AVAHO

It’s now confirmed: What you eat does affect your risk of developing colorectal cancer (CRC).

An umbrella review of studies and meta-analyses found “convincing evidence of an association between a lower CRC risk and higher intakes of dietary fiber, dietary calcium, and yogurt and lower intakes of alcohol and red meat.”

However, more research is needed to address the link between CRC and other foods, including dairy products, whole grains, processed meat, and specific dietary patterns, the authors conclude.

“We can say that the existing recommendations for diet in the primary prevention of colorectal cancer is confirmed,” said lead author Nathorn Chaiyakunapruk, PharmD, PhD, professor of pharmacology at the University of Utah, Salt Lake City.

“It makes sense to encourage healthy diet, including those rich in fruits, vegetables, grains, and low-fat dairy, and reducing red meat and alcohol intake,” he said in an interview. “However, some of them may not yet have convincing evidence to fully support the claim.”

Other lifestyle factors, including excess weight and physical inactivity, also play a role in cancer risk. Dr. Chaiyakunapruk pointed out that their review was focused only on diet and that they had set out to confirm factors for which there was strong and convincing evidence.

The review was published online in JAMA Network Open.

The umbrella review of 45 meta-analyses found 109 associations. Overall, 35 of these 109 associations (32.1%) were nominally statistically significant, as determined on the basis of random-effects meta-analysis models, the researchers explained.

Convincing evidence was found for an increase in the risk for CRC with higher versus lower red meat consumption and with heavy alcohol intake (defined as more than four drinks per day, compared with no drinks per day or occasional drinks).

In addition, convincing evidence was found for three inverse associations: a decrease in the risk for CRC was associated with higher versus lower intake of total dietary fiber, calcium, and yogurt.

The researchers noted that, although not completely convincing, there was highly suggestive evidence for another association: a link between diet and CRC incidence. A higher intake of total dairy products (e.g., milk, cheese, and yogurt) was associated with significant risk reduction, in comparison with lower intake. A moderate intake of alcohol (from one to three drinks but not more than four per day) was associated with an increase in incidence in comparison with no drinks or an occasional drink.

Evidence suggested a reduced risk in association with several lifestyle behaviors, including adherence to a Mediterranean diet, a healthy diet, a pesco-vegetarian or semivegetarian diet, and the intake of whole grains, nonfermented milk, and supplemental calcium.

The evidence suggested that adherence to a Western diet and intake of processed meat were associated with an increased risk for CRC.

There was weak or no evidence for the remaining associations.
 

Existing cancer prevention guidelines

The findings support the existing cancer prevention dietary guidance and recommendations from the American Institute for Cancer Research, commented the institute’s director of nutrition programs, Sheena Swanner Patel, MS, RDN. The study confirms that dietary factors play a strong role in lowering CRC risk.

“AICR’s report found strong evidence for whole grains, foods containing dietary fiber, dairy products, and calcium supplements decreasing risk for colorectal cancer,” she said. “Specifically, eating 90 g or three servings of whole grains per day is associated with a 17% decrease in colorectal cancer risk.”

Ms. Patel added that the AICR’s report also suggested there was strong evidence that eating large amounts of red and processed meat, drinking alcohol excessively, and carrying extra body weight increased the risk for CRC.

Many previous studies have suggested a link between diet and CRC risk. One recent study suggested that, among all cancers, CRC has the highest proportion of diet-related cases (38.3%). The next highest were cancers of the mouth, pharynx, and larynx, for which almost 26% of cases were linked to diet, followed by endometrial cancer, postmenopausal breast cancer, and cancers of the kidney, stomach, liver, pancreas, and esophagus.

Neither Dr. Chaiyakunapruk and coauthors nor Ms. Patel disclosed any relevant financial relationships.

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

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.

It’s now confirmed: What you eat does affect your risk of developing colorectal cancer (CRC).

An umbrella review of studies and meta-analyses found “convincing evidence of an association between a lower CRC risk and higher intakes of dietary fiber, dietary calcium, and yogurt and lower intakes of alcohol and red meat.”

However, more research is needed to address the link between CRC and other foods, including dairy products, whole grains, processed meat, and specific dietary patterns, the authors conclude.

“We can say that the existing recommendations for diet in the primary prevention of colorectal cancer is confirmed,” said lead author Nathorn Chaiyakunapruk, PharmD, PhD, professor of pharmacology at the University of Utah, Salt Lake City.

“It makes sense to encourage healthy diet, including those rich in fruits, vegetables, grains, and low-fat dairy, and reducing red meat and alcohol intake,” he said in an interview. “However, some of them may not yet have convincing evidence to fully support the claim.”

Other lifestyle factors, including excess weight and physical inactivity, also play a role in cancer risk. Dr. Chaiyakunapruk pointed out that their review was focused only on diet and that they had set out to confirm factors for which there was strong and convincing evidence.

The review was published online in JAMA Network Open.

The umbrella review of 45 meta-analyses found 109 associations. Overall, 35 of these 109 associations (32.1%) were nominally statistically significant, as determined on the basis of random-effects meta-analysis models, the researchers explained.

Convincing evidence was found for an increase in the risk for CRC with higher versus lower red meat consumption and with heavy alcohol intake (defined as more than four drinks per day, compared with no drinks per day or occasional drinks).

In addition, convincing evidence was found for three inverse associations: a decrease in the risk for CRC was associated with higher versus lower intake of total dietary fiber, calcium, and yogurt.

The researchers noted that, although not completely convincing, there was highly suggestive evidence for another association: a link between diet and CRC incidence. A higher intake of total dairy products (e.g., milk, cheese, and yogurt) was associated with significant risk reduction, in comparison with lower intake. A moderate intake of alcohol (from one to three drinks but not more than four per day) was associated with an increase in incidence in comparison with no drinks or an occasional drink.

Evidence suggested a reduced risk in association with several lifestyle behaviors, including adherence to a Mediterranean diet, a healthy diet, a pesco-vegetarian or semivegetarian diet, and the intake of whole grains, nonfermented milk, and supplemental calcium.

The evidence suggested that adherence to a Western diet and intake of processed meat were associated with an increased risk for CRC.

There was weak or no evidence for the remaining associations.
 

Existing cancer prevention guidelines

The findings support the existing cancer prevention dietary guidance and recommendations from the American Institute for Cancer Research, commented the institute’s director of nutrition programs, Sheena Swanner Patel, MS, RDN. The study confirms that dietary factors play a strong role in lowering CRC risk.

“AICR’s report found strong evidence for whole grains, foods containing dietary fiber, dairy products, and calcium supplements decreasing risk for colorectal cancer,” she said. “Specifically, eating 90 g or three servings of whole grains per day is associated with a 17% decrease in colorectal cancer risk.”

Ms. Patel added that the AICR’s report also suggested there was strong evidence that eating large amounts of red and processed meat, drinking alcohol excessively, and carrying extra body weight increased the risk for CRC.

Many previous studies have suggested a link between diet and CRC risk. One recent study suggested that, among all cancers, CRC has the highest proportion of diet-related cases (38.3%). The next highest were cancers of the mouth, pharynx, and larynx, for which almost 26% of cases were linked to diet, followed by endometrial cancer, postmenopausal breast cancer, and cancers of the kidney, stomach, liver, pancreas, and esophagus.

Neither Dr. Chaiyakunapruk and coauthors nor Ms. Patel disclosed any relevant financial relationships.

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

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.

It’s now confirmed: What you eat does affect your risk of developing colorectal cancer (CRC).

An umbrella review of studies and meta-analyses found “convincing evidence of an association between a lower CRC risk and higher intakes of dietary fiber, dietary calcium, and yogurt and lower intakes of alcohol and red meat.”

However, more research is needed to address the link between CRC and other foods, including dairy products, whole grains, processed meat, and specific dietary patterns, the authors conclude.

“We can say that the existing recommendations for diet in the primary prevention of colorectal cancer is confirmed,” said lead author Nathorn Chaiyakunapruk, PharmD, PhD, professor of pharmacology at the University of Utah, Salt Lake City.

“It makes sense to encourage healthy diet, including those rich in fruits, vegetables, grains, and low-fat dairy, and reducing red meat and alcohol intake,” he said in an interview. “However, some of them may not yet have convincing evidence to fully support the claim.”

Other lifestyle factors, including excess weight and physical inactivity, also play a role in cancer risk. Dr. Chaiyakunapruk pointed out that their review was focused only on diet and that they had set out to confirm factors for which there was strong and convincing evidence.

