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Model predicts acute kidney injury in cancer patients a month in advance
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.
FROM AACR: AI, DIAGNOSIS, AND IMAGING 2021
First mammography guidelines for older breast cancer survivors
For women who have a life expectancy of 5-10 years, the guidelines recommend that consideration be given to discontinuing mammography.
Overall, the guidelines encourage shared decision-making that is individualized for each woman after weighing the benefits and harms associated with surveillance mammography and patient preferences.
The panel also recommended that patients with clinical findings and symptoms receive ongoing clinical breast examinations and diagnostic mammography and that patients be reassured that these practices will continue.
Guidelines on breast cancer screening for healthy women already “acknowledge the limitations of mammograms and the need to consider one’s health status and preferences when making decisions on how and when to stop routine mammograms,” said the article’s first author, Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute, Boston.
However, “we don’t have this kind of consensus for women with a history of breast cancer,” she continued. “Current follow-up care guidelines simply state that women with a history of breast cancer with intact breasts should have annual mammography without any guidance.
“In practice, the use of mammograms is highly variable, with less than 50% of breast cancer survivors who have limited life expectancy having annual mammograms, according to survey data we have from prior work,” Dr. Freedman said in an interview.
The guidelines were published online Jan. 28 in JAMA Oncology.
Clinicians discuss how to have these discussions
As part of the process of developing these expert consensus guidelines, the researchers held several clinical focus groups that involved primary care physicians from Brigham and Women’s Hospital and oncology clinicians (including breast surgeons and medical oncologists) from the Dana-Farber Cancer Institute.
All clinicians felt that having expert guidelines and talking points to guide discussions would be helpful, the researchers report.
“However, some oncology clinicians felt that 75 years is often ‘too young’ to stop surveillance mammography and that 80 years may be a more comfortable age to stop routine testing,” they write. “Most clinicians felt that estimations of life expectancy, more than age, should inform the timing of this discussion.”
In contrast to primary and geriatric care clinicians, oncology clinicians reported discomfort with such discussions. They appreciated having the information but “felt it was easier to communicate findings indirectly, without specifically revealing life expectancy to patients. One oncology clinician, however, felt it would be ‘sneaky’ to calculate life expectancy without communicating this to patients, supporting more open discussions,” the authors report.
“All clinicians acknowledged that framing the conversation around patients’ low risk for in-breast cancer events and how mammography will not benefit them was more appealing than discussing life expectancy,” the researchers continue. Their literature review found that the risk of these individuals developing second breast cancers was similar to that of a healthy woman developing a first breast cancer, leading one clinician to comment: “If their risk is really equivalent to the general population – that is very powerful.”
“Some clinicians reported that they ‘focus on the risks’ or frame such discussions by asking: ‘If you were to find something on [a] mammogram, would you do anything about it?’ If a patient answered no, clinicians felt this was a signal to stop mammography,” they noted.
Literature review finds very low risk
Dr. Freedman and colleagues conducted a literature review of the risk for ipsilateral and contralateral breast cancer events among survivors and of the harms and benefits associated with mammography. Following the literature review, a multidisciplinary expert panel, which included patients and patient advocates, was convened to develop consensus guidelines.
The literature review confirmed that there was a low risk for in-breast cancer events in this population and that the risk was particularly low among patients who undergo treatment with endocrine therapy. Among those who did not receive systemic therapy for ERBB2-positive or triple-negative cancers, the rates of ipsilateral recurrence were estimated to be higher.
On the basis of the literature review, the estimated 10-year risk for in-breast cancer events ranged from 1% to 15% for ipsilateral breast cancers and from 1% to 5% for contralateral cancers. Among women in the same age group who did not have a history of breast cancer, the 5-year risk of developing the disease (average risk) was 2.2%.
The authors note that these findings mirror their estimates for new breast cancers among survivors who had low-risk disease. The findings are also similar to those cited in a large-scale mammography study, in which breast cancer survivors aged 70-80 years had a 1.1% annual risk for in-breast cancers. The risk was 0.7%-0.9% for similarly aged patients who did not have a history of breast cancer.
The benefits associated with mammography for older women are not well defined, but the literature suggests that mammography offers little to modest clinical benefit for patients in this age group. The limited benefits are likely because of the more than 10-year time lag that is needed to detect the small improvements in breast cancer mortality; slow-growing tumors generally do not affect the life expectancy of older women, they point out.
“Through our expert consensus process and after iterative feedback from clinicians, we created guidelines to support patients and clinicians in making individualized decisions on how and when to stop mammography,” said Dr. Freedman. “These guidelines are based on the risk of a breast cancer returning in the breast, one’s underlying health, and one’s preferences.”
The guidelines are also intended to provide information to patients on the benefits and harms of mammography in this setting, in addition to “how much we anticipate a mammogram may or may not continue to help a woman over time,” she said.
A companion guide for patients on these guidelines will be published in the coming months.
Dr. Freedman has received institutional clinical trial funding from Eisai and Puma Biotechnology outside the submitted work.
A version of this article first appeared on Medscape.com.
For women who have a life expectancy of 5-10 years, the guidelines recommend that consideration be given to discontinuing mammography.
Overall, the guidelines encourage shared decision-making that is individualized for each woman after weighing the benefits and harms associated with surveillance mammography and patient preferences.
The panel also recommended that patients with clinical findings and symptoms receive ongoing clinical breast examinations and diagnostic mammography and that patients be reassured that these practices will continue.
Guidelines on breast cancer screening for healthy women already “acknowledge the limitations of mammograms and the need to consider one’s health status and preferences when making decisions on how and when to stop routine mammograms,” said the article’s first author, Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute, Boston.
However, “we don’t have this kind of consensus for women with a history of breast cancer,” she continued. “Current follow-up care guidelines simply state that women with a history of breast cancer with intact breasts should have annual mammography without any guidance.
“In practice, the use of mammograms is highly variable, with less than 50% of breast cancer survivors who have limited life expectancy having annual mammograms, according to survey data we have from prior work,” Dr. Freedman said in an interview.
The guidelines were published online Jan. 28 in JAMA Oncology.
Clinicians discuss how to have these discussions
As part of the process of developing these expert consensus guidelines, the researchers held several clinical focus groups that involved primary care physicians from Brigham and Women’s Hospital and oncology clinicians (including breast surgeons and medical oncologists) from the Dana-Farber Cancer Institute.
All clinicians felt that having expert guidelines and talking points to guide discussions would be helpful, the researchers report.
“However, some oncology clinicians felt that 75 years is often ‘too young’ to stop surveillance mammography and that 80 years may be a more comfortable age to stop routine testing,” they write. “Most clinicians felt that estimations of life expectancy, more than age, should inform the timing of this discussion.”
In contrast to primary and geriatric care clinicians, oncology clinicians reported discomfort with such discussions. They appreciated having the information but “felt it was easier to communicate findings indirectly, without specifically revealing life expectancy to patients. One oncology clinician, however, felt it would be ‘sneaky’ to calculate life expectancy without communicating this to patients, supporting more open discussions,” the authors report.
“All clinicians acknowledged that framing the conversation around patients’ low risk for in-breast cancer events and how mammography will not benefit them was more appealing than discussing life expectancy,” the researchers continue. Their literature review found that the risk of these individuals developing second breast cancers was similar to that of a healthy woman developing a first breast cancer, leading one clinician to comment: “If their risk is really equivalent to the general population – that is very powerful.”
“Some clinicians reported that they ‘focus on the risks’ or frame such discussions by asking: ‘If you were to find something on [a] mammogram, would you do anything about it?’ If a patient answered no, clinicians felt this was a signal to stop mammography,” they noted.
Literature review finds very low risk
Dr. Freedman and colleagues conducted a literature review of the risk for ipsilateral and contralateral breast cancer events among survivors and of the harms and benefits associated with mammography. Following the literature review, a multidisciplinary expert panel, which included patients and patient advocates, was convened to develop consensus guidelines.
The literature review confirmed that there was a low risk for in-breast cancer events in this population and that the risk was particularly low among patients who undergo treatment with endocrine therapy. Among those who did not receive systemic therapy for ERBB2-positive or triple-negative cancers, the rates of ipsilateral recurrence were estimated to be higher.
On the basis of the literature review, the estimated 10-year risk for in-breast cancer events ranged from 1% to 15% for ipsilateral breast cancers and from 1% to 5% for contralateral cancers. Among women in the same age group who did not have a history of breast cancer, the 5-year risk of developing the disease (average risk) was 2.2%.
The authors note that these findings mirror their estimates for new breast cancers among survivors who had low-risk disease. The findings are also similar to those cited in a large-scale mammography study, in which breast cancer survivors aged 70-80 years had a 1.1% annual risk for in-breast cancers. The risk was 0.7%-0.9% for similarly aged patients who did not have a history of breast cancer.
The benefits associated with mammography for older women are not well defined, but the literature suggests that mammography offers little to modest clinical benefit for patients in this age group. The limited benefits are likely because of the more than 10-year time lag that is needed to detect the small improvements in breast cancer mortality; slow-growing tumors generally do not affect the life expectancy of older women, they point out.
“Through our expert consensus process and after iterative feedback from clinicians, we created guidelines to support patients and clinicians in making individualized decisions on how and when to stop mammography,” said Dr. Freedman. “These guidelines are based on the risk of a breast cancer returning in the breast, one’s underlying health, and one’s preferences.”
The guidelines are also intended to provide information to patients on the benefits and harms of mammography in this setting, in addition to “how much we anticipate a mammogram may or may not continue to help a woman over time,” she said.
A companion guide for patients on these guidelines will be published in the coming months.
Dr. Freedman has received institutional clinical trial funding from Eisai and Puma Biotechnology outside the submitted work.
A version of this article first appeared on Medscape.com.
For women who have a life expectancy of 5-10 years, the guidelines recommend that consideration be given to discontinuing mammography.
Overall, the guidelines encourage shared decision-making that is individualized for each woman after weighing the benefits and harms associated with surveillance mammography and patient preferences.
The panel also recommended that patients with clinical findings and symptoms receive ongoing clinical breast examinations and diagnostic mammography and that patients be reassured that these practices will continue.
Guidelines on breast cancer screening for healthy women already “acknowledge the limitations of mammograms and the need to consider one’s health status and preferences when making decisions on how and when to stop routine mammograms,” said the article’s first author, Rachel A. Freedman, MD, MPH, of the Dana-Farber Cancer Institute, Boston.
However, “we don’t have this kind of consensus for women with a history of breast cancer,” she continued. “Current follow-up care guidelines simply state that women with a history of breast cancer with intact breasts should have annual mammography without any guidance.
“In practice, the use of mammograms is highly variable, with less than 50% of breast cancer survivors who have limited life expectancy having annual mammograms, according to survey data we have from prior work,” Dr. Freedman said in an interview.
The guidelines were published online Jan. 28 in JAMA Oncology.
Clinicians discuss how to have these discussions
As part of the process of developing these expert consensus guidelines, the researchers held several clinical focus groups that involved primary care physicians from Brigham and Women’s Hospital and oncology clinicians (including breast surgeons and medical oncologists) from the Dana-Farber Cancer Institute.
All clinicians felt that having expert guidelines and talking points to guide discussions would be helpful, the researchers report.
“However, some oncology clinicians felt that 75 years is often ‘too young’ to stop surveillance mammography and that 80 years may be a more comfortable age to stop routine testing,” they write. “Most clinicians felt that estimations of life expectancy, more than age, should inform the timing of this discussion.”
