with negative resection margins.

The women were randomized to APBI using 3D-conformal radiotherapy (38.5 Gy in 10 fractions, twice daily) or conventional or hypofractionated WBI (50.0 Gy in 25 fractions, once daily). All additionally received adjuvant therapy according to institutional guidelines.

Patients and physicians separately rated cosmetic outcomes on a 4-point scale using the untreated breast as a reference, and toxicity was graded with the Radiation Therapy Oncology Group (RTOG) scale.

Over a median follow-up of 5 years, patients rated cosmesis more favorably than physicians did at all time points, and there was a trend toward slight worsening of cosmesis in the APBI group with time, Dr. Meduri reported.

At 1 year, cosmesis did not differ significantly between treatment groups regardless of the rater. But compared with the WBI group, the APBI group more often had patient-rated fair to poor cosmesis at 3 years (12.7% vs. 9.4%; P =.02) and at 5 years (15.0% vs. 10.1%; P = .007), as well as physician-rated fair to poor cosmesis at 3 years (18.0% vs. 13.1%; P = .003) and at 5 years (18.4% vs. 14.2%; P = .04).

Women treated with APBI had less acute skin toxicity (P < .001), with 4.9% developing grade 2 toxicity, compared with 21.4% of peers treated with WBI. Late skin toxicity was also less common in the APBI group overall (P < .001), but the rate of grade 3 or 4 late skin toxicity was similar.

On the other hand, the APBI group had more late bone toxicity overall (P < .001) and late bone toxicity of grade 3 or 4 (1.0% vs. 0%; P < .05), as well as more late soft tissue (subcutaneous) toxicity overall (P < .001) and late soft tissue toxicity of grade 3 or 4 (2.6% vs. 1.1%; P < .05).

The two groups had essentially the same late lung toxicity.

Women treated with APBI had higher 5-year cumulative incidences of soft tissue toxicity of grade 2 or worse (29.7% vs. 17.9%; P < .0001) and grade 3 or worse (2.6% vs. 1.1%; P = .0016). Cumulative incidences of skin toxicity of these grades did not differ significantly.

Importantly, the prevalences of late soft tissue and skin toxicity at 5 years were much lower than the cumulative incidences, Dr. Meduri noted. “This means that the side effects in some patients tend to resolve over time.”

Although the prevalence of grade 2-4 skin toxicity increased slightly at 3 years and 5 years in both groups, the prevalence of grade 2-4 soft tissue toxicity was stable.

Finally, the volume that received at least 38.5 Gy of radiation was higher for patients who developed late grade 3 or 4 bone toxicity than for those who did not (2.1 vs. 0.82 cc; P = .027), whereas other dosimetric parameters were similar.

“The toxicity of the whole cohort was very low,” Dr. Meduri summarized. “APBI was associated with a slightly higher rate of late soft tissue and bone toxicity, with a slight decrease in cosmetic outcome at 5 years. But longer follow-up is needed to confirm these results.”

The IRMA findings confirm previous results from the RAPID trial showing that APBI delivered via 3D-conformal radiotherapy may be associated with increased rates of toxicity, Chirag Shah, MD, a radiation oncologist at the Cleveland Clinic in Ohio, said in an interview.

SOURCE: Meduri B et al. ESTRO 2020. Abstract OC-0611.