The review was published online in JAMA Network Open.

The umbrella review of 45 meta-analyses found 109 associations. Overall, 35 of these 109 associations (32.1%) were nominally statistically significant, as determined on the basis of random-effects meta-analysis models, the researchers explained.

Convincing evidence was found for an increase in the risk for CRC with higher versus lower red meat consumption and with heavy alcohol intake (defined as more than four drinks per day, compared with no drinks per day or occasional drinks).

In addition, convincing evidence was found for three inverse associations: a decrease in the risk for CRC was associated with higher versus lower intake of total dietary fiber, calcium, and yogurt.

The researchers noted that, although not completely convincing, there was highly suggestive evidence for another association: a link between diet and CRC incidence. A higher intake of total dairy products (e.g., milk, cheese, and yogurt) was associated with significant risk reduction, in comparison with lower intake. A moderate intake of alcohol (from one to three drinks but not more than four per day) was associated with an increase in incidence in comparison with no drinks or an occasional drink.

Evidence suggested a reduced risk in association with several lifestyle behaviors, including adherence to a Mediterranean diet, a healthy diet, a pesco-vegetarian or semivegetarian diet, and the intake of whole grains, nonfermented milk, and supplemental calcium.

The evidence suggested that adherence to a Western diet and intake of processed meat were associated with an increased risk for CRC.

There was weak or no evidence for the remaining associations.
 

Existing cancer prevention guidelines

The findings support the existing cancer prevention dietary guidance and recommendations from the American Institute for Cancer Research, commented the institute’s director of nutrition programs, Sheena Swanner Patel, MS, RDN. The study confirms that dietary factors play a strong role in lowering CRC risk.

“AICR’s report found strong evidence for whole grains, foods containing dietary fiber, dairy products, and calcium supplements decreasing risk for colorectal cancer,” she said. “Specifically, eating 90 g or three servings of whole grains per day is associated with a 17% decrease in colorectal cancer risk.”

Ms. Patel added that the AICR’s report also suggested there was strong evidence that eating large amounts of red and processed meat, drinking alcohol excessively, and carrying extra body weight increased the risk for CRC.

Many previous studies have suggested a link between diet and CRC risk. One recent study suggested that, among all cancers, CRC has the highest proportion of diet-related cases (38.3%). The next highest were cancers of the mouth, pharynx, and larynx, for which almost 26% of cases were linked to diet, followed by endometrial cancer, postmenopausal breast cancer, and cancers of the kidney, stomach, liver, pancreas, and esophagus.

Neither Dr. Chaiyakunapruk and coauthors nor Ms. Patel disclosed any relevant financial relationships.

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

Help your patients understand colorectal cancer prevention and screening options by sharing AGA’s patient education from the GI Patient Center: www.gastro.org/CRC.

Patients with multiple myeloma that has continued to progress despite many lines of therapy have shown deep and durable responses to a new chimeric antigen receptor (CAR) T-cell therapy, idecabtagene vicleucel (ide-cel, under development by Bristol-Myers Squibb and Bluebird Bio).

An expert not involved in the trial described the results as “phenomenal.”

Krina Patel, MD, an associate professor in the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center, Houston, said that “the response rate of 73% in a patient population with a median of six lines of therapy, and with one-third of those patients achieving a deep response of complete response or better, is phenomenal.”

“We are very excited as a myeloma community for this study of idecabtagene vicleucel for relapsed/refractory patients,” Dr. Patel said.

The new data on ide-cell, from a trial in 128 patients, were published Feb. 25 in the New England Journal of Medicine.

Lead investigator of the study Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, said: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

Both experts highlighted the poor prognosis for this population of relapsed/refractory patients. Recent decades have seen a flurry of new agents for myeloma, and there are now three main classes of agents: immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies. Nevertheless, in some patients, the disease continues to progress. For patients who have failed all three classes of drugs, the median progression-free survival is about 3-4 months, with a median overall survival of 8-9 months.
 

Product is awaiting approval

Ide-cel is currently awaiting FDA approval, with a decision date slated for March 27.

Several CAR T-cell products are already marketed for use in certain leukemias and lymphomas, and there is another for use in multiple myeloma, ciltacabtagene autoleucel (cilta-cel, under development by Janssen), that is awaiting approval in Europe.
 

Strong and sustained responses

The trial involved 128 patients treated with ide-cel infusions. At the time of data cutoff for this report (Jan. 14, 2020), 62 patients remained in the primary study. Of the 128 treated patients, the median age was 61 years and the median time since diagnosis was 6 years. About half (51%) had a high tumor burden (≥50% bone marrow plasma cells), 39% had extramedullary disease, 16% had stage III disease, and 35% had a high-risk cytogenetic abnormality, defined as del(17p), t(4;14), or t(14;16).

Patients in the cohort had received a median of six previous antimyeloma regimens (range, 3-16), and most of the patients (120, 94%) had undergone autologous hematopoietic stem cell transplants. In addition, the majority of patients (84%) had disease that was triple refractory (to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody), 60% had disease that was penta exposed (to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab), and 26% had disease that was penta refractory.

At a median follow-up of 13.3 months, 94 of 128 patients (73%) showed a response to therapy (P < .001), with 42 (33%) showing a complete or stringent complete response, and 67 patients (52%) showing a “very good partial response or better.”

Overall median progression-free survival was 8.8 months at the 450×106 dose but more than double that (20.2 months) for patients who achieved a complete or stringent complete response. Estimated median overall survival was 19.4 months, with an overall survival of 78% at 12 months. The authors noted that overall survival data are not yet mature.

After experiencing disease progression, 28 patients were retreated with ide-cel, with 6 patients showing a second response. The durations of response ranged from 1.9 to 6.8 months.

All patients in the cohort experienced adverse events, primarily grade 3 or 4 events that occurred in 127 patients (99%). The most common events reported were hematologic toxicities, including neutropenia in 114 patients (89%), anemia in 77 (60%), and thrombocytopenia in 67 (52%), and were at least partially related to the lymphodepleting chemotherapy administered before ide-cel infusion, the authors note. Cytokine-release syndrome occurred in 107 patients (84%), primarily grade 1 or 2.

“Results of the KarMMa study support substantial antitumor activity for ide-cel across a target dose range of 150×106 to 450×106 CAR+ T cells,” the authors conclude. “The 450×106 dose appeared to be somewhat more effective than the other doses.”
 

New option?

“What this study further highlights is that higher cell dose tends to increase cell expansion, which correlates to improved response and duration of response,” said Dr. Patel.

Importantly, multiple vulnerable subgroups experienced impressive outcomes, such as those who are older or with high risk or extramedullary disease, she noted.

“My patients who have undergone this therapy, albeit on other clinical trials, all say that their quality of life during this time of remission is priceless,” Dr. Patel added. “The is the first therapy in the relapsed/refractory setting that allows patients to have a significant chemo-free period. We need to find more ways to do this for our patients.”

The study was supported by Bluebird Bio and Bristol-Myers Squibb. Dr. Patel has served on the advisory board for Janssen and Bristol-Myers Squibb. She also reports a speaking engagement with Oncopeptides. Dr. Munshi acts as a consultant for several pharmaceutical companies, and many coauthors also have relationships with industry, as listed in the original article.

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

Patients with multiple myeloma that has continued to progress despite many lines of therapy have shown deep and durable responses to a new chimeric antigen receptor (CAR) T-cell therapy, idecabtagene vicleucel (ide-cel, under development by Bristol-Myers Squibb and Bluebird Bio).

An expert not involved in the trial described the results as “phenomenal.”

Krina Patel, MD, an associate professor in the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center, Houston, said that “the response rate of 73% in a patient population with a median of six lines of therapy, and with one-third of those patients achieving a deep response of complete response or better, is phenomenal.”

“We are very excited as a myeloma community for this study of idecabtagene vicleucel for relapsed/refractory patients,” Dr. Patel said.

The new data on ide-cell, from a trial in 128 patients, were published Feb. 25 in the New England Journal of Medicine.

Lead investigator of the study Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, said: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

Both experts highlighted the poor prognosis for this population of relapsed/refractory patients. Recent decades have seen a flurry of new agents for myeloma, and there are now three main classes of agents: immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies. Nevertheless, in some patients, the disease continues to progress. For patients who have failed all three classes of drugs, the median progression-free survival is about 3-4 months, with a median overall survival of 8-9 months.
 

Product is awaiting approval

Ide-cel is currently awaiting FDA approval, with a decision date slated for March 27.