In contrast to primary and geriatric care clinicians, oncology clinicians reported discomfort with such discussions. They appreciated having the information but “felt it was easier to communicate findings indirectly, without specifically revealing life expectancy to patients. One oncology clinician, however, felt it would be ‘sneaky’ to calculate life expectancy without communicating this to patients, supporting more open discussions,” the authors report.
“All clinicians acknowledged that framing the conversation around patients’ low risk for in-breast cancer events and how mammography will not benefit them was more appealing than discussing life expectancy,” the researchers continue. Their literature review found that the risk of these individuals developing second breast cancers was similar to that of a healthy woman developing a first breast cancer, leading one clinician to comment: “If their risk is really equivalent to the general population – that is very powerful.”
“Some clinicians reported that they ‘focus on the risks’ or frame such discussions by asking: ‘If you were to find something on [a] mammogram, would you do anything about it?’ If a patient answered no, clinicians felt this was a signal to stop mammography,” they noted.
Literature review finds very low risk
Dr. Freedman and colleagues conducted a literature review of the risk for ipsilateral and contralateral breast cancer events among survivors and of the harms and benefits associated with mammography. Following the literature review, a multidisciplinary expert panel, which included patients and patient advocates, was convened to develop consensus guidelines.
The literature review confirmed that there was a low risk for in-breast cancer events in this population and that the risk was particularly low among patients who undergo treatment with endocrine therapy. Among those who did not receive systemic therapy for ERBB2-positive or triple-negative cancers, the rates of ipsilateral recurrence were estimated to be higher.
On the basis of the literature review, the estimated 10-year risk for in-breast cancer events ranged from 1% to 15% for ipsilateral breast cancers and from 1% to 5% for contralateral cancers. Among women in the same age group who did not have a history of breast cancer, the 5-year risk of developing the disease (average risk) was 2.2%.
The authors note that these findings mirror their estimates for new breast cancers among survivors who had low-risk disease. The findings are also similar to those cited in a large-scale mammography study, in which breast cancer survivors aged 70-80 years had a 1.1% annual risk for in-breast cancers. The risk was 0.7%-0.9% for similarly aged patients who did not have a history of breast cancer.
The benefits associated with mammography for older women are not well defined, but the literature suggests that mammography offers little to modest clinical benefit for patients in this age group. The limited benefits are likely because of the more than 10-year time lag that is needed to detect the small improvements in breast cancer mortality; slow-growing tumors generally do not affect the life expectancy of older women, they point out.
“Through our expert consensus process and after iterative feedback from clinicians, we created guidelines to support patients and clinicians in making individualized decisions on how and when to stop mammography,” said Dr. Freedman. “These guidelines are based on the risk of a breast cancer returning in the breast, one’s underlying health, and one’s preferences.”
The guidelines are also intended to provide information to patients on the benefits and harms of mammography in this setting, in addition to “how much we anticipate a mammogram may or may not continue to help a woman over time,” she said.
A companion guide for patients on these guidelines will be published in the coming months.
Dr. Freedman has received institutional clinical trial funding from Eisai and Puma Biotechnology outside the submitted work.
A version of this article first appeared on Medscape.com.
The jury’s still out on trifluridine/tipiracil plus bevacizumab in mCRC
The median progression-free survival (PFS) in the phase 2 trial showed a difference of 1.41 months favoring TT-B over C-B, but this difference was not statistically significant.
The median overall survival was 4.64 months longer with TT-B than with C-B. However, the final analysis of TASCO1 was not designed to be comparative for overall survival, “so no formal statistical analysis is presented, and survival is a secondary endpoint,” noted investigator Eric Van Cutsem, MD, PhD, of University Hospital Gasthuisberg in Leuven, Belgium.
Dr. Van Cutsem presented the final results of TASCO1 at the 2021 Gastrointestinal Cancers Symposium (abstract 14).
Prior results from the trial were reported last year (Ann Oncol. 2020 Sep;31[9]:1160-68).
About trifluridine/tipiracil
Trifluridine/tipiracil is an oral drug combining the thymidine analogue trifluridine with tipiracil, an inhibitor of trifluridine degradation. The drug was approved by the Food and Drug Administration in 2015 under the trade name Lonsurf for the treatment of refractory metastatic colorectal cancer, and in 2019 for patients with metastatic gastric cancer or gastroesophageal junction cancer that had been treated with at least two lines of chemotherapy.
Trifluridine/tipiracil was associated with a brief but statistically significant survival benefit when compared with placebo in patients with heavily pretreated metastatic gastric cancer in the TAS-102 Gastric Study (Lancet Oncol. 2018 Nov;19[11]:1437-48).
In a separate analysis of the study, trifluridine/tipiracil was associated with significantly better overall survival and PFS than placebo in patients who had undergone gastrectomy (JAMA Oncol. 2019 Oct 10;6[1]:e193531).
TASCO1 details
In TASCO1, investigators enrolled patients with colorectal cancer who had never received systemic therapy for unresectable metastatic disease, and who were judged to be ineligible for intensive therapy due to advanced age, low tumor burden, poor performance status, comorbidities, or other clinical reasons.
After stratification by RAS status, performance status, and region, patients were randomly assigned to receive TT-B (n = 77) or C-B (n = 76).
TT-B consisted of oral trifluridine/tipiracil at 35 mg/m2 twice daily on days 1-5 and 8-12 every 4 weeks plus bevacizumab at 5 mg/kg intravenously on days 1 and 15 every 4 weeks.
C-B consisted of oral capecitabine at 1,250 or 1,000 mg/m2 twice a day on days 1-14 every 3 weeks plus bevacizumab at 7.5 mg/kg IV on day 1 every 3 weeks.
Final results
The median PFS, the primary endpoint, was 9.23 months with TT-B and 7.82 months with C-B. The difference was not statistically significant, with the upper limit of the 95% confidence interval crossing 1.
The median overall survival was 22.31 months with TT-B and 17.67 months with C-B (hazard ratio, 0.78; 95% CI, 0.55-1.10).
Dr. Van Cutsem pointed out that more patients in the TT-B arm had subsequent therapies compared with patients in the C-B arm – 59.7% vs. 40.8%.
He also noted that the safety profile of TT-B “remains unchanged from the initial analysis.”
Grade 3 or greater neutropenia, decreased neutrophil count, anemia, and decreased white blood cell count were all higher among patients on TT-B, but grade 3 or greater febrile neutropenia was similar between the groups.
Patients in the TT-B arm had more frequent grade 3 or greater nausea, vomiting, and hypertension. Grade 3 or higher hand-foot syndrome and diarrhea were both more common with C-B.
At the study cutoff date in September 2020, 66 patients in each arm had died.
Dr. Van Cutsem said more data on the efficacy of TT-B vs. C-B will come from the ongoing phase 3 SOLSTICE trial. Results from this trial are expected in late 2022.
‘The jury is still out’
The final results from TASCO1 suggest there may be some benefit from TT-B in patients with treatment-naive metastatic colorectal cancer, “but we don’t use it in the first line,” said Jeffery Clark, MD, an oncologist who was not involved in the study.
The trial supports the benefit of combining trifluridine/tipiracil with bevacizumab, and the results were “somewhat better” than he had expected, said Dr. Clark, director of clinical trials support at Mass General Cancer Center in Boston.
“Even though the results are encouraging, there were a couple of things about the trial that one has to at least think about,” Dr. Clark said in an interview.
He noted, for example, that a higher proportion of patients assigned to TT-B had prior adjuvant therapy (27.3% vs. 19.7%), and patients in the TT-B arm were also more likely to have second lines of systemic therapy, which could have skewed the results in favor of the experimental arm.
“I think, basically, the jury is still out until we see the results of the SOLSTICE trial,” he said.
The TASCO1 study was funded by Servier and Taiho. Dr. Van Cutsem has received research funding and served on an advisory board for Servier and other companies. Dr. Clark reported no relevant disclosures.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
The median progression-free survival (PFS) in the phase 2 trial showed a difference of 1.41 months favoring TT-B over C-B, but this difference was not statistically significant.
The median overall survival was 4.64 months longer with TT-B than with C-B. However, the final analysis of TASCO1 was not designed to be comparative for overall survival, “so no formal statistical analysis is presented, and survival is a secondary endpoint,” noted investigator Eric Van Cutsem, MD, PhD, of University Hospital Gasthuisberg in Leuven, Belgium.
Dr. Van Cutsem presented the final results of TASCO1 at the 2021 Gastrointestinal Cancers Symposium (abstract 14).
Prior results from the trial were reported last year (Ann Oncol. 2020 Sep;31[9]:1160-68).
About trifluridine/tipiracil
Trifluridine/tipiracil is an oral drug combining the thymidine analogue trifluridine with tipiracil, an inhibitor of trifluridine degradation. The drug was approved by the Food and Drug Administration in 2015 under the trade name Lonsurf for the treatment of refractory metastatic colorectal cancer, and in 2019 for patients with metastatic gastric cancer or gastroesophageal junction cancer that had been treated with at least two lines of chemotherapy.
Trifluridine/tipiracil was associated with a brief but statistically significant survival benefit when compared with placebo in patients with heavily pretreated metastatic gastric cancer in the TAS-102 Gastric Study (Lancet Oncol. 2018 Nov;19[11]:1437-48).
In a separate analysis of the study, trifluridine/tipiracil was associated with significantly better overall survival and PFS than placebo in patients who had undergone gastrectomy (JAMA Oncol. 2019 Oct 10;6[1]:e193531).
TASCO1 details
In TASCO1, investigators enrolled patients with colorectal cancer who had never received systemic therapy for unresectable metastatic disease, and who were judged to be ineligible for intensive therapy due to advanced age, low tumor burden, poor performance status, comorbidities, or other clinical reasons.
After stratification by RAS status, performance status, and region, patients were randomly assigned to receive TT-B (n = 77) or C-B (n = 76).
TT-B consisted of oral trifluridine/tipiracil at 35 mg/m2 twice daily on days 1-5 and 8-12 every 4 weeks plus bevacizumab at 5 mg/kg intravenously on days 1 and 15 every 4 weeks.
C-B consisted of oral capecitabine at 1,250 or 1,000 mg/m2 twice a day on days 1-14 every 3 weeks plus bevacizumab at 7.5 mg/kg IV on day 1 every 3 weeks.
Final results
The median PFS, the primary endpoint, was 9.23 months with TT-B and 7.82 months with C-B. The difference was not statistically significant, with the upper limit of the 95% confidence interval crossing 1.
The median overall survival was 22.31 months with TT-B and 17.67 months with C-B (hazard ratio, 0.78; 95% CI, 0.55-1.10).
Dr. Van Cutsem pointed out that more patients in the TT-B arm had subsequent therapies compared with patients in the C-B arm – 59.7% vs. 40.8%.
He also noted that the safety profile of TT-B “remains unchanged from the initial analysis.”
Grade 3 or greater neutropenia, decreased neutrophil count, anemia, and decreased white blood cell count were all higher among patients on TT-B, but grade 3 or greater febrile neutropenia was similar between the groups.
Patients in the TT-B arm had more frequent grade 3 or greater nausea, vomiting, and hypertension. Grade 3 or higher hand-foot syndrome and diarrhea were both more common with C-B.
At the study cutoff date in September 2020, 66 patients in each arm had died.
Dr. Van Cutsem said more data on the efficacy of TT-B vs. C-B will come from the ongoing phase 3 SOLSTICE trial. Results from this trial are expected in late 2022.
‘The jury is still out’
The final results from TASCO1 suggest there may be some benefit from TT-B in patients with treatment-naive metastatic colorectal cancer, “but we don’t use it in the first line,” said Jeffery Clark, MD, an oncologist who was not involved in the study.
The trial supports the benefit of combining trifluridine/tipiracil with bevacizumab, and the results were “somewhat better” than he had expected, said Dr. Clark, director of clinical trials support at Mass General Cancer Center in Boston.
“Even though the results are encouraging, there were a couple of things about the trial that one has to at least think about,” Dr. Clark said in an interview.
He noted, for example, that a higher proportion of patients assigned to TT-B had prior adjuvant therapy (27.3% vs. 19.7%), and patients in the TT-B arm were also more likely to have second lines of systemic therapy, which could have skewed the results in favor of the experimental arm.
“I think, basically, the jury is still out until we see the results of the SOLSTICE trial,” he said.
The TASCO1 study was funded by Servier and Taiho. Dr. Van Cutsem has received research funding and served on an advisory board for Servier and other companies. Dr. Clark reported no relevant disclosures.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
The median progression-free survival (PFS) in the phase 2 trial showed a difference of 1.41 months favoring TT-B over C-B, but this difference was not statistically significant.
The median overall survival was 4.64 months longer with TT-B than with C-B. However, the final analysis of TASCO1 was not designed to be comparative for overall survival, “so no formal statistical analysis is presented, and survival is a secondary endpoint,” noted investigator Eric Van Cutsem, MD, PhD, of University Hospital Gasthuisberg in Leuven, Belgium.
Dr. Van Cutsem presented the final results of TASCO1 at the 2021 Gastrointestinal Cancers Symposium (abstract 14).
Prior results from the trial were reported last year (Ann Oncol. 2020 Sep;31[9]:1160-68).
About trifluridine/tipiracil
Trifluridine/tipiracil is an oral drug combining the thymidine analogue trifluridine with tipiracil, an inhibitor of trifluridine degradation. The drug was approved by the Food and Drug Administration in 2015 under the trade name Lonsurf for the treatment of refractory metastatic colorectal cancer, and in 2019 for patients with metastatic gastric cancer or gastroesophageal junction cancer that had been treated with at least two lines of chemotherapy.
Trifluridine/tipiracil was associated with a brief but statistically significant survival benefit when compared with placebo in patients with heavily pretreated metastatic gastric cancer in the TAS-102 Gastric Study (Lancet Oncol. 2018 Nov;19[11]:1437-48).
In a separate analysis of the study, trifluridine/tipiracil was associated with significantly better overall survival and PFS than placebo in patients who had undergone gastrectomy (JAMA Oncol. 2019 Oct 10;6[1]:e193531).
TASCO1 details
In TASCO1, investigators enrolled patients with colorectal cancer who had never received systemic therapy for unresectable metastatic disease, and who were judged to be ineligible for intensive therapy due to advanced age, low tumor burden, poor performance status, comorbidities, or other clinical reasons.
After stratification by RAS status, performance status, and region, patients were randomly assigned to receive TT-B (n = 77) or C-B (n = 76).
TT-B consisted of oral trifluridine/tipiracil at 35 mg/m2 twice daily on days 1-5 and 8-12 every 4 weeks plus bevacizumab at 5 mg/kg intravenously on days 1 and 15 every 4 weeks.
C-B consisted of oral capecitabine at 1,250 or 1,000 mg/m2 twice a day on days 1-14 every 3 weeks plus bevacizumab at 7.5 mg/kg IV on day 1 every 3 weeks.
Final results
The median PFS, the primary endpoint, was 9.23 months with TT-B and 7.82 months with C-B. The difference was not statistically significant, with the upper limit of the 95% confidence interval crossing 1.
The median overall survival was 22.31 months with TT-B and 17.67 months with C-B (hazard ratio, 0.78; 95% CI, 0.55-1.10).
Dr. Van Cutsem pointed out that more patients in the TT-B arm had subsequent therapies compared with patients in the C-B arm – 59.7% vs. 40.8%.
He also noted that the safety profile of TT-B “remains unchanged from the initial analysis.”
Grade 3 or greater neutropenia, decreased neutrophil count, anemia, and decreased white blood cell count were all higher among patients on TT-B, but grade 3 or greater febrile neutropenia was similar between the groups.
Patients in the TT-B arm had more frequent grade 3 or greater nausea, vomiting, and hypertension. Grade 3 or higher hand-foot syndrome and diarrhea were both more common with C-B.
At the study cutoff date in September 2020, 66 patients in each arm had died.
Dr. Van Cutsem said more data on the efficacy of TT-B vs. C-B will come from the ongoing phase 3 SOLSTICE trial. Results from this trial are expected in late 2022.
‘The jury is still out’
The final results from TASCO1 suggest there may be some benefit from TT-B in patients with treatment-naive metastatic colorectal cancer, “but we don’t use it in the first line,” said Jeffery Clark, MD, an oncologist who was not involved in the study.
The trial supports the benefit of combining trifluridine/tipiracil with bevacizumab, and the results were “somewhat better” than he had expected, said Dr. Clark, director of clinical trials support at Mass General Cancer Center in Boston.
“Even though the results are encouraging, there were a couple of things about the trial that one has to at least think about,” Dr. Clark said in an interview.
He noted, for example, that a higher proportion of patients assigned to TT-B had prior adjuvant therapy (27.3% vs. 19.7%), and patients in the TT-B arm were also more likely to have second lines of systemic therapy, which could have skewed the results in favor of the experimental arm.
“I think, basically, the jury is still out until we see the results of the SOLSTICE trial,” he said.
The TASCO1 study was funded by Servier and Taiho. Dr. Van Cutsem has received research funding and served on an advisory board for Servier and other companies. Dr. Clark reported no relevant disclosures.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
FROM GI CANCERS SYMPOSIUM 2021
Combo testing improves CRC screening participation, but not advanced disease detection
Offering a combination of colonoscopy and fecal immunochemical testing (FIT), either in sequence or by choice, may significantly increase participation in colorectal cancer (CRC) screening, according to a prospective study involving more than 12,000 individuals in Poland.
Still, greater participation did not lead to significantly higher rates of advanced disease detection, reported lead author Nastazja Dagny Pilonis, MD, of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, and colleagues in Gastroenterology.
According to the investigators, screening programs that offer colonoscopy and FIT are more effective than those that offer colonoscopy alone, but an optimal combination protocol has yet to be established, and some parts of the world still rely upon a single diagnostic method.
“In Europe, CRC screening programs often implement only one screening modality: colonoscopy, sigmoidoscopy, or stool testing, depending on the health care provider,” the investigators wrote in Gastroenterology. They noted, however, that national guidelines in the United States recommend strategies that include more than one screening method. “‘One-size-fits-all’ approaches to CRC screening do not result in satisfactory participation” because of behavioral, cultural, and socioeconomic variation among individuals.
To improve understanding of the best ways to improve participation, the investigators conducted a prospective randomized trial, PICCOLINO, via the Polish Colonoscopy Screening Program. In total, 12,485 eligible individuals aged between 55 and 64 years received postal invitations to participate in CRC screening. Individuals were randomized in a 1:1:1 ratio into one of three mailing protocols, each of which involved an initial invitation, and, if needed, a second invitation that offered the following:
- Control group: colonoscopy, with nonresponders receiving the same invitation again
- Sequential group: colonoscopy, with nonresponders or refusers receiving a second invitation that offered FIT
- Choice group: choice between colonoscopy or FIT, with nonresponders receiving the same invitation again
The primary outcome was participation in screening within 18 weeks of enrollment. The secondary outcome was diagnostic yield for either advanced adenoma or CRC.
Out of the three groups, the control group had the lowest participation rate, at 17.5%, compared with 25.8% for the sequential group and 26.5% for the choice group. Multivariable logistic regression showed that individuals in the sequential and choice groups had 64% and 70% higher rates of participation, respectively. Across all groups, age of 60 years or older predicted 12% higher likelihood of participation; in contrast, location more than 40 kilometers from a testing center was associated with an 18% decrease in participation, compared with individuals who lived less than 20 kilometers away.
While the control and sequential groups had similar rates of colonoscopy participation, at 17.5% and 15.9%, respectively (P = .788), this rate was significantly lower, at 8.5%, in the choice group (P = .001). Conversely, the sequential group had a significantly lower rate of FITs than the choice group, at 9.9% versus 17.9%, respectively (P = .001). Among participants with a positive FIT, diagnostic work-up colonoscopies were performed in 70.0% of those in the sequential group and 73.3% in the choice group, “despite active call-recall efforts.”
Across all invited individuals, advanced disease detection rates were similar across groups, at 1.1% for both the control and the sequential group and 1.2% for the choice group. Among those who were actually screened, the control group had a slightly higher diagnostic yield for advanced neoplasia, at 6.5%, compared with 4.2% in the sequential group and 4.4% in the choice group; however, these differences were not statistically significant. In contrast, significantly more adenomas of any kind were detected in the control and sequential groups (5.6% for both) than the choice group (3.9%) (P < .001).
“Although the strategies which included FIT showed higher participation rates than the strategy of offering colonoscopy alone, these strategies did not result in increased detection rates of advanced neoplasia in the intention to screen analysis,” the investigators wrote. “An absolute increase in participation rates of 8%-10% seems insufficient to translate into higher advanced neoplasia detection at the population level.”
Dr. Pilonis and colleagues also suggested that the relatively low rate of diagnostic colonoscopy after positive FIT contributed to the suboptimal diagnostic yield.
“These rates are unsatisfactory taking into account significant call-recall efforts, but are within the range reported in other studies,” they wrote.
They also wrote that their study compared participation and detection between one-time colonoscopy and one-time screening strategies combining colonoscopy and FIT. In acknowledging this, they noted that these approaches have different screening intervals and uptake over time: “FIT has been shown to achieve higher participation rates than colonoscopy for one time screening, but its uptake over several rounds may not be superior to one time colonoscopy.” Furthermore, detection rates of the sequential or choice strategies for advanced disease may rise over time with further implementation, so the one-time screening may not be sufficient to reveal what could become significant differences.
The study was funded by the Polish Ministry of Health, the Polish Foundation of Gastroenterology, and the Centre of Postgraduate Medical Education in Warsaw. FITs, materials, and reagents were provided by Eiken Chemical. The investigators disclosed relationships with Boston Scientific, AbbVie, Olympus, and others.
Offering a combination of colonoscopy and fecal immunochemical testing (FIT), either in sequence or by choice, may significantly increase participation in colorectal cancer (CRC) screening, according to a prospective study involving more than 12,000 individuals in Poland.
Still, greater participation did not lead to significantly higher rates of advanced disease detection, reported lead author Nastazja Dagny Pilonis, MD, of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, and colleagues in Gastroenterology.
According to the investigators, screening programs that offer colonoscopy and FIT are more effective than those that offer colonoscopy alone, but an optimal combination protocol has yet to be established, and some parts of the world still rely upon a single diagnostic method.
“In Europe, CRC screening programs often implement only one screening modality: colonoscopy, sigmoidoscopy, or stool testing, depending on the health care provider,” the investigators wrote in Gastroenterology. They noted, however, that national guidelines in the United States recommend strategies that include more than one screening method. “‘One-size-fits-all’ approaches to CRC screening do not result in satisfactory participation” because of behavioral, cultural, and socioeconomic variation among individuals.