Several CAR T-cell products are already marketed for use in certain leukemias and lymphomas, and there is another for use in multiple myeloma, ciltacabtagene autoleucel (cilta-cel, under development by Janssen), that is awaiting approval in Europe.
 

Strong and sustained responses

The trial involved 128 patients treated with ide-cel infusions. At the time of data cutoff for this report (Jan. 14, 2020), 62 patients remained in the primary study. Of the 128 treated patients, the median age was 61 years and the median time since diagnosis was 6 years. About half (51%) had a high tumor burden (≥50% bone marrow plasma cells), 39% had extramedullary disease, 16% had stage III disease, and 35% had a high-risk cytogenetic abnormality, defined as del(17p), t(4;14), or t(14;16).

Patients in the cohort had received a median of six previous antimyeloma regimens (range, 3-16), and most of the patients (120, 94%) had undergone autologous hematopoietic stem cell transplants. In addition, the majority of patients (84%) had disease that was triple refractory (to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody), 60% had disease that was penta exposed (to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab), and 26% had disease that was penta refractory.

At a median follow-up of 13.3 months, 94 of 128 patients (73%) showed a response to therapy (P < .001), with 42 (33%) showing a complete or stringent complete response, and 67 patients (52%) showing a “very good partial response or better.”

Overall median progression-free survival was 8.8 months at the 450×106 dose but more than double that (20.2 months) for patients who achieved a complete or stringent complete response. Estimated median overall survival was 19.4 months, with an overall survival of 78% at 12 months. The authors noted that overall survival data are not yet mature.

After experiencing disease progression, 28 patients were retreated with ide-cel, with 6 patients showing a second response. The durations of response ranged from 1.9 to 6.8 months.

All patients in the cohort experienced adverse events, primarily grade 3 or 4 events that occurred in 127 patients (99%). The most common events reported were hematologic toxicities, including neutropenia in 114 patients (89%), anemia in 77 (60%), and thrombocytopenia in 67 (52%), and were at least partially related to the lymphodepleting chemotherapy administered before ide-cel infusion, the authors note. Cytokine-release syndrome occurred in 107 patients (84%), primarily grade 1 or 2.

“Results of the KarMMa study support substantial antitumor activity for ide-cel across a target dose range of 150×106 to 450×106 CAR+ T cells,” the authors conclude. “The 450×106 dose appeared to be somewhat more effective than the other doses.”
 

New option?

“What this study further highlights is that higher cell dose tends to increase cell expansion, which correlates to improved response and duration of response,” said Dr. Patel.

Importantly, multiple vulnerable subgroups experienced impressive outcomes, such as those who are older or with high risk or extramedullary disease, she noted.

“My patients who have undergone this therapy, albeit on other clinical trials, all say that their quality of life during this time of remission is priceless,” Dr. Patel added. “The is the first therapy in the relapsed/refractory setting that allows patients to have a significant chemo-free period. We need to find more ways to do this for our patients.”

The study was supported by Bluebird Bio and Bristol-Myers Squibb. Dr. Patel has served on the advisory board for Janssen and Bristol-Myers Squibb. She also reports a speaking engagement with Oncopeptides. Dr. Munshi acts as a consultant for several pharmaceutical companies, and many coauthors also have relationships with industry, as listed in the original article.

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

Patients with multiple myeloma that has continued to progress despite many lines of therapy have shown deep and durable responses to a new chimeric antigen receptor (CAR) T-cell therapy, idecabtagene vicleucel (ide-cel, under development by Bristol-Myers Squibb and Bluebird Bio).

An expert not involved in the trial described the results as “phenomenal.”

Krina Patel, MD, an associate professor in the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center, Houston, said that “the response rate of 73% in a patient population with a median of six lines of therapy, and with one-third of those patients achieving a deep response of complete response or better, is phenomenal.”

“We are very excited as a myeloma community for this study of idecabtagene vicleucel for relapsed/refractory patients,” Dr. Patel said.

The new data on ide-cell, from a trial in 128 patients, were published Feb. 25 in the New England Journal of Medicine.

Lead investigator of the study Nikhil Munshi, MD, of Dana-Farber Cancer Institute, Boston, said: “The results of this trial represent a true turning point in the treatment of this disease. In my 30 years of treating myeloma, I have not seen any other therapy as effective in this group of patients.”

Both experts highlighted the poor prognosis for this population of relapsed/refractory patients. Recent decades have seen a flurry of new agents for myeloma, and there are now three main classes of agents: immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies. Nevertheless, in some patients, the disease continues to progress. For patients who have failed all three classes of drugs, the median progression-free survival is about 3-4 months, with a median overall survival of 8-9 months.
 

Product is awaiting approval

Ide-cel is currently awaiting FDA approval, with a decision date slated for March 27.

Several CAR T-cell products are already marketed for use in certain leukemias and lymphomas, and there is another for use in multiple myeloma, ciltacabtagene autoleucel (cilta-cel, under development by Janssen), that is awaiting approval in Europe.
 

Strong and sustained responses

The trial involved 128 patients treated with ide-cel infusions. At the time of data cutoff for this report (Jan. 14, 2020), 62 patients remained in the primary study. Of the 128 treated patients, the median age was 61 years and the median time since diagnosis was 6 years. About half (51%) had a high tumor burden (≥50% bone marrow plasma cells), 39% had extramedullary disease, 16% had stage III disease, and 35% had a high-risk cytogenetic abnormality, defined as del(17p), t(4;14), or t(14;16).

Patients in the cohort had received a median of six previous antimyeloma regimens (range, 3-16), and most of the patients (120, 94%) had undergone autologous hematopoietic stem cell transplants. In addition, the majority of patients (84%) had disease that was triple refractory (to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody), 60% had disease that was penta exposed (to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab), and 26% had disease that was penta refractory.

At a median follow-up of 13.3 months, 94 of 128 patients (73%) showed a response to therapy (P < .001), with 42 (33%) showing a complete or stringent complete response, and 67 patients (52%) showing a “very good partial response or better.”

Overall median progression-free survival was 8.8 months at the 450×106 dose but more than double that (20.2 months) for patients who achieved a complete or stringent complete response. Estimated median overall survival was 19.4 months, with an overall survival of 78% at 12 months. The authors noted that overall survival data are not yet mature.

After experiencing disease progression, 28 patients were retreated with ide-cel, with 6 patients showing a second response. The durations of response ranged from 1.9 to 6.8 months.

All patients in the cohort experienced adverse events, primarily grade 3 or 4 events that occurred in 127 patients (99%). The most common events reported were hematologic toxicities, including neutropenia in 114 patients (89%), anemia in 77 (60%), and thrombocytopenia in 67 (52%), and were at least partially related to the lymphodepleting chemotherapy administered before ide-cel infusion, the authors note. Cytokine-release syndrome occurred in 107 patients (84%), primarily grade 1 or 2.

“Results of the KarMMa study support substantial antitumor activity for ide-cel across a target dose range of 150×106 to 450×106 CAR+ T cells,” the authors conclude. “The 450×106 dose appeared to be somewhat more effective than the other doses.”
 

New option?

“What this study further highlights is that higher cell dose tends to increase cell expansion, which correlates to improved response and duration of response,” said Dr. Patel.

Importantly, multiple vulnerable subgroups experienced impressive outcomes, such as those who are older or with high risk or extramedullary disease, she noted.

“My patients who have undergone this therapy, albeit on other clinical trials, all say that their quality of life during this time of remission is priceless,” Dr. Patel added. “The is the first therapy in the relapsed/refractory setting that allows patients to have a significant chemo-free period. We need to find more ways to do this for our patients.”

The study was supported by Bluebird Bio and Bristol-Myers Squibb. Dr. Patel has served on the advisory board for Janssen and Bristol-Myers Squibb. She also reports a speaking engagement with Oncopeptides. Dr. Munshi acts as a consultant for several pharmaceutical companies, and many coauthors also have relationships with industry, as listed in the original article.

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

Axillary adenopathy, or swelling under the armpit, has been reported by women after receiving the Pfizer-BioNTech and Moderna COVID-19 vaccines, but it is also a common symptom of breast cancer.

Clinicians should therefore consider recent COVID-19 vaccination history in the differential diagnosis of patients who present with unilateral axillary adenopathy, according to a new article.

“We noticed an increasing number of patients with swollen lymph nodes on just one side/one underarm who presented for routine screening mammography or ultrasound, and some women who actually felt these swollen nodes,” said author Katerina Dodelzon, MD, assistant professor of clinical radiology at Weill Cornell Medicine, New York.