To improve understanding of the best ways to improve participation, the investigators conducted a prospective randomized trial, PICCOLINO, via the Polish Colonoscopy Screening Program. In total, 12,485 eligible individuals aged between 55 and 64 years received postal invitations to participate in CRC screening. Individuals were randomized in a 1:1:1 ratio into one of three mailing protocols, each of which involved an initial invitation, and, if needed, a second invitation that offered the following:
- Control group: colonoscopy, with nonresponders receiving the same invitation again
- Sequential group: colonoscopy, with nonresponders or refusers receiving a second invitation that offered FIT
- Choice group: choice between colonoscopy or FIT, with nonresponders receiving the same invitation again
The primary outcome was participation in screening within 18 weeks of enrollment. The secondary outcome was diagnostic yield for either advanced adenoma or CRC.
Out of the three groups, the control group had the lowest participation rate, at 17.5%, compared with 25.8% for the sequential group and 26.5% for the choice group. Multivariable logistic regression showed that individuals in the sequential and choice groups had 64% and 70% higher rates of participation, respectively. Across all groups, age of 60 years or older predicted 12% higher likelihood of participation; in contrast, location more than 40 kilometers from a testing center was associated with an 18% decrease in participation, compared with individuals who lived less than 20 kilometers away.
While the control and sequential groups had similar rates of colonoscopy participation, at 17.5% and 15.9%, respectively (P = .788), this rate was significantly lower, at 8.5%, in the choice group (P = .001). Conversely, the sequential group had a significantly lower rate of FITs than the choice group, at 9.9% versus 17.9%, respectively (P = .001). Among participants with a positive FIT, diagnostic work-up colonoscopies were performed in 70.0% of those in the sequential group and 73.3% in the choice group, “despite active call-recall efforts.”
Across all invited individuals, advanced disease detection rates were similar across groups, at 1.1% for both the control and the sequential group and 1.2% for the choice group. Among those who were actually screened, the control group had a slightly higher diagnostic yield for advanced neoplasia, at 6.5%, compared with 4.2% in the sequential group and 4.4% in the choice group; however, these differences were not statistically significant. In contrast, significantly more adenomas of any kind were detected in the control and sequential groups (5.6% for both) than the choice group (3.9%) (P < .001).
“Although the strategies which included FIT showed higher participation rates than the strategy of offering colonoscopy alone, these strategies did not result in increased detection rates of advanced neoplasia in the intention to screen analysis,” the investigators wrote. “An absolute increase in participation rates of 8%-10% seems insufficient to translate into higher advanced neoplasia detection at the population level.”
Dr. Pilonis and colleagues also suggested that the relatively low rate of diagnostic colonoscopy after positive FIT contributed to the suboptimal diagnostic yield.
“These rates are unsatisfactory taking into account significant call-recall efforts, but are within the range reported in other studies,” they wrote.
They also wrote that their study compared participation and detection between one-time colonoscopy and one-time screening strategies combining colonoscopy and FIT. In acknowledging this, they noted that these approaches have different screening intervals and uptake over time: “FIT has been shown to achieve higher participation rates than colonoscopy for one time screening, but its uptake over several rounds may not be superior to one time colonoscopy.” Furthermore, detection rates of the sequential or choice strategies for advanced disease may rise over time with further implementation, so the one-time screening may not be sufficient to reveal what could become significant differences.
The study was funded by the Polish Ministry of Health, the Polish Foundation of Gastroenterology, and the Centre of Postgraduate Medical Education in Warsaw. FITs, materials, and reagents were provided by Eiken Chemical. The investigators disclosed relationships with Boston Scientific, AbbVie, Olympus, and others.
Offering a combination of colonoscopy and fecal immunochemical testing (FIT), either in sequence or by choice, may significantly increase participation in colorectal cancer (CRC) screening, according to a prospective study involving more than 12,000 individuals in Poland.
Still, greater participation did not lead to significantly higher rates of advanced disease detection, reported lead author Nastazja Dagny Pilonis, MD, of the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, and colleagues in Gastroenterology.
According to the investigators, screening programs that offer colonoscopy and FIT are more effective than those that offer colonoscopy alone, but an optimal combination protocol has yet to be established, and some parts of the world still rely upon a single diagnostic method.
“In Europe, CRC screening programs often implement only one screening modality: colonoscopy, sigmoidoscopy, or stool testing, depending on the health care provider,” the investigators wrote in Gastroenterology. They noted, however, that national guidelines in the United States recommend strategies that include more than one screening method. “‘One-size-fits-all’ approaches to CRC screening do not result in satisfactory participation” because of behavioral, cultural, and socioeconomic variation among individuals.
To improve understanding of the best ways to improve participation, the investigators conducted a prospective randomized trial, PICCOLINO, via the Polish Colonoscopy Screening Program. In total, 12,485 eligible individuals aged between 55 and 64 years received postal invitations to participate in CRC screening. Individuals were randomized in a 1:1:1 ratio into one of three mailing protocols, each of which involved an initial invitation, and, if needed, a second invitation that offered the following:
- Control group: colonoscopy, with nonresponders receiving the same invitation again
- Sequential group: colonoscopy, with nonresponders or refusers receiving a second invitation that offered FIT
- Choice group: choice between colonoscopy or FIT, with nonresponders receiving the same invitation again
The primary outcome was participation in screening within 18 weeks of enrollment. The secondary outcome was diagnostic yield for either advanced adenoma or CRC.
Out of the three groups, the control group had the lowest participation rate, at 17.5%, compared with 25.8% for the sequential group and 26.5% for the choice group. Multivariable logistic regression showed that individuals in the sequential and choice groups had 64% and 70% higher rates of participation, respectively. Across all groups, age of 60 years or older predicted 12% higher likelihood of participation; in contrast, location more than 40 kilometers from a testing center was associated with an 18% decrease in participation, compared with individuals who lived less than 20 kilometers away.
While the control and sequential groups had similar rates of colonoscopy participation, at 17.5% and 15.9%, respectively (P = .788), this rate was significantly lower, at 8.5%, in the choice group (P = .001). Conversely, the sequential group had a significantly lower rate of FITs than the choice group, at 9.9% versus 17.9%, respectively (P = .001). Among participants with a positive FIT, diagnostic work-up colonoscopies were performed in 70.0% of those in the sequential group and 73.3% in the choice group, “despite active call-recall efforts.”
Across all invited individuals, advanced disease detection rates were similar across groups, at 1.1% for both the control and the sequential group and 1.2% for the choice group. Among those who were actually screened, the control group had a slightly higher diagnostic yield for advanced neoplasia, at 6.5%, compared with 4.2% in the sequential group and 4.4% in the choice group; however, these differences were not statistically significant. In contrast, significantly more adenomas of any kind were detected in the control and sequential groups (5.6% for both) than the choice group (3.9%) (P < .001).
“Although the strategies which included FIT showed higher participation rates than the strategy of offering colonoscopy alone, these strategies did not result in increased detection rates of advanced neoplasia in the intention to screen analysis,” the investigators wrote. “An absolute increase in participation rates of 8%-10% seems insufficient to translate into higher advanced neoplasia detection at the population level.”
Dr. Pilonis and colleagues also suggested that the relatively low rate of diagnostic colonoscopy after positive FIT contributed to the suboptimal diagnostic yield.
“These rates are unsatisfactory taking into account significant call-recall efforts, but are within the range reported in other studies,” they wrote.
They also wrote that their study compared participation and detection between one-time colonoscopy and one-time screening strategies combining colonoscopy and FIT. In acknowledging this, they noted that these approaches have different screening intervals and uptake over time: “FIT has been shown to achieve higher participation rates than colonoscopy for one time screening, but its uptake over several rounds may not be superior to one time colonoscopy.” Furthermore, detection rates of the sequential or choice strategies for advanced disease may rise over time with further implementation, so the one-time screening may not be sufficient to reveal what could become significant differences.
The study was funded by the Polish Ministry of Health, the Polish Foundation of Gastroenterology, and the Centre of Postgraduate Medical Education in Warsaw. FITs, materials, and reagents were provided by Eiken Chemical. The investigators disclosed relationships with Boston Scientific, AbbVie, Olympus, and others.
FROM GASTROENTEROLOGY
AI can identify biomarkers and potentially guide therapy in NSCLC
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.
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.
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.
FROM AACR: AI, DIAGNOSIS, AND IMAGING 2021
Call for Myeloma, Leukemia, Lymphoma and Other Hematology Papers
Federal Practitioner is inviting VA, DoD, and PHS health care providers and researchers to contribute to a future special issue on hematology topics, including myelomas, lymphomas, leukemias, and other bloodborne dieases.
Interested authors should submit a brief 2 to 3 sentence abstract to [email protected]. Federal Practitioner welcomes case studies, literature reviews, original research, program profiles, guest editorials, and other evidence-based articles. The updated and complete submission guidelines, including details about the style and format, can be found here:
http://www.mdedge.com/fedprac/page/submission-guidelines
Federal Practitioner uses Editorial Manager , a web-based manuscript submission and review system. All manuscripts must be submitted through this system.
All manuscripts submitted to Federal Practitioner for both special and regular issues will be subject to peer review. Peer reviews are conducted in a double-blind fashion, and the reviewers are asked to comment on the manuscript’s importance, accuracy, relevance, clarity, timeliness, balance, and reference citation. Final decisions on all submitted manuscripts are made by the Editor-in-Chief (or, in the event of a potential conflict of interest, a designated surrogate from the journal’s Editorial Advisory Association).
Federal Practitioner is inviting VA, DoD, and PHS health care providers and researchers to contribute to a future special issue on hematology topics, including myelomas, lymphomas, leukemias, and other bloodborne dieases.
Interested authors should submit a brief 2 to 3 sentence abstract to [email protected]. Federal Practitioner welcomes case studies, literature reviews, original research, program profiles, guest editorials, and other evidence-based articles. The updated and complete submission guidelines, including details about the style and format, can be found here:
http://www.mdedge.com/fedprac/page/submission-guidelines
Federal Practitioner uses Editorial Manager , a web-based manuscript submission and review system. All manuscripts must be submitted through this system.
All manuscripts submitted to Federal Practitioner for both special and regular issues will be subject to peer review. Peer reviews are conducted in a double-blind fashion, and the reviewers are asked to comment on the manuscript’s importance, accuracy, relevance, clarity, timeliness, balance, and reference citation. Final decisions on all submitted manuscripts are made by the Editor-in-Chief (or, in the event of a potential conflict of interest, a designated surrogate from the journal’s Editorial Advisory Association).
Federal Practitioner is inviting VA, DoD, and PHS health care providers and researchers to contribute to a future special issue on hematology topics, including myelomas, lymphomas, leukemias, and other bloodborne dieases.
Interested authors should submit a brief 2 to 3 sentence abstract to [email protected]. Federal Practitioner welcomes case studies, literature reviews, original research, program profiles, guest editorials, and other evidence-based articles. The updated and complete submission guidelines, including details about the style and format, can be found here:
http://www.mdedge.com/fedprac/page/submission-guidelines
Federal Practitioner uses Editorial Manager , a web-based manuscript submission and review system. All manuscripts must be submitted through this system.