“Historically, swollen lymph nodes on just one side are relatively rare and are an uncommon occurrence on screening mammography – seen only 0.02%-0.04% of the time – and is a sign that alerts a radiologist to exclude the presence of breast malignancy on that side,” she added.

In an article published in Clinical Imaging, Dr. Dodelzon and colleagues described four cases involving women who received a COVID-19 vaccine and then sought breast screening. In describing these cases, the authors sought “to inform the medical community to consider this benign and self-resolving diagnosis in the setting of what can be alarming presentation of unilateral axillary adenopathy.”

They hope they will decrease unnecessary biopsies and help reassure patients.

Adenopathy has been reported in association with other vaccines, such as the bacille Calmette-Guérin vaccine, influenza vaccines, and the human papillomavirus vaccine, commented Jessica W. T. Leung, MD, president of the Society of Breast Imaging.

“It’s too early to say if there is something different about the COVID-19 vaccines,” said Dr. Leung, who is also professor of diagnostic radiology and deputy chair of breast imaging at the University of Texas MD Anderson Cancer Center, Houston.

“The two vaccines that are currently in use – Pfizer and Moderna – are both mRNA vaccines, and it is unknown if those will give a stronger immune response,” she said. “If the Johnson & Johnson and AstraZeneca vaccines do become available, it will be interesting to see if they elicit as strong a response, since they are not mRNA vaccines. At this time, we have no data to say one way or the other.”

Dr. Leung also noted that these latest vaccine reactions may be getting more attention because “it is COVID-19 related, and everything related to COVID-19 gets more attention.

“It may also be more noticeable because of the large number of people getting vaccinated within a short period of time in an effort to contain the pandemic, and this is not the case with the other vaccines,” she said.
 

New recommendations from SBI

The SBI recently issued recommendations to clinicians that women who experience axillary adenopathy and who have recently been vaccinated on the same side on which the adenopathy occurs be followed for a few weeks to see whether the lymph nodes return to normal, rather than undergo biopsy.

“Many practices are now routinely inquiring about history of recent vaccination and on which side it was given,” Dr. Dodelzon said. She emphasized that women should feel empowered to share that history if they are not asked.

“Letting your mammography technologist or breast imager know that you have recently been vaccinated, and on which side, will provide the breast imager more accurate context within which to interpret the results,” she said.

In addition, the SBI recommends that, if feasible, women schedule routine screening mammography either before the first dose of the COVID-19 vaccine or 4-6 weeks after the second dose to avoid a false-positive finding.

“We want to emphasize that screening mammography is very important, and if possible, to schedule it around the vaccine,” commented Dr. Leung. “But that may not be possible, as most of us don’t have a choice when to get the vaccine.”

If it is not possible to reschedule either the mammogram or the vaccine, Dr. Leung recommends that women inform the facility that they have recently received a COVID-19 vaccine. “Currently, we recommend a follow-up in 4-12 weeks,” she said. “The swelling could subside sooner, perhaps even within 1-2 weeks, but we generally recommend waiting at least 4 weeks to capture the majority of women.”
 

Differences between the vaccines?

The frequency with which axillary adenopathy occurs as a side effect differs with the two COVID-19 vaccines, according to reports from the Centers for Disease Control and Prevention.

For the Moderna vaccine, axillary adenopathy ipsilateral to the vaccination arm was the second most frequently reported local reaction, with 11.6% of recipients aged 18-64 years reporting it after the first dose, and 16.0% reporting it after the second. The average duration of this adenopathy was 1-2 days.

For the Pfizer-BioNTech COVID-19 vaccine, the CDC notes that reports of adenopathy were imbalanced between the vaccine and placebo groups and concluded that adenopathy was plausibly related to the vaccine.

The average duration of adenopathy was approximately 10 days.

Adenopathy was reported within 2-4 days after vaccination for both vaccine groups, the CDC noted.

However, details from the cases reported by Dr. Dodelzon and colleagues paint a somewhat different picture. For example, in case 1, the patient self-detected unilateral axillary adenopathy 9 days after receiving the first dose of the Pfizer-BioNTech vaccine. In case 3, the time between receiving the Moderna vaccine and detection of adenopathy was 13 days.

In both of these cases, the time was much longer than the average duration of 1-2 days noted by the CDC. The authors suggest that in taking the patient’s vaccination history, radiologists understand that the side effect may occur up to several weeks following the COVID-19 vaccination.

In cases 2 and 4, the axillary adenopathy was incidentally noted during mammography, so it is unclear when the onset of this reaction occurred after receiving the COVID-19 vaccine.

The authors and Dr. Leung have disclosed no relevant financial relationships.

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

Axillary adenopathy, or swelling under the armpit, has been reported by women after receiving the Pfizer-BioNTech and Moderna COVID-19 vaccines, but it is also a common symptom of breast cancer.

Clinicians should therefore consider recent COVID-19 vaccination history in the differential diagnosis of patients who present with unilateral axillary adenopathy, according to a new article.

“We noticed an increasing number of patients with swollen lymph nodes on just one side/one underarm who presented for routine screening mammography or ultrasound, and some women who actually felt these swollen nodes,” said author Katerina Dodelzon, MD, assistant professor of clinical radiology at Weill Cornell Medicine, New York.

“Historically, swollen lymph nodes on just one side are relatively rare and are an uncommon occurrence on screening mammography – seen only 0.02%-0.04% of the time – and is a sign that alerts a radiologist to exclude the presence of breast malignancy on that side,” she added.

In an article published in Clinical Imaging, Dr. Dodelzon and colleagues described four cases involving women who received a COVID-19 vaccine and then sought breast screening. In describing these cases, the authors sought “to inform the medical community to consider this benign and self-resolving diagnosis in the setting of what can be alarming presentation of unilateral axillary adenopathy.”

They hope they will decrease unnecessary biopsies and help reassure patients.

Adenopathy has been reported in association with other vaccines, such as the bacille Calmette-Guérin vaccine, influenza vaccines, and the human papillomavirus vaccine, commented Jessica W. T. Leung, MD, president of the Society of Breast Imaging.

“It’s too early to say if there is something different about the COVID-19 vaccines,” said Dr. Leung, who is also professor of diagnostic radiology and deputy chair of breast imaging at the University of Texas MD Anderson Cancer Center, Houston.

“The two vaccines that are currently in use – Pfizer and Moderna – are both mRNA vaccines, and it is unknown if those will give a stronger immune response,” she said. “If the Johnson & Johnson and AstraZeneca vaccines do become available, it will be interesting to see if they elicit as strong a response, since they are not mRNA vaccines. At this time, we have no data to say one way or the other.”

Dr. Leung also noted that these latest vaccine reactions may be getting more attention because “it is COVID-19 related, and everything related to COVID-19 gets more attention.

“It may also be more noticeable because of the large number of people getting vaccinated within a short period of time in an effort to contain the pandemic, and this is not the case with the other vaccines,” she said.
 

New recommendations from SBI

The SBI recently issued recommendations to clinicians that women who experience axillary adenopathy and who have recently been vaccinated on the same side on which the adenopathy occurs be followed for a few weeks to see whether the lymph nodes return to normal, rather than undergo biopsy.

“Many practices are now routinely inquiring about history of recent vaccination and on which side it was given,” Dr. Dodelzon said. She emphasized that women should feel empowered to share that history if they are not asked.

“Letting your mammography technologist or breast imager know that you have recently been vaccinated, and on which side, will provide the breast imager more accurate context within which to interpret the results,” she said.

In addition, the SBI recommends that, if feasible, women schedule routine screening mammography either before the first dose of the COVID-19 vaccine or 4-6 weeks after the second dose to avoid a false-positive finding.

“We want to emphasize that screening mammography is very important, and if possible, to schedule it around the vaccine,” commented Dr. Leung. “But that may not be possible, as most of us don’t have a choice when to get the vaccine.”

If it is not possible to reschedule either the mammogram or the vaccine, Dr. Leung recommends that women inform the facility that they have recently received a COVID-19 vaccine. “Currently, we recommend a follow-up in 4-12 weeks,” she said. “The swelling could subside sooner, perhaps even within 1-2 weeks, but we generally recommend waiting at least 4 weeks to capture the majority of women.”
 

Differences between the vaccines?

The frequency with which axillary adenopathy occurs as a side effect differs with the two COVID-19 vaccines, according to reports from the Centers for Disease Control and Prevention.