All manuscripts submitted to Federal Practitioner for both special and regular issues will be subject to peer review. Peer reviews are conducted in a double-blind fashion, and the reviewers are asked to comment on the manuscript’s importance, accuracy, relevance, clarity, timeliness, balance, and reference citation. Final decisions on all submitted manuscripts are made by the Editor-in-Chief (or, in the event of a potential conflict of interest, a designated surrogate from the journal’s Editorial Advisory Association).
Lung disease raises mortality risk in older RA patients
Patients with rheumatoid arthritis–associated interstitial lung disease showed increases in overall mortality, respiratory mortality, and cancer mortality, compared with RA patients without interstitial lung disease, based on data from more than 500,000 patients in a nationwide cohort study.
RA-associated interstitial lung disease (RA-ILD) has been associated with worse survival rates as well as reduced quality of life, functional impairment, and increased health care use and costs, wrote Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on the incidence and prevalence of RA-ILD have been inconsistent and large studies are lacking.
In a study published online in Rheumatology, the researchers identified 509,787 RA patients aged 65 years and older from Medicare claims data. The average age of the patients was 72.6 years, and 76.2% were women.
At baseline, 10,306 (2%) of the study population had RA-ILD, and 13,372 (2.7%) developed RA-ILD over an average of 3.8 years’ follow-up per person (total of 1,873,127 person-years of follow-up). The overall incidence of RA-ILD was 7.14 per 1,000 person-years.
Overall mortality was significantly higher among RA-ILD patients than in those with RA alone in a multivariate analysis (38.7% vs. 20.7%; hazard ratio, 1.66).
In addition, RA-ILD was associated with an increased risk of respiratory mortality (HR, 4.39) and cancer mortality (HR, 1.56), compared with RA without ILD. For these hazard regression analyses, the researchers used Fine and Gray subdistribution HRs “to handle competing risks of alternative causes of mortality. For example, the risk of respiratory mortality for patients with RA-ILD, compared with RA without ILD also accounted for the competing risk of cardiovascular, cancer, infection and other types of mortality.”
In another multivariate analysis, male gender, smoking, asthma, chronic obstructive pulmonary disorder, and medication use (specifically biologic disease-modifying antirheumatic drugs, targeted synthetic DMARDs, and glucocorticoids) were independently associated with increased incident RA-ILD at baseline. However, “the associations of RA-related medications with incident RA-ILD risk should be interpreted with caution since they may be explained by unmeasured factors, including RA disease activity, severity, comorbidities, and prior or concomitant medication use,” the researchers noted.
The study findings were limited by several factors, including the lack of data on disease activity, disease duration, disease severity, and RA-related autoantibodies, the researchers noted. However, the results support data from previous studies and were strengthened by the large sample size and data on demographics and health care use.
“Ours is the first to study the epidemiology and mortality outcomes of RA-ILD using a validated claims algorithm to identify RA and RA-ILD,” and “to quantify the mortality burden of RA-ILD and to identify a potentially novel association of RA-ILD with cancer mortality,” they noted.
The study was supported by an investigator-initiated grant from Bristol-Myers Squibb. Lead author Dr. Sparks disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. Dr. Sparks also disclosed serving as a consultant to Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer for work unrelated to the current study. Other authors reported research funding from Bristol-Myers Squibb, involvement in a clinical trial funded by Genentech and Bristol-Myers Squibb, and receiving research support to Brigham and Women’s Hospital for other studies from AbbVie, Bayer, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Vertex.
Patients with rheumatoid arthritis–associated interstitial lung disease showed increases in overall mortality, respiratory mortality, and cancer mortality, compared with RA patients without interstitial lung disease, based on data from more than 500,000 patients in a nationwide cohort study.
RA-associated interstitial lung disease (RA-ILD) has been associated with worse survival rates as well as reduced quality of life, functional impairment, and increased health care use and costs, wrote Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on the incidence and prevalence of RA-ILD have been inconsistent and large studies are lacking.
In a study published online in Rheumatology, the researchers identified 509,787 RA patients aged 65 years and older from Medicare claims data. The average age of the patients was 72.6 years, and 76.2% were women.
At baseline, 10,306 (2%) of the study population had RA-ILD, and 13,372 (2.7%) developed RA-ILD over an average of 3.8 years’ follow-up per person (total of 1,873,127 person-years of follow-up). The overall incidence of RA-ILD was 7.14 per 1,000 person-years.
Overall mortality was significantly higher among RA-ILD patients than in those with RA alone in a multivariate analysis (38.7% vs. 20.7%; hazard ratio, 1.66).
In addition, RA-ILD was associated with an increased risk of respiratory mortality (HR, 4.39) and cancer mortality (HR, 1.56), compared with RA without ILD. For these hazard regression analyses, the researchers used Fine and Gray subdistribution HRs “to handle competing risks of alternative causes of mortality. For example, the risk of respiratory mortality for patients with RA-ILD, compared with RA without ILD also accounted for the competing risk of cardiovascular, cancer, infection and other types of mortality.”
In another multivariate analysis, male gender, smoking, asthma, chronic obstructive pulmonary disorder, and medication use (specifically biologic disease-modifying antirheumatic drugs, targeted synthetic DMARDs, and glucocorticoids) were independently associated with increased incident RA-ILD at baseline. However, “the associations of RA-related medications with incident RA-ILD risk should be interpreted with caution since they may be explained by unmeasured factors, including RA disease activity, severity, comorbidities, and prior or concomitant medication use,” the researchers noted.
The study findings were limited by several factors, including the lack of data on disease activity, disease duration, disease severity, and RA-related autoantibodies, the researchers noted. However, the results support data from previous studies and were strengthened by the large sample size and data on demographics and health care use.
“Ours is the first to study the epidemiology and mortality outcomes of RA-ILD using a validated claims algorithm to identify RA and RA-ILD,” and “to quantify the mortality burden of RA-ILD and to identify a potentially novel association of RA-ILD with cancer mortality,” they noted.
The study was supported by an investigator-initiated grant from Bristol-Myers Squibb. Lead author Dr. Sparks disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. Dr. Sparks also disclosed serving as a consultant to Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer for work unrelated to the current study. Other authors reported research funding from Bristol-Myers Squibb, involvement in a clinical trial funded by Genentech and Bristol-Myers Squibb, and receiving research support to Brigham and Women’s Hospital for other studies from AbbVie, Bayer, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Vertex.
Patients with rheumatoid arthritis–associated interstitial lung disease showed increases in overall mortality, respiratory mortality, and cancer mortality, compared with RA patients without interstitial lung disease, based on data from more than 500,000 patients in a nationwide cohort study.
RA-associated interstitial lung disease (RA-ILD) has been associated with worse survival rates as well as reduced quality of life, functional impairment, and increased health care use and costs, wrote Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital, Boston, and colleagues. However, data on the incidence and prevalence of RA-ILD have been inconsistent and large studies are lacking.
In a study published online in Rheumatology, the researchers identified 509,787 RA patients aged 65 years and older from Medicare claims data. The average age of the patients was 72.6 years, and 76.2% were women.
At baseline, 10,306 (2%) of the study population had RA-ILD, and 13,372 (2.7%) developed RA-ILD over an average of 3.8 years’ follow-up per person (total of 1,873,127 person-years of follow-up). The overall incidence of RA-ILD was 7.14 per 1,000 person-years.
Overall mortality was significantly higher among RA-ILD patients than in those with RA alone in a multivariate analysis (38.7% vs. 20.7%; hazard ratio, 1.66).
In addition, RA-ILD was associated with an increased risk of respiratory mortality (HR, 4.39) and cancer mortality (HR, 1.56), compared with RA without ILD. For these hazard regression analyses, the researchers used Fine and Gray subdistribution HRs “to handle competing risks of alternative causes of mortality. For example, the risk of respiratory mortality for patients with RA-ILD, compared with RA without ILD also accounted for the competing risk of cardiovascular, cancer, infection and other types of mortality.”
In another multivariate analysis, male gender, smoking, asthma, chronic obstructive pulmonary disorder, and medication use (specifically biologic disease-modifying antirheumatic drugs, targeted synthetic DMARDs, and glucocorticoids) were independently associated with increased incident RA-ILD at baseline. However, “the associations of RA-related medications with incident RA-ILD risk should be interpreted with caution since they may be explained by unmeasured factors, including RA disease activity, severity, comorbidities, and prior or concomitant medication use,” the researchers noted.
The study findings were limited by several factors, including the lack of data on disease activity, disease duration, disease severity, and RA-related autoantibodies, the researchers noted. However, the results support data from previous studies and were strengthened by the large sample size and data on demographics and health care use.
“Ours is the first to study the epidemiology and mortality outcomes of RA-ILD using a validated claims algorithm to identify RA and RA-ILD,” and “to quantify the mortality burden of RA-ILD and to identify a potentially novel association of RA-ILD with cancer mortality,” they noted.
The study was supported by an investigator-initiated grant from Bristol-Myers Squibb. Lead author Dr. Sparks disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. Dr. Sparks also disclosed serving as a consultant to Bristol-Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer for work unrelated to the current study. Other authors reported research funding from Bristol-Myers Squibb, involvement in a clinical trial funded by Genentech and Bristol-Myers Squibb, and receiving research support to Brigham and Women’s Hospital for other studies from AbbVie, Bayer, Bristol-Myers Squibb, Novartis, Pfizer, Roche, and Vertex.
FROM RHEUMATOLOGY
Even patients with cancer in remission at risk for severe COVID-19
It’s been shown that hospitalized cancer patients and those undergoing active treatment are at high risk for severe COVID-19 complications. A new study shows that patients with cancer in remission are at higher risk, too.
For the study, investigators from the University of Pennsylvania, Philadelphia, analyzed 323 patients with SARS-CoV-2 infection in a research database with more than 4,800 patients. About 20% of database patients were Black, but they accounted for almost 65% of the infections, reflecting previous reports of increased risk for COVID among Black people.
A total of 67 of the infected patients had cancer, including 18 patients with active cancer and 49 patients whose cancer was in remission. After adjusting for demographics, smoking status, and comorbidities, a diagnosis of cancer more than doubled the odds of hospitalization and increased the odds of 30-day mortality nearly sixfold.
Worse outcomes were more strongly associated with active cancer, but patients whose cancer was in remission were also at higher risk than patients who did not have cancer.
It’s not only “patients hospitalized or on treatment ... all oncology patients need to take significant precautions during the pandemic to protect themselves,” senior investigator Kara Maxwell, MD, PhD, hematologist/oncologist and assistant professor at the University of Pennsylvania, said in a press release.
The study was published online on Jan. 21 in JNCI Cancer Spectrum.
The good news is that steps to prevent SARS-CoV-2 infection work, suggests a second report from the University of Pennsylvania. Among 124 cancer patients who underwent outpatient infusions from May to October 2020, not a single one experienced seroconversion over a median of 13 clinical visits. That second study was published on Jan. 16 in medRxiv and is pending peer review.
The zero seroconversion rate likely reflects “the success of transmission mitigation measures within health care facilities,” wrote investigators led by Lova Sun, MD, a hematology/oncology fellow at the University of Pennsylvania.
Like many institutions, the University of Pennsylvania Health System (Penn Medicine) is aggressive in protecting outpatients against the virus, the authors wrote. Among other steps, patients are queried about symptoms and contacts before their office visit, and their temperature is taken when they come in. Masks are worn, check-in is contactless, the number of visitors is limited, and patients who test positive are treated in a separate space.
In addition, patients in the study also reported that they wore masks and practiced social distancing in their daily lives.
Approached for comment, hematologist/oncologist Charles Shapiro, MD, a professor at the Icahn School of Medicine at Mount Sinai and director of translational breast cancer research at Mount Sinai Hospital, both in New York, said he wasn’t surprised that the prevention measures followed at Penn Medicine work. They are very similar to the measures followed at Mount Sinai oncology clinics, and “there’ve been very few COVID cases in our shop,” he added.
The bigger take-home message from both studies is that cancer patients, regardless of their age or if they are in remission, should be prioritized for vaccination against COVID-19, which is the best way to mitigate risk. “I strongly urge my patients to get it” if they can, he said.
The problem in New York is that immunizations are largely limited to people aged 65 years and older. Younger cancer patients are left out, and access has been spotty for all patients. “Vaccine is available one day, then not the next. It’s disheartening,” Dr. Shapiro said in an interview. “Hopefully, with the new administration, this will smooth out,” and the age limit will drop.
The study was supported by the National Institutes of Health, among other organizations. Dr. Lova, Dr. Maxwell, and Dr. Shapiro have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
It’s been shown that hospitalized cancer patients and those undergoing active treatment are at high risk for severe COVID-19 complications. A new study shows that patients with cancer in remission are at higher risk, too.
For the study, investigators from the University of Pennsylvania, Philadelphia, analyzed 323 patients with SARS-CoV-2 infection in a research database with more than 4,800 patients. About 20% of database patients were Black, but they accounted for almost 65% of the infections, reflecting previous reports of increased risk for COVID among Black people.
A total of 67 of the infected patients had cancer, including 18 patients with active cancer and 49 patients whose cancer was in remission. After adjusting for demographics, smoking status, and comorbidities, a diagnosis of cancer more than doubled the odds of hospitalization and increased the odds of 30-day mortality nearly sixfold.
Worse outcomes were more strongly associated with active cancer, but patients whose cancer was in remission were also at higher risk than patients who did not have cancer.
It’s not only “patients hospitalized or on treatment ... all oncology patients need to take significant precautions during the pandemic to protect themselves,” senior investigator Kara Maxwell, MD, PhD, hematologist/oncologist and assistant professor at the University of Pennsylvania, said in a press release.
The study was published online on Jan. 21 in JNCI Cancer Spectrum.
The good news is that steps to prevent SARS-CoV-2 infection work, suggests a second report from the University of Pennsylvania. Among 124 cancer patients who underwent outpatient infusions from May to October 2020, not a single one experienced seroconversion over a median of 13 clinical visits. That second study was published on Jan. 16 in medRxiv and is pending peer review.
The zero seroconversion rate likely reflects “the success of transmission mitigation measures within health care facilities,” wrote investigators led by Lova Sun, MD, a hematology/oncology fellow at the University of Pennsylvania.
Like many institutions, the University of Pennsylvania Health System (Penn Medicine) is aggressive in protecting outpatients against the virus, the authors wrote. Among other steps, patients are queried about symptoms and contacts before their office visit, and their temperature is taken when they come in. Masks are worn, check-in is contactless, the number of visitors is limited, and patients who test positive are treated in a separate space.
In addition, patients in the study also reported that they wore masks and practiced social distancing in their daily lives.
Approached for comment, hematologist/oncologist Charles Shapiro, MD, a professor at the Icahn School of Medicine at Mount Sinai and director of translational breast cancer research at Mount Sinai Hospital, both in New York, said he wasn’t surprised that the prevention measures followed at Penn Medicine work. They are very similar to the measures followed at Mount Sinai oncology clinics, and “there’ve been very few COVID cases in our shop,” he added.
The bigger take-home message from both studies is that cancer patients, regardless of their age or if they are in remission, should be prioritized for vaccination against COVID-19, which is the best way to mitigate risk. “I strongly urge my patients to get it” if they can, he said.
The problem in New York is that immunizations are largely limited to people aged 65 years and older. Younger cancer patients are left out, and access has been spotty for all patients. “Vaccine is available one day, then not the next. It’s disheartening,” Dr. Shapiro said in an interview. “Hopefully, with the new administration, this will smooth out,” and the age limit will drop.
The study was supported by the National Institutes of Health, among other organizations. Dr. Lova, Dr. Maxwell, and Dr. Shapiro have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
It’s been shown that hospitalized cancer patients and those undergoing active treatment are at high risk for severe COVID-19 complications. A new study shows that patients with cancer in remission are at higher risk, too.
For the study, investigators from the University of Pennsylvania, Philadelphia, analyzed 323 patients with SARS-CoV-2 infection in a research database with more than 4,800 patients. About 20% of database patients were Black, but they accounted for almost 65% of the infections, reflecting previous reports of increased risk for COVID among Black people.
A total of 67 of the infected patients had cancer, including 18 patients with active cancer and 49 patients whose cancer was in remission. After adjusting for demographics, smoking status, and comorbidities, a diagnosis of cancer more than doubled the odds of hospitalization and increased the odds of 30-day mortality nearly sixfold.
Worse outcomes were more strongly associated with active cancer, but patients whose cancer was in remission were also at higher risk than patients who did not have cancer.
It’s not only “patients hospitalized or on treatment ... all oncology patients need to take significant precautions during the pandemic to protect themselves,” senior investigator Kara Maxwell, MD, PhD, hematologist/oncologist and assistant professor at the University of Pennsylvania, said in a press release.
The study was published online on Jan. 21 in JNCI Cancer Spectrum.
The good news is that steps to prevent SARS-CoV-2 infection work, suggests a second report from the University of Pennsylvania. Among 124 cancer patients who underwent outpatient infusions from May to October 2020, not a single one experienced seroconversion over a median of 13 clinical visits. That second study was published on Jan. 16 in medRxiv and is pending peer review.
The zero seroconversion rate likely reflects “the success of transmission mitigation measures within health care facilities,” wrote investigators led by Lova Sun, MD, a hematology/oncology fellow at the University of Pennsylvania.
Like many institutions, the University of Pennsylvania Health System (Penn Medicine) is aggressive in protecting outpatients against the virus, the authors wrote. Among other steps, patients are queried about symptoms and contacts before their office visit, and their temperature is taken when they come in. Masks are worn, check-in is contactless, the number of visitors is limited, and patients who test positive are treated in a separate space.
In addition, patients in the study also reported that they wore masks and practiced social distancing in their daily lives.
Approached for comment, hematologist/oncologist Charles Shapiro, MD, a professor at the Icahn School of Medicine at Mount Sinai and director of translational breast cancer research at Mount Sinai Hospital, both in New York, said he wasn’t surprised that the prevention measures followed at Penn Medicine work. They are very similar to the measures followed at Mount Sinai oncology clinics, and “there’ve been very few COVID cases in our shop,” he added.
The bigger take-home message from both studies is that cancer patients, regardless of their age or if they are in remission, should be prioritized for vaccination against COVID-19, which is the best way to mitigate risk. “I strongly urge my patients to get it” if they can, he said.
The problem in New York is that immunizations are largely limited to people aged 65 years and older. Younger cancer patients are left out, and access has been spotty for all patients. “Vaccine is available one day, then not the next. It’s disheartening,” Dr. Shapiro said in an interview. “Hopefully, with the new administration, this will smooth out,” and the age limit will drop.
The study was supported by the National Institutes of Health, among other organizations. Dr. Lova, Dr. Maxwell, and Dr. Shapiro have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Triplet shows ‘promising’ activity in unresectable/metastatic CRC
The trial was designed to test the combination of panitumumab, ipilimumab, and nivolumab in patients with previously treated, unresectable and/or metastatic, microsatellite stable or mismatch repair–proficient CRC without mutations in KRAS, NRAS, or BRAF.
Among 49 evaluable patients treated with the triplet, 35% had a partial response at 12 weeks of follow-up, which met the trial’s primary response endpoint, according to investigator Michael S. Lee, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Though toxicities were, of course, observed, they were consistent overall with the expected adverse event profiles of anti-EGFR therapy and combination ipilimumab and nivolumab. Correlative studies are ongoing to identify potential biomarkers of response,” Dr. Lee said when presenting the trial results at the 2021 Gastrointestinal Cancers Symposium (Abstract 7).
Immune activation?
The rationale for adding panitumumab to immune checkpoint inhibitors comes, in part, from a trial published in 2014 in The Lancet Oncology. The trial showed that panitumumab was noninferior to cetuximab. Panitumumab was associated with a 22% response rate in patients with KRAS wild-type, metastatic CRC that was refractory to chemotherapy. Progression-free survival (PFS) and overall survival (OS) were similar between the treatment arms.
In addition, in mouse models of RAS wild-type CRC, treatment with an anti-EGFR antibody induced immunogenic cell death.
“Moreover, translational studies of tumor biopsies from patients who were treated with the anti-EGFR antibody cetuximab showed that responders had significant increases in T-cell infiltration and cytolytic activity within tumors after starting treatment,” Dr. Lee said.
In the latter studies, tumor samples taken at the time of disease progression also showed increased expression of immune checkpoint inhibitor pathways, including PD-L1, the primary target of nivolumab, and CTLA-4, the primary target of ipilimumab.
“Given this, we hypothesized that combining anti–PD-1 and anti–CTLA-4 antibodies with anti-EGFR therapy would be synergistic,” Dr. Lee said.
Single-arm study
Investigators enrolled patients with unresectable and/or metastatic CRC in the trial. All patients had disease that was KRAS, NRAS, and BRAF wild-type, and they had either microsatellite stability or proficient mismatch repair. Patients also had to have received one or two prior lines of therapy, not including an anti-EGFR agent.
The patients received panitumumab at 6 mg/kg IV every 2 weeks, nivolumab at 240 mg IV every 2 weeks, and ipilimumab at 1 mg/kg IV every 6 weeks.
Of all 56 patients enrolled, 28 (50%) had tumors in the left colon, 3 (5%) had tumors in the right colon, 2 (4%) had tumors in the transverse colon, 16 (29%) had rectal tumors, and 7 (13%) were not specified.
As noted before, 49 patients were evaluable, and the trial met its primary endpoint of responses in at least 17 patients (35%) at 12 weeks. All were partial responses.
Of the remaining patients, 21 (43%) had stable disease, and 11 (22%) had disease progression. Of the latter group, five patients did not have documented radiographic progression at 12 weeks, but they discontinued therapy before restaging because of unequivocal clinical progression.
The best response rate (confirmed and unconfirmed) at any time was 41%.
At a median follow-up of 12.1 months, the median PFS was 5.7 months. The OS data were not mature at the time of data cutoff. However, the median OS was 27 months.
There were two deaths on study, one from myocarditis possibly related to the study treatment, and one from colonic perforation, which was deemed unlikely to be treatment related.
Grade 3 or 4 adverse events included hypomagnesemia (n = 6), acneiform rash (n = 6), increased lipase (n = 5), increased amylase (n = 4), alanine aminotransferase elevation (n = 3), aspartate aminotransferase elevation (n = 3), diarrhea (n = 3), hyophosphatemia (n = 3), and maculopapular rash (n = 3).
‘Disappointing PFS’
In the question and answer session following the presentation, moderator Michael J. Hall, MD, of Fox Chase Cancer Center in Philadelphia, asked whether the response rate seen with the addition of panitumumab was what the investigators expected, independent of the dual–checkpoint inhibitor therapy, and “with the relatively disappointing PFS you saw, what are the plans moving forward with this regimen?”