For the Moderna vaccine, axillary adenopathy ipsilateral to the vaccination arm was the second most frequently reported local reaction, with 11.6% of recipients aged 18-64 years reporting it after the first dose, and 16.0% reporting it after the second. The average duration of this adenopathy was 1-2 days.

For the Pfizer-BioNTech COVID-19 vaccine, the CDC notes that reports of adenopathy were imbalanced between the vaccine and placebo groups and concluded that adenopathy was plausibly related to the vaccine.

The average duration of adenopathy was approximately 10 days.

Adenopathy was reported within 2-4 days after vaccination for both vaccine groups, the CDC noted.

However, details from the cases reported by Dr. Dodelzon and colleagues paint a somewhat different picture. For example, in case 1, the patient self-detected unilateral axillary adenopathy 9 days after receiving the first dose of the Pfizer-BioNTech vaccine. In case 3, the time between receiving the Moderna vaccine and detection of adenopathy was 13 days.

In both of these cases, the time was much longer than the average duration of 1-2 days noted by the CDC. The authors suggest that in taking the patient’s vaccination history, radiologists understand that the side effect may occur up to several weeks following the COVID-19 vaccination.

In cases 2 and 4, the axillary adenopathy was incidentally noted during mammography, so it is unclear when the onset of this reaction occurred after receiving the COVID-19 vaccine.

The authors and Dr. Leung have disclosed no relevant financial relationships.

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

Axillary adenopathy, or swelling under the armpit, has been reported by women after receiving the Pfizer-BioNTech and Moderna COVID-19 vaccines, but it is also a common symptom of breast cancer.

Clinicians should therefore consider recent COVID-19 vaccination history in the differential diagnosis of patients who present with unilateral axillary adenopathy, according to a new article.

“We noticed an increasing number of patients with swollen lymph nodes on just one side/one underarm who presented for routine screening mammography or ultrasound, and some women who actually felt these swollen nodes,” said author Katerina Dodelzon, MD, assistant professor of clinical radiology at Weill Cornell Medicine, New York.

“Historically, swollen lymph nodes on just one side are relatively rare and are an uncommon occurrence on screening mammography – seen only 0.02%-0.04% of the time – and is a sign that alerts a radiologist to exclude the presence of breast malignancy on that side,” she added.

In an article published in Clinical Imaging, Dr. Dodelzon and colleagues described four cases involving women who received a COVID-19 vaccine and then sought breast screening. In describing these cases, the authors sought “to inform the medical community to consider this benign and self-resolving diagnosis in the setting of what can be alarming presentation of unilateral axillary adenopathy.”

They hope they will decrease unnecessary biopsies and help reassure patients.

Adenopathy has been reported in association with other vaccines, such as the bacille Calmette-Guérin vaccine, influenza vaccines, and the human papillomavirus vaccine, commented Jessica W. T. Leung, MD, president of the Society of Breast Imaging.

“It’s too early to say if there is something different about the COVID-19 vaccines,” said Dr. Leung, who is also professor of diagnostic radiology and deputy chair of breast imaging at the University of Texas MD Anderson Cancer Center, Houston.

“The two vaccines that are currently in use – Pfizer and Moderna – are both mRNA vaccines, and it is unknown if those will give a stronger immune response,” she said. “If the Johnson & Johnson and AstraZeneca vaccines do become available, it will be interesting to see if they elicit as strong a response, since they are not mRNA vaccines. At this time, we have no data to say one way or the other.”

Dr. Leung also noted that these latest vaccine reactions may be getting more attention because “it is COVID-19 related, and everything related to COVID-19 gets more attention.

“It may also be more noticeable because of the large number of people getting vaccinated within a short period of time in an effort to contain the pandemic, and this is not the case with the other vaccines,” she said.
 

New recommendations from SBI

The SBI recently issued recommendations to clinicians that women who experience axillary adenopathy and who have recently been vaccinated on the same side on which the adenopathy occurs be followed for a few weeks to see whether the lymph nodes return to normal, rather than undergo biopsy.

“Many practices are now routinely inquiring about history of recent vaccination and on which side it was given,” Dr. Dodelzon said. She emphasized that women should feel empowered to share that history if they are not asked.

“Letting your mammography technologist or breast imager know that you have recently been vaccinated, and on which side, will provide the breast imager more accurate context within which to interpret the results,” she said.

In addition, the SBI recommends that, if feasible, women schedule routine screening mammography either before the first dose of the COVID-19 vaccine or 4-6 weeks after the second dose to avoid a false-positive finding.

“We want to emphasize that screening mammography is very important, and if possible, to schedule it around the vaccine,” commented Dr. Leung. “But that may not be possible, as most of us don’t have a choice when to get the vaccine.”

If it is not possible to reschedule either the mammogram or the vaccine, Dr. Leung recommends that women inform the facility that they have recently received a COVID-19 vaccine. “Currently, we recommend a follow-up in 4-12 weeks,” she said. “The swelling could subside sooner, perhaps even within 1-2 weeks, but we generally recommend waiting at least 4 weeks to capture the majority of women.”
 

Differences between the vaccines?

The frequency with which axillary adenopathy occurs as a side effect differs with the two COVID-19 vaccines, according to reports from the Centers for Disease Control and Prevention.

For the Moderna vaccine, axillary adenopathy ipsilateral to the vaccination arm was the second most frequently reported local reaction, with 11.6% of recipients aged 18-64 years reporting it after the first dose, and 16.0% reporting it after the second. The average duration of this adenopathy was 1-2 days.

For the Pfizer-BioNTech COVID-19 vaccine, the CDC notes that reports of adenopathy were imbalanced between the vaccine and placebo groups and concluded that adenopathy was plausibly related to the vaccine.

The average duration of adenopathy was approximately 10 days.

Adenopathy was reported within 2-4 days after vaccination for both vaccine groups, the CDC noted.

However, details from the cases reported by Dr. Dodelzon and colleagues paint a somewhat different picture. For example, in case 1, the patient self-detected unilateral axillary adenopathy 9 days after receiving the first dose of the Pfizer-BioNTech vaccine. In case 3, the time between receiving the Moderna vaccine and detection of adenopathy was 13 days.

In both of these cases, the time was much longer than the average duration of 1-2 days noted by the CDC. The authors suggest that in taking the patient’s vaccination history, radiologists understand that the side effect may occur up to several weeks following the COVID-19 vaccination.

In cases 2 and 4, the axillary adenopathy was incidentally noted during mammography, so it is unclear when the onset of this reaction occurred after receiving the COVID-19 vaccine.

The authors and Dr. Leung have disclosed no relevant financial relationships.

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

Phase 3 trial results suggest durvalumab (Imfinzi) does not improve overall survival in unresectable metastatic bladder cancer, so the drug will no longer be approved to treat this patient population in the United States, according to an announcement from AstraZeneca.

The change does not affect this indication outside the United States, nor does it affect other approved durvalumab indications within the United States.

For example, durvalumab remains approved by the Food and Drug Administration in the curative-intent setting of unresectable, stage III non–small cell lung cancer after chemoradiotherapy and for the treatment of extensive-stage small cell lung cancer.

AstraZeneca is continuing with clinical trials of durvalumab in various combinations for the treatment of bladder cancer.
 

Granted accelerated approval

Durvalumab was granted accelerated approval in May 2017 by the FDA specifically for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing chemotherapy or who experience disease progression within 12 months of neoadjuvant or adjuvant treatment with that chemotherapy.

That accelerated approval was based on the surrogate markers of tumor response rate and duration of response from Study 1108, a phase 1/2 trial. In this trial, the overall response rate was 17.8% in a cohort of 191 patients with locally advanced or metastatic urothelial cancer that had progressed during or after a platinum-based regimen.

However, in the confirmatory phase 3 DANUBE trial in patients with unresectable metastatic bladder cancer, neither durvalumab nor durvalumab plus tremelimumab met the primary endpoint of improving overall survival in comparison with standard-of-care chemotherapy.

“While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded,” Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, said in a company press statement.

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

Phase 3 trial results suggest durvalumab (Imfinzi) does not improve overall survival in unresectable metastatic bladder cancer, so the drug will no longer be approved to treat this patient population in the United States, according to an announcement from AstraZeneca.

The change does not affect this indication outside the United States, nor does it affect other approved durvalumab indications within the United States.

For example, durvalumab remains approved by the Food and Drug Administration in the curative-intent setting of unresectable, stage III non–small cell lung cancer after chemoradiotherapy and for the treatment of extensive-stage small cell lung cancer.