“These are great questions and thoughts I’ve had as well,” Dr. Lee replied.
He noted that studies of other anti-EGFR and checkpoint inhibitor combinations have had relatively low response rates, and his group’s study was conducted with “an effort to try and get over this immune-cold environment that we know exists in the tumor microenvironment,” he said.
Dr. Lee also acknowledged that the response rate may have been slightly higher than that seen in other studies because of the preponderance of left colon tumors, which are generally more amenable to systemic therapy.
Regarding PFS, Dr. Lee said the analyses of durability of response are still ongoing, and the median PFS was better than that seen in a trial of single-agent panitumumab in a similar population.
The current study was funded by Amgen and Bristol Myers Squibb. Dr. Lee disclosed institutional research funding from the companies, consulting/advising for Pfizer, and travel expenses from Genentech/Roche. Dr. Hall disclosed relationships with Ambry Genetics, AstraZeneca, Caris Life Sciences, Foundation Medicine, InVitae, and Myriad Genetics. He also shares a patent with several Fox Chase investigators for a novel method to investigate hereditary CRC genes.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
The trial was designed to test the combination of panitumumab, ipilimumab, and nivolumab in patients with previously treated, unresectable and/or metastatic, microsatellite stable or mismatch repair–proficient CRC without mutations in KRAS, NRAS, or BRAF.
Among 49 evaluable patients treated with the triplet, 35% had a partial response at 12 weeks of follow-up, which met the trial’s primary response endpoint, according to investigator Michael S. Lee, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Though toxicities were, of course, observed, they were consistent overall with the expected adverse event profiles of anti-EGFR therapy and combination ipilimumab and nivolumab. Correlative studies are ongoing to identify potential biomarkers of response,” Dr. Lee said when presenting the trial results at the 2021 Gastrointestinal Cancers Symposium (Abstract 7).
Immune activation?
The rationale for adding panitumumab to immune checkpoint inhibitors comes, in part, from a trial published in 2014 in The Lancet Oncology. The trial showed that panitumumab was noninferior to cetuximab. Panitumumab was associated with a 22% response rate in patients with KRAS wild-type, metastatic CRC that was refractory to chemotherapy. Progression-free survival (PFS) and overall survival (OS) were similar between the treatment arms.
In addition, in mouse models of RAS wild-type CRC, treatment with an anti-EGFR antibody induced immunogenic cell death.
“Moreover, translational studies of tumor biopsies from patients who were treated with the anti-EGFR antibody cetuximab showed that responders had significant increases in T-cell infiltration and cytolytic activity within tumors after starting treatment,” Dr. Lee said.
In the latter studies, tumor samples taken at the time of disease progression also showed increased expression of immune checkpoint inhibitor pathways, including PD-L1, the primary target of nivolumab, and CTLA-4, the primary target of ipilimumab.
“Given this, we hypothesized that combining anti–PD-1 and anti–CTLA-4 antibodies with anti-EGFR therapy would be synergistic,” Dr. Lee said.
Single-arm study
Investigators enrolled patients with unresectable and/or metastatic CRC in the trial. All patients had disease that was KRAS, NRAS, and BRAF wild-type, and they had either microsatellite stability or proficient mismatch repair. Patients also had to have received one or two prior lines of therapy, not including an anti-EGFR agent.
The patients received panitumumab at 6 mg/kg IV every 2 weeks, nivolumab at 240 mg IV every 2 weeks, and ipilimumab at 1 mg/kg IV every 6 weeks.
Of all 56 patients enrolled, 28 (50%) had tumors in the left colon, 3 (5%) had tumors in the right colon, 2 (4%) had tumors in the transverse colon, 16 (29%) had rectal tumors, and 7 (13%) were not specified.
As noted before, 49 patients were evaluable, and the trial met its primary endpoint of responses in at least 17 patients (35%) at 12 weeks. All were partial responses.
Of the remaining patients, 21 (43%) had stable disease, and 11 (22%) had disease progression. Of the latter group, five patients did not have documented radiographic progression at 12 weeks, but they discontinued therapy before restaging because of unequivocal clinical progression.
The best response rate (confirmed and unconfirmed) at any time was 41%.
At a median follow-up of 12.1 months, the median PFS was 5.7 months. The OS data were not mature at the time of data cutoff. However, the median OS was 27 months.
There were two deaths on study, one from myocarditis possibly related to the study treatment, and one from colonic perforation, which was deemed unlikely to be treatment related.
Grade 3 or 4 adverse events included hypomagnesemia (n = 6), acneiform rash (n = 6), increased lipase (n = 5), increased amylase (n = 4), alanine aminotransferase elevation (n = 3), aspartate aminotransferase elevation (n = 3), diarrhea (n = 3), hyophosphatemia (n = 3), and maculopapular rash (n = 3).
‘Disappointing PFS’
In the question and answer session following the presentation, moderator Michael J. Hall, MD, of Fox Chase Cancer Center in Philadelphia, asked whether the response rate seen with the addition of panitumumab was what the investigators expected, independent of the dual–checkpoint inhibitor therapy, and “with the relatively disappointing PFS you saw, what are the plans moving forward with this regimen?”
“These are great questions and thoughts I’ve had as well,” Dr. Lee replied.
He noted that studies of other anti-EGFR and checkpoint inhibitor combinations have had relatively low response rates, and his group’s study was conducted with “an effort to try and get over this immune-cold environment that we know exists in the tumor microenvironment,” he said.
Dr. Lee also acknowledged that the response rate may have been slightly higher than that seen in other studies because of the preponderance of left colon tumors, which are generally more amenable to systemic therapy.
Regarding PFS, Dr. Lee said the analyses of durability of response are still ongoing, and the median PFS was better than that seen in a trial of single-agent panitumumab in a similar population.
The current study was funded by Amgen and Bristol Myers Squibb. Dr. Lee disclosed institutional research funding from the companies, consulting/advising for Pfizer, and travel expenses from Genentech/Roche. Dr. Hall disclosed relationships with Ambry Genetics, AstraZeneca, Caris Life Sciences, Foundation Medicine, InVitae, and Myriad Genetics. He also shares a patent with several Fox Chase investigators for a novel method to investigate hereditary CRC genes.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
The trial was designed to test the combination of panitumumab, ipilimumab, and nivolumab in patients with previously treated, unresectable and/or metastatic, microsatellite stable or mismatch repair–proficient CRC without mutations in KRAS, NRAS, or BRAF.
Among 49 evaluable patients treated with the triplet, 35% had a partial response at 12 weeks of follow-up, which met the trial’s primary response endpoint, according to investigator Michael S. Lee, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Though toxicities were, of course, observed, they were consistent overall with the expected adverse event profiles of anti-EGFR therapy and combination ipilimumab and nivolumab. Correlative studies are ongoing to identify potential biomarkers of response,” Dr. Lee said when presenting the trial results at the 2021 Gastrointestinal Cancers Symposium (Abstract 7).
Immune activation?
The rationale for adding panitumumab to immune checkpoint inhibitors comes, in part, from a trial published in 2014 in The Lancet Oncology. The trial showed that panitumumab was noninferior to cetuximab. Panitumumab was associated with a 22% response rate in patients with KRAS wild-type, metastatic CRC that was refractory to chemotherapy. Progression-free survival (PFS) and overall survival (OS) were similar between the treatment arms.
In addition, in mouse models of RAS wild-type CRC, treatment with an anti-EGFR antibody induced immunogenic cell death.
“Moreover, translational studies of tumor biopsies from patients who were treated with the anti-EGFR antibody cetuximab showed that responders had significant increases in T-cell infiltration and cytolytic activity within tumors after starting treatment,” Dr. Lee said.
In the latter studies, tumor samples taken at the time of disease progression also showed increased expression of immune checkpoint inhibitor pathways, including PD-L1, the primary target of nivolumab, and CTLA-4, the primary target of ipilimumab.
“Given this, we hypothesized that combining anti–PD-1 and anti–CTLA-4 antibodies with anti-EGFR therapy would be synergistic,” Dr. Lee said.
Single-arm study
Investigators enrolled patients with unresectable and/or metastatic CRC in the trial. All patients had disease that was KRAS, NRAS, and BRAF wild-type, and they had either microsatellite stability or proficient mismatch repair. Patients also had to have received one or two prior lines of therapy, not including an anti-EGFR agent.
The patients received panitumumab at 6 mg/kg IV every 2 weeks, nivolumab at 240 mg IV every 2 weeks, and ipilimumab at 1 mg/kg IV every 6 weeks.
Of all 56 patients enrolled, 28 (50%) had tumors in the left colon, 3 (5%) had tumors in the right colon, 2 (4%) had tumors in the transverse colon, 16 (29%) had rectal tumors, and 7 (13%) were not specified.
As noted before, 49 patients were evaluable, and the trial met its primary endpoint of responses in at least 17 patients (35%) at 12 weeks. All were partial responses.
Of the remaining patients, 21 (43%) had stable disease, and 11 (22%) had disease progression. Of the latter group, five patients did not have documented radiographic progression at 12 weeks, but they discontinued therapy before restaging because of unequivocal clinical progression.
The best response rate (confirmed and unconfirmed) at any time was 41%.
At a median follow-up of 12.1 months, the median PFS was 5.7 months. The OS data were not mature at the time of data cutoff. However, the median OS was 27 months.
There were two deaths on study, one from myocarditis possibly related to the study treatment, and one from colonic perforation, which was deemed unlikely to be treatment related.
Grade 3 or 4 adverse events included hypomagnesemia (n = 6), acneiform rash (n = 6), increased lipase (n = 5), increased amylase (n = 4), alanine aminotransferase elevation (n = 3), aspartate aminotransferase elevation (n = 3), diarrhea (n = 3), hyophosphatemia (n = 3), and maculopapular rash (n = 3).
‘Disappointing PFS’
In the question and answer session following the presentation, moderator Michael J. Hall, MD, of Fox Chase Cancer Center in Philadelphia, asked whether the response rate seen with the addition of panitumumab was what the investigators expected, independent of the dual–checkpoint inhibitor therapy, and “with the relatively disappointing PFS you saw, what are the plans moving forward with this regimen?”
“These are great questions and thoughts I’ve had as well,” Dr. Lee replied.
He noted that studies of other anti-EGFR and checkpoint inhibitor combinations have had relatively low response rates, and his group’s study was conducted with “an effort to try and get over this immune-cold environment that we know exists in the tumor microenvironment,” he said.
Dr. Lee also acknowledged that the response rate may have been slightly higher than that seen in other studies because of the preponderance of left colon tumors, which are generally more amenable to systemic therapy.
Regarding PFS, Dr. Lee said the analyses of durability of response are still ongoing, and the median PFS was better than that seen in a trial of single-agent panitumumab in a similar population.
The current study was funded by Amgen and Bristol Myers Squibb. Dr. Lee disclosed institutional research funding from the companies, consulting/advising for Pfizer, and travel expenses from Genentech/Roche. Dr. Hall disclosed relationships with Ambry Genetics, AstraZeneca, Caris Life Sciences, Foundation Medicine, InVitae, and Myriad Genetics. He also shares a patent with several Fox Chase investigators for a novel method to investigate hereditary CRC genes.