AstraZeneca is continuing with clinical trials of durvalumab in various combinations for the treatment of bladder cancer.
 

Granted accelerated approval

Durvalumab was granted accelerated approval in May 2017 by the FDA specifically for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing chemotherapy or who experience disease progression within 12 months of neoadjuvant or adjuvant treatment with that chemotherapy.

That accelerated approval was based on the surrogate markers of tumor response rate and duration of response from Study 1108, a phase 1/2 trial. In this trial, the overall response rate was 17.8% in a cohort of 191 patients with locally advanced or metastatic urothelial cancer that had progressed during or after a platinum-based regimen.

However, in the confirmatory phase 3 DANUBE trial in patients with unresectable metastatic bladder cancer, neither durvalumab nor durvalumab plus tremelimumab met the primary endpoint of improving overall survival in comparison with standard-of-care chemotherapy.

“While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded,” Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, said in a company press statement.

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

Phase 3 trial results suggest durvalumab (Imfinzi) does not improve overall survival in unresectable metastatic bladder cancer, so the drug will no longer be approved to treat this patient population in the United States, according to an announcement from AstraZeneca.

The change does not affect this indication outside the United States, nor does it affect other approved durvalumab indications within the United States.

For example, durvalumab remains approved by the Food and Drug Administration in the curative-intent setting of unresectable, stage III non–small cell lung cancer after chemoradiotherapy and for the treatment of extensive-stage small cell lung cancer.

AstraZeneca is continuing with clinical trials of durvalumab in various combinations for the treatment of bladder cancer.
 

Granted accelerated approval

Durvalumab was granted accelerated approval in May 2017 by the FDA specifically for the treatment of patients with locally advanced or metastatic urothelial carcinoma who experience disease progression during or following platinum-containing chemotherapy or who experience disease progression within 12 months of neoadjuvant or adjuvant treatment with that chemotherapy.

That accelerated approval was based on the surrogate markers of tumor response rate and duration of response from Study 1108, a phase 1/2 trial. In this trial, the overall response rate was 17.8% in a cohort of 191 patients with locally advanced or metastatic urothelial cancer that had progressed during or after a platinum-based regimen.

However, in the confirmatory phase 3 DANUBE trial in patients with unresectable metastatic bladder cancer, neither durvalumab nor durvalumab plus tremelimumab met the primary endpoint of improving overall survival in comparison with standard-of-care chemotherapy.

“While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded,” Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, said in a company press statement.

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

A new artificial intelligence (AI) program can effectively identify potential melanoma in wide-field photos, researchers say.

The system could use photographs of large areas of patients’ bodies taken with ordinary cameras in primary care or by the patients themselves to screen for early-stage melanoma, said Luis R. Soenksen, PhD, a postdoctoral associate and venture builder at Massachusetts Institute of Technology in Cambridge, Mass.

“We believe we’re providing technology for that to happen at a massive scale, which is what is needed to reduce mortality rates,” he said in an interview.

He and his colleagues published their findings in Science Translational Medicine.

Diagnosing skin lesions has already proved one of the most promising medical applications of AI. In a 2017 paper, researchers reported that a deep neural network had classified skin lesions more accurately than did dermatologists. But so far, most such programs depend on experts to preselect the lesions worthy of analysis. And they use images from dermoscopy or single-lesion near-field photography.

Dr. Soenksen and colleagues wanted a system that could use a variety of cameras such as those in smartphones under a variety of conditions to assess lesions over wide areas of anatomy.

So they programmed their convolutional neural network to simultaneously use two approaches for screening lesions. Like the earlier systems, theirs looks for characteristics of individual lesions, such as asymmetry, border unevenness, color distribution, diameter, and evolution (ABCDE.) But it also looks for lesion saliency, a comparison of the lesions on the skin of one individual to identify the “ugly ducklings” that stand out from the rest.

They trained the system using 20,388 wide-field images from 133 patients at the Hospital Gregorio Marañón in Madrid, as well as publicly available images. The images were taken with a variety of consumer-grade cameras, about half of them nondermoscopy, and included backgrounds, skin edges, bare skin sections, nonsuspicious pigmented lesions, and suspicious pigmented lesions. The lesions in the images were visually classified by a consensus of three board-certified dermatologists.

Once they trained the system, the researchers tested it on another 6,796 images from the same patients, using the dermatologists’ classification as the gold standard. The system distinguished the suspicious lesions with 90.3% sensitivity (true positive), 89.9% specificity (true negative), and 86.56% accuracy.

Dr. Soenksen said he could envision photos acquired for screening in three scenarios. First, people could photograph themselves, or someone else at their homes could photograph them. These photos could even include whole nude bodies.

Second, clinicians could photograph patients’ body parts during medical visits for other purposes. “It makes sense to do these evaluations in the point of care where a referral can actually happen, like the primary care office,” said Dr. Soenksen.

Third, photos could be taken at places where people show up in bathing suits.

In each scenario, the system would then tell patients whether any lesions needed evaluation by a dermatologist.

To ensure privacy, Dr. Soenksen envisions using devices that do not transmit all the data to the cloud but instead do at least some of the calculations on their own. High-end smartphones have sufficient computing capacity for that, he said.

In their next phase of this work, the researchers would like to test the system on more skin of color cases and in more varied conditions, said Dr. Soenksen. And they would like to put it through randomized clinical trials, potentially using biopsies to validate the results.

That’s a key step, said Veronica Rotemberg, MD, PhD, director of the dermatology imaging informatics program at Memorial Sloan Kettering Cancer Center, New York.

“Usually when we think about melanoma, we think of histology as the gold standard, or specific subtypes of melanoma as a gold standard,” she said in an interview.

The technology also raises the question of excessive screening, she said. “Identifying the ugly duckling could be extremely important in finding more melanoma,” she said. “But in a patient who doesn’t have melanoma, it could lead to a lot of unnecessary biopsies.”

The sheer number of referrals generated by such a system could overwhelm the dermatologists assigned to follow up on them, she added.

Still, Dr. Rotemberg said, the study is “a good proof of concept.” Ugly duckling analysis is a very active area of AI research with thousands of teams of researchers worldwide working on systems similar to this one, she added. “I’m so excited for the authors.”

Neither Dr. Soenksen nor Dr. Rotemberg disclosed any relevant financial interests.
 

A new artificial intelligence (AI) program can effectively identify potential melanoma in wide-field photos, researchers say.

The system could use photographs of large areas of patients’ bodies taken with ordinary cameras in primary care or by the patients themselves to screen for early-stage melanoma, said Luis R. Soenksen, PhD, a postdoctoral associate and venture builder at Massachusetts Institute of Technology in Cambridge, Mass.

“We believe we’re providing technology for that to happen at a massive scale, which is what is needed to reduce mortality rates,” he said in an interview.

He and his colleagues published their findings in Science Translational Medicine.

Diagnosing skin lesions has already proved one of the most promising medical applications of AI. In a 2017 paper, researchers reported that a deep neural network had classified skin lesions more accurately than did dermatologists. But so far, most such programs depend on experts to preselect the lesions worthy of analysis. And they use images from dermoscopy or single-lesion near-field photography.

Dr. Soenksen and colleagues wanted a system that could use a variety of cameras such as those in smartphones under a variety of conditions to assess lesions over wide areas of anatomy.

So they programmed their convolutional neural network to simultaneously use two approaches for screening lesions. Like the earlier systems, theirs looks for characteristics of individual lesions, such as asymmetry, border unevenness, color distribution, diameter, and evolution (ABCDE.) But it also looks for lesion saliency, a comparison of the lesions on the skin of one individual to identify the “ugly ducklings” that stand out from the rest.

They trained the system using 20,388 wide-field images from 133 patients at the Hospital Gregorio Marañón in Madrid, as well as publicly available images. The images were taken with a variety of consumer-grade cameras, about half of them nondermoscopy, and included backgrounds, skin edges, bare skin sections, nonsuspicious pigmented lesions, and suspicious pigmented lesions. The lesions in the images were visually classified by a consensus of three board-certified dermatologists.

Once they trained the system, the researchers tested it on another 6,796 images from the same patients, using the dermatologists’ classification as the gold standard. The system distinguished the suspicious lesions with 90.3% sensitivity (true positive), 89.9% specificity (true negative), and 86.56% accuracy.

Dr. Soenksen said he could envision photos acquired for screening in three scenarios. First, people could photograph themselves, or someone else at their homes could photograph them. These photos could even include whole nude bodies.