The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
FROM GI CANCERS SYMPOSIUM 2021
Adding liothyronine for hypothyroidism doesn’t up breast cancer risk
“An increasing number of patients ask their physicians for a prescription of combination therapy, often causing tensions. Thus, the question of whether combination therapy does any harm to patients is crucial,” say Tereza Planck, MD, PhD, of Skane University Hospital, Malmo, Sweden, and colleagues, in their article published online Jan. 5 in Thyroid.
“Our data provide reassuring evidence regarding the risk of cancer and mortality,” they stress.
Asked to comment, Caroline T. Nguyen, MD, agrees that the study results are welcome in light of some previous evidence.
“The findings of these [prior] studies were concerning as they suggested an association between T3 and breast cancer, breast cancer-specific mortality, and poorer prognosis with potential estrogen-like activity of T3 on the estrogen receptor,” Dr. Nguyen of the division of endocrinology, diabetes & metabolism at Keck Medical Center of University of Southern California, Los Angeles, told this news organization.
“Therefore, the findings of this paper provide some reassurance, which is important because, as the paper states, the use of T3 is becoming increasingly common.”
Many patients with hypothyroidism opt to add liothyronine
Although the standard treatment for hypothyroidism, levothyroxine, increases free thyroxine (T4) to high-normal levels, it may potentially lower triiodothyronine (T3) to relatively low levels. There is speculation that the imbalance in a subset of patients could explain why some fail to have an adequate reduction of symptoms with levothyroxine alone.
To offset the effect, some add liothyronine (a synthetic version of T3) to levothyroxine treatment as so-called “combination therapy.” However, a long-term study conducted in Scotland showed a borderline significant increase in breast cancer risk with the combination, raising concern.
To further investigate, Dr. Planck and coauthors used Swedish adult population data, identifying 575,461 individuals who had made at least three purchases of thyroid hormone therapy between July 2005 and December 2017, and had no history of breast cancer at the time of their first prescription.
Among the individuals, 11,147 had made at least three purchases of LT3, including combinations with LT4. LT4-only users were an average age of 54.4 years, and the average age of those who also took LT3 was 44.7 years.
Over a median follow-up of 8.1 years, there was no significantly increased risk of breast cancer among women treated with LT3 plus LT4 versus LT4 alone (hazard ratio, 0.93), after adjusting for differences in age, sex, previous thyroid cancer, previous other cancer, use of antithyroid preparations, use of sex hormones, and dose.
Further evaluation of women as well as men showed those treated with LT3 also had no increased incidence of any cancer (HR, 0.97).
In dose-adjusted models, LT3 treatment did, surprisingly, appear to have a protective effect in terms of all-cause mortality (HR, 0.69) and any cancer mortality (HR, 0.78) for men and women.
However, the implications of these latter results remain uncertain, first author Dr. Planck said in an interview.
“We think the data on reduced mortality should be interpreted with caution, as we only observe the differences in the models adjusting for dose,” she noted.
LT3 treatment still considered ‘experimental’
Despite the dramatic increase in LT3 prescribing in recent years noted by the authors, as many as five systematic reviews/meta-analyses have shown no superiority of combination therapy over LT4 alone in terms of hypothyroid symptoms, quality of life, or patient preference.
As a result, many international guidelines still consider the combination-treatment approach to be experimental.
Other trials that have raised concerns about the combination include previous large, prospective Swedish studies that have linked higher endogenous T3 levels to breast cancer in postmenopausal women.
As for the mechanism, some small experimental studies have suggested an estrogenlike effect whereby T3 could enhance the proliferation of breast cancer cells.
On a broader level, thyroid hormones, in general, have been extensively studied in cancer research as possibly promoting cancer cell proliferation in a variety of cancer types.
However, the current findings should lay some of those concerns to rest, Dr. Planck reiterated: “Our data provide reassuring evidence regarding the risk of cancer and mortality.”
“We did not identify any increase in breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, or breast cancer mortality between individuals using LT3 and LT4 treatment.”
The authors and Nguyen have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“An increasing number of patients ask their physicians for a prescription of combination therapy, often causing tensions. Thus, the question of whether combination therapy does any harm to patients is crucial,” say Tereza Planck, MD, PhD, of Skane University Hospital, Malmo, Sweden, and colleagues, in their article published online Jan. 5 in Thyroid.
“Our data provide reassuring evidence regarding the risk of cancer and mortality,” they stress.
Asked to comment, Caroline T. Nguyen, MD, agrees that the study results are welcome in light of some previous evidence.
“The findings of these [prior] studies were concerning as they suggested an association between T3 and breast cancer, breast cancer-specific mortality, and poorer prognosis with potential estrogen-like activity of T3 on the estrogen receptor,” Dr. Nguyen of the division of endocrinology, diabetes & metabolism at Keck Medical Center of University of Southern California, Los Angeles, told this news organization.
“Therefore, the findings of this paper provide some reassurance, which is important because, as the paper states, the use of T3 is becoming increasingly common.”
Many patients with hypothyroidism opt to add liothyronine
Although the standard treatment for hypothyroidism, levothyroxine, increases free thyroxine (T4) to high-normal levels, it may potentially lower triiodothyronine (T3) to relatively low levels. There is speculation that the imbalance in a subset of patients could explain why some fail to have an adequate reduction of symptoms with levothyroxine alone.
To offset the effect, some add liothyronine (a synthetic version of T3) to levothyroxine treatment as so-called “combination therapy.” However, a long-term study conducted in Scotland showed a borderline significant increase in breast cancer risk with the combination, raising concern.
To further investigate, Dr. Planck and coauthors used Swedish adult population data, identifying 575,461 individuals who had made at least three purchases of thyroid hormone therapy between July 2005 and December 2017, and had no history of breast cancer at the time of their first prescription.
Among the individuals, 11,147 had made at least three purchases of LT3, including combinations with LT4. LT4-only users were an average age of 54.4 years, and the average age of those who also took LT3 was 44.7 years.
Over a median follow-up of 8.1 years, there was no significantly increased risk of breast cancer among women treated with LT3 plus LT4 versus LT4 alone (hazard ratio, 0.93), after adjusting for differences in age, sex, previous thyroid cancer, previous other cancer, use of antithyroid preparations, use of sex hormones, and dose.
Further evaluation of women as well as men showed those treated with LT3 also had no increased incidence of any cancer (HR, 0.97).
In dose-adjusted models, LT3 treatment did, surprisingly, appear to have a protective effect in terms of all-cause mortality (HR, 0.69) and any cancer mortality (HR, 0.78) for men and women.
However, the implications of these latter results remain uncertain, first author Dr. Planck said in an interview.
“We think the data on reduced mortality should be interpreted with caution, as we only observe the differences in the models adjusting for dose,” she noted.
LT3 treatment still considered ‘experimental’
Despite the dramatic increase in LT3 prescribing in recent years noted by the authors, as many as five systematic reviews/meta-analyses have shown no superiority of combination therapy over LT4 alone in terms of hypothyroid symptoms, quality of life, or patient preference.
As a result, many international guidelines still consider the combination-treatment approach to be experimental.
Other trials that have raised concerns about the combination include previous large, prospective Swedish studies that have linked higher endogenous T3 levels to breast cancer in postmenopausal women.
As for the mechanism, some small experimental studies have suggested an estrogenlike effect whereby T3 could enhance the proliferation of breast cancer cells.
On a broader level, thyroid hormones, in general, have been extensively studied in cancer research as possibly promoting cancer cell proliferation in a variety of cancer types.
However, the current findings should lay some of those concerns to rest, Dr. Planck reiterated: “Our data provide reassuring evidence regarding the risk of cancer and mortality.”
“We did not identify any increase in breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, or breast cancer mortality between individuals using LT3 and LT4 treatment.”
The authors and Nguyen have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“An increasing number of patients ask their physicians for a prescription of combination therapy, often causing tensions. Thus, the question of whether combination therapy does any harm to patients is crucial,” say Tereza Planck, MD, PhD, of Skane University Hospital, Malmo, Sweden, and colleagues, in their article published online Jan. 5 in Thyroid.
“Our data provide reassuring evidence regarding the risk of cancer and mortality,” they stress.
Asked to comment, Caroline T. Nguyen, MD, agrees that the study results are welcome in light of some previous evidence.
“The findings of these [prior] studies were concerning as they suggested an association between T3 and breast cancer, breast cancer-specific mortality, and poorer prognosis with potential estrogen-like activity of T3 on the estrogen receptor,” Dr. Nguyen of the division of endocrinology, diabetes & metabolism at Keck Medical Center of University of Southern California, Los Angeles, told this news organization.
“Therefore, the findings of this paper provide some reassurance, which is important because, as the paper states, the use of T3 is becoming increasingly common.”
Many patients with hypothyroidism opt to add liothyronine
Although the standard treatment for hypothyroidism, levothyroxine, increases free thyroxine (T4) to high-normal levels, it may potentially lower triiodothyronine (T3) to relatively low levels. There is speculation that the imbalance in a subset of patients could explain why some fail to have an adequate reduction of symptoms with levothyroxine alone.
To offset the effect, some add liothyronine (a synthetic version of T3) to levothyroxine treatment as so-called “combination therapy.” However, a long-term study conducted in Scotland showed a borderline significant increase in breast cancer risk with the combination, raising concern.
To further investigate, Dr. Planck and coauthors used Swedish adult population data, identifying 575,461 individuals who had made at least three purchases of thyroid hormone therapy between July 2005 and December 2017, and had no history of breast cancer at the time of their first prescription.
Among the individuals, 11,147 had made at least three purchases of LT3, including combinations with LT4. LT4-only users were an average age of 54.4 years, and the average age of those who also took LT3 was 44.7 years.
Over a median follow-up of 8.1 years, there was no significantly increased risk of breast cancer among women treated with LT3 plus LT4 versus LT4 alone (hazard ratio, 0.93), after adjusting for differences in age, sex, previous thyroid cancer, previous other cancer, use of antithyroid preparations, use of sex hormones, and dose.
Further evaluation of women as well as men showed those treated with LT3 also had no increased incidence of any cancer (HR, 0.97).
In dose-adjusted models, LT3 treatment did, surprisingly, appear to have a protective effect in terms of all-cause mortality (HR, 0.69) and any cancer mortality (HR, 0.78) for men and women.
However, the implications of these latter results remain uncertain, first author Dr. Planck said in an interview.
“We think the data on reduced mortality should be interpreted with caution, as we only observe the differences in the models adjusting for dose,” she noted.
LT3 treatment still considered ‘experimental’
Despite the dramatic increase in LT3 prescribing in recent years noted by the authors, as many as five systematic reviews/meta-analyses have shown no superiority of combination therapy over LT4 alone in terms of hypothyroid symptoms, quality of life, or patient preference.
As a result, many international guidelines still consider the combination-treatment approach to be experimental.
Other trials that have raised concerns about the combination include previous large, prospective Swedish studies that have linked higher endogenous T3 levels to breast cancer in postmenopausal women.
As for the mechanism, some small experimental studies have suggested an estrogenlike effect whereby T3 could enhance the proliferation of breast cancer cells.
On a broader level, thyroid hormones, in general, have been extensively studied in cancer research as possibly promoting cancer cell proliferation in a variety of cancer types.
However, the current findings should lay some of those concerns to rest, Dr. Planck reiterated: “Our data provide reassuring evidence regarding the risk of cancer and mortality.”
“We did not identify any increase in breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, or breast cancer mortality between individuals using LT3 and LT4 treatment.”
The authors and Nguyen have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.