Second, clinicians could photograph patients’ body parts during medical visits for other purposes. “It makes sense to do these evaluations in the point of care where a referral can actually happen, like the primary care office,” said Dr. Soenksen.

Third, photos could be taken at places where people show up in bathing suits.

In each scenario, the system would then tell patients whether any lesions needed evaluation by a dermatologist.

To ensure privacy, Dr. Soenksen envisions using devices that do not transmit all the data to the cloud but instead do at least some of the calculations on their own. High-end smartphones have sufficient computing capacity for that, he said.

In their next phase of this work, the researchers would like to test the system on more skin of color cases and in more varied conditions, said Dr. Soenksen. And they would like to put it through randomized clinical trials, potentially using biopsies to validate the results.

That’s a key step, said Veronica Rotemberg, MD, PhD, director of the dermatology imaging informatics program at Memorial Sloan Kettering Cancer Center, New York.

“Usually when we think about melanoma, we think of histology as the gold standard, or specific subtypes of melanoma as a gold standard,” she said in an interview.

The technology also raises the question of excessive screening, she said. “Identifying the ugly duckling could be extremely important in finding more melanoma,” she said. “But in a patient who doesn’t have melanoma, it could lead to a lot of unnecessary biopsies.”

The sheer number of referrals generated by such a system could overwhelm the dermatologists assigned to follow up on them, she added.

Still, Dr. Rotemberg said, the study is “a good proof of concept.” Ugly duckling analysis is a very active area of AI research with thousands of teams of researchers worldwide working on systems similar to this one, she added. “I’m so excited for the authors.”

Neither Dr. Soenksen nor Dr. Rotemberg disclosed any relevant financial interests.
 

A new artificial intelligence (AI) program can effectively identify potential melanoma in wide-field photos, researchers say.

The system could use photographs of large areas of patients’ bodies taken with ordinary cameras in primary care or by the patients themselves to screen for early-stage melanoma, said Luis R. Soenksen, PhD, a postdoctoral associate and venture builder at Massachusetts Institute of Technology in Cambridge, Mass.

“We believe we’re providing technology for that to happen at a massive scale, which is what is needed to reduce mortality rates,” he said in an interview.

He and his colleagues published their findings in Science Translational Medicine.

Diagnosing skin lesions has already proved one of the most promising medical applications of AI. In a 2017 paper, researchers reported that a deep neural network had classified skin lesions more accurately than did dermatologists. But so far, most such programs depend on experts to preselect the lesions worthy of analysis. And they use images from dermoscopy or single-lesion near-field photography.

Dr. Soenksen and colleagues wanted a system that could use a variety of cameras such as those in smartphones under a variety of conditions to assess lesions over wide areas of anatomy.

So they programmed their convolutional neural network to simultaneously use two approaches for screening lesions. Like the earlier systems, theirs looks for characteristics of individual lesions, such as asymmetry, border unevenness, color distribution, diameter, and evolution (ABCDE.) But it also looks for lesion saliency, a comparison of the lesions on the skin of one individual to identify the “ugly ducklings” that stand out from the rest.

They trained the system using 20,388 wide-field images from 133 patients at the Hospital Gregorio Marañón in Madrid, as well as publicly available images. The images were taken with a variety of consumer-grade cameras, about half of them nondermoscopy, and included backgrounds, skin edges, bare skin sections, nonsuspicious pigmented lesions, and suspicious pigmented lesions. The lesions in the images were visually classified by a consensus of three board-certified dermatologists.

Once they trained the system, the researchers tested it on another 6,796 images from the same patients, using the dermatologists’ classification as the gold standard. The system distinguished the suspicious lesions with 90.3% sensitivity (true positive), 89.9% specificity (true negative), and 86.56% accuracy.

Dr. Soenksen said he could envision photos acquired for screening in three scenarios. First, people could photograph themselves, or someone else at their homes could photograph them. These photos could even include whole nude bodies.

Second, clinicians could photograph patients’ body parts during medical visits for other purposes. “It makes sense to do these evaluations in the point of care where a referral can actually happen, like the primary care office,” said Dr. Soenksen.

Third, photos could be taken at places where people show up in bathing suits.

In each scenario, the system would then tell patients whether any lesions needed evaluation by a dermatologist.

To ensure privacy, Dr. Soenksen envisions using devices that do not transmit all the data to the cloud but instead do at least some of the calculations on their own. High-end smartphones have sufficient computing capacity for that, he said.

In their next phase of this work, the researchers would like to test the system on more skin of color cases and in more varied conditions, said Dr. Soenksen. And they would like to put it through randomized clinical trials, potentially using biopsies to validate the results.

That’s a key step, said Veronica Rotemberg, MD, PhD, director of the dermatology imaging informatics program at Memorial Sloan Kettering Cancer Center, New York.

“Usually when we think about melanoma, we think of histology as the gold standard, or specific subtypes of melanoma as a gold standard,” she said in an interview.

The technology also raises the question of excessive screening, she said. “Identifying the ugly duckling could be extremely important in finding more melanoma,” she said. “But in a patient who doesn’t have melanoma, it could lead to a lot of unnecessary biopsies.”

The sheer number of referrals generated by such a system could overwhelm the dermatologists assigned to follow up on them, she added.

Still, Dr. Rotemberg said, the study is “a good proof of concept.” Ugly duckling analysis is a very active area of AI research with thousands of teams of researchers worldwide working on systems similar to this one, she added. “I’m so excited for the authors.”

Neither Dr. Soenksen nor Dr. Rotemberg disclosed any relevant financial interests.
 

Two new approaches to surveillance imaging after treatment of stage I testicular seminoma sharply reduce or eliminate radiation exposure relative to the standard approach, without substantially compromising relapse detection, the phase 3 TRISST study suggests.

Results were reported at the 2021 Genitourinary Cancers Symposium (Abstract 374).

“Stage I seminoma has a survival that approaches 100%. Over recent years, CT surveillance has become an international standard of care and has largely replaced the use of adjuvant treatment,” said investigator Robert A. Huddart, MRCP, FRCR, PhD, of The Royal Marsden NHS Foundation Trust, London.

“A typical surveillance protocol, however, consists of multiple CT scans taken over a period of a few years and results in quite a high diagnostic radiation dose, which has raised questions about the long-term risk of second malignancies related to this program,” he noted. “At the moment, there is no evidence base to inform how frequently imaging should be undertaken and the type of imaging that should be used.”

Results of TRISST showed that, with a median 6-year follow-up during which men were monitored with various surveillance protocols, 1.5% experienced a relapse that was advanced (stage IIC or higher) at detection.

The incidence of relapse was 0.3% with the standard schedule of seven abdominal surveillance scans and a statistically noninferior 2.8% with three more widely spaced scans. Also, compared with the standard CT scans, which yielded an incidence of 2.6%, MRI scans were noninferior, yielding an incidence of 0.6%.

“The three-scan schedule was noninferior to seven scans in our protocol, and in fact, with the three-scan schedule, we would use over 1,000 fewer scans at a cost of perhaps having four relapses that could have been avoided,” Dr. Huddart pointed out. “We can conclude that MRI is noninferior to CT and should be recommended to avoid irradiation. This study will provide an evidence base for making the transition to MRI, which is important. The MRI scan is more complex – it takes longer and is more resource heavy. So we do need to supply the evidence that it is the right thing to do for patients.”

Need for expertise in interpreting MRI scans is a valid concern, he acknowledged. “There is a degree of specialization in the UK for testis cancer management, and clearly, you had to be specialist to take part in the study. So I can’t say it is your everyday radiologist, but the data would suggest we actually saw less errors in terms of pickup with the MRI scan than with the CT scan,” he said. “You do need to have a level of expertise, but it doesn’t require super-specialist expertise. I suppose that will be a learning lesson for all of us, to learn better MRI interpretation if we are using MRI.”
 

Trial details

The 669 men randomized in TRISST (NCT00589537), a multicenter trial with a factorial and noninferiority design, had undergone orchiectomy for stage I seminoma and did not have any adjuvant therapy planned.

They were randomized once on number of surveillance scans: seven scans (at 6, 12, 18, 24, 36, 48, and 60 months) vs. three scans (at 6, 18, and 36 months). And they were randomized again on scan modality: CT versus MRI. All groups had similar follow-up otherwise, consisting of periodic chest radiographs, tumor marker tests, and clinical assessments.

The primary outcome, 6-year incidence of advanced relapse defined as stage IIC or higher (i.e., measuring 5 cm or greater) by Royal Marsden Hospital criteria, was chosen because, when the study began, this was the dividing point between using local therapy and using systemic multiagent chemotherapy to treat a relapse, Dr. Huddart explained.

Among men remaining on surveillance, compliance was good, with 94% of all scans attended and 79% performed on time, he reported.

Overall, 12% of the randomized population experienced a relapse of any stage during follow-up, with nearly all relapses occurring within the first 3 years.

The 6-year incidence of advanced relapse was just 1.5% in the entire trial population, lower than the 5.7% expected in trial planning, according to Dr. Huddart.

In intention-to-treat analyses, the incidence was 2.8% with the three-scan schedule and 0.3% with the seven-scan schedule, with the difference of 2.6% and the bounds of the 90% confidence interval falling within the predefined noninferiority margin of 5.7%.

Using three scans instead of seven scans increased the proportion of patients with relapse who had advanced stage from 3% to 20%. Four of the nine advanced relapses occurring with the three-scan schedule could possibly have been detected earlier with the seven-scan schedule.

The 6-year incidence of advanced relapse was 0.6% with MRI scans and 2.6% with CT scans. The difference of –1.9% and the bounds of the 90% confidence interval fell within the noninferiority margin. Use of MRI instead of CT reduced the proportion of patients with relapse who had advanced stage from 20% to 5%.

For both the scan frequency comparison and the scan modality comparison, findings were essentially the same in per protocol analyses and in analyses that instead looked at relapses measuring 3 cm or greater, according to Dr. Huddart.

Fully 89% of patients with advanced relapses were treated with chemotherapy only, and 56% of all patients with advanced relapse had a response to their treatment.

Most patients experiencing a relapse of any stage, 93%, were alive and free of disease at their most recent follow-up, Dr. Huddart reported. Overall survival for the trial population was 99% and similar across surveillance groups, with no deaths due to testicular cancer.
 

Risk-tailored surveillance

“Noninferiority trials are much more challenging than equivalence or superiority trials,” observed invited discussant Pilar Laguna, MD, PhD, of Istanbul Medipol University, Turkey.

She expressed some reservations about TRISST results, including the much lower than expected incidence of advanced relapse, which may have affected comparisons, and problematic compliance, as about one-quarter of patients stopped surveillance before relapse or withdrew from the trial before 6 years of follow-up.

Recurrence after treatment of stage I seminoma is largely driven by the risk factors of tumor size exceeding 4 cm and presence of rete testis invasion, and 54% of TRISST patients did not have either of these factors, Dr. Laguna noted.

“While a more relaxed schedule may well suit those patients at low risk, more intense schedules will be appropriate for patients with risk factors,” she maintained. “I am pretty sure that the TRISST trial will impact future guideline recommendations, although still I think that one approach may not fit all.”

TRISST was funded by Cancer Research UK and the MRC Clinical Trials Unit. Dr. Huddart disclosed relationships with Janssen Oncology, Bayer, Bristol-Myers Squibb, Merck Sharp & Dohme, Nektar, and Roche. Dr. Laguna disclosed that she is chair of the EAU Testicular Cancer Guidelines Panel.

Two new approaches to surveillance imaging after treatment of stage I testicular seminoma sharply reduce or eliminate radiation exposure relative to the standard approach, without substantially compromising relapse detection, the phase 3 TRISST study suggests.

Results were reported at the 2021 Genitourinary Cancers Symposium (Abstract 374).

“Stage I seminoma has a survival that approaches 100%. Over recent years, CT surveillance has become an international standard of care and has largely replaced the use of adjuvant treatment,” said investigator Robert A. Huddart, MRCP, FRCR, PhD, of The Royal Marsden NHS Foundation Trust, London.

“A typical surveillance protocol, however, consists of multiple CT scans taken over a period of a few years and results in quite a high diagnostic radiation dose, which has raised questions about the long-term risk of second malignancies related to this program,” he noted. “At the moment, there is no evidence base to inform how frequently imaging should be undertaken and the type of imaging that should be used.”

Results of TRISST showed that, with a median 6-year follow-up during which men were monitored with various surveillance protocols, 1.5% experienced a relapse that was advanced (stage IIC or higher) at detection.

The incidence of relapse was 0.3% with the standard schedule of seven abdominal surveillance scans and a statistically noninferior 2.8% with three more widely spaced scans. Also, compared with the standard CT scans, which yielded an incidence of 2.6%, MRI scans were noninferior, yielding an incidence of 0.6%.

“The three-scan schedule was noninferior to seven scans in our protocol, and in fact, with the three-scan schedule, we would use over 1,000 fewer scans at a cost of perhaps having four relapses that could have been avoided,” Dr. Huddart pointed out. “We can conclude that MRI is noninferior to CT and should be recommended to avoid irradiation. This study will provide an evidence base for making the transition to MRI, which is important. The MRI scan is more complex – it takes longer and is more resource heavy. So we do need to supply the evidence that it is the right thing to do for patients.”

Need for expertise in interpreting MRI scans is a valid concern, he acknowledged. “There is a degree of specialization in the UK for testis cancer management, and clearly, you had to be specialist to take part in the study. So I can’t say it is your everyday radiologist, but the data would suggest we actually saw less errors in terms of pickup with the MRI scan than with the CT scan,” he said. “You do need to have a level of expertise, but it doesn’t require super-specialist expertise. I suppose that will be a learning lesson for all of us, to learn better MRI interpretation if we are using MRI.”
 

Trial details

The 669 men randomized in TRISST (NCT00589537), a multicenter trial with a factorial and noninferiority design, had undergone orchiectomy for stage I seminoma and did not have any adjuvant therapy planned.

They were randomized once on number of surveillance scans: seven scans (at 6, 12, 18, 24, 36, 48, and 60 months) vs. three scans (at 6, 18, and 36 months). And they were randomized again on scan modality: CT versus MRI. All groups had similar follow-up otherwise, consisting of periodic chest radiographs, tumor marker tests, and clinical assessments.

The primary outcome, 6-year incidence of advanced relapse defined as stage IIC or higher (i.e., measuring 5 cm or greater) by Royal Marsden Hospital criteria, was chosen because, when the study began, this was the dividing point between using local therapy and using systemic multiagent chemotherapy to treat a relapse, Dr. Huddart explained.

Among men remaining on surveillance, compliance was good, with 94% of all scans attended and 79% performed on time, he reported.

Overall, 12% of the randomized population experienced a relapse of any stage during follow-up, with nearly all relapses occurring within the first 3 years.

The 6-year incidence of advanced relapse was just 1.5% in the entire trial population, lower than the 5.7% expected in trial planning, according to Dr. Huddart.

In intention-to-treat analyses, the incidence was 2.8% with the three-scan schedule and 0.3% with the seven-scan schedule, with the difference of 2.6% and the bounds of the 90% confidence interval falling within the predefined noninferiority margin of 5.7%.

Using three scans instead of seven scans increased the proportion of patients with relapse who had advanced stage from 3% to 20%. Four of the nine advanced relapses occurring with the three-scan schedule could possibly have been detected earlier with the seven-scan schedule.

The 6-year incidence of advanced relapse was 0.6% with MRI scans and 2.6% with CT scans. The difference of –1.9% and the bounds of the 90% confidence interval fell within the noninferiority margin. Use of MRI instead of CT reduced the proportion of patients with relapse who had advanced stage from 20% to 5%.

For both the scan frequency comparison and the scan modality comparison, findings were essentially the same in per protocol analyses and in analyses that instead looked at relapses measuring 3 cm or greater, according to Dr. Huddart.

Fully 89% of patients with advanced relapses were treated with chemotherapy only, and 56% of all patients with advanced relapse had a response to their treatment.

Most patients experiencing a relapse of any stage, 93%, were alive and free of disease at their most recent follow-up, Dr. Huddart reported. Overall survival for the trial population was 99% and similar across surveillance groups, with no deaths due to testicular cancer.
 

Risk-tailored surveillance

“Noninferiority trials are much more challenging than equivalence or superiority trials,” observed invited discussant Pilar Laguna, MD, PhD, of Istanbul Medipol University, Turkey.

She expressed some reservations about TRISST results, including the much lower than expected incidence of advanced relapse, which may have affected comparisons, and problematic compliance, as about one-quarter of patients stopped surveillance before relapse or withdrew from the trial before 6 years of follow-up.

Recurrence after treatment of stage I seminoma is largely driven by the risk factors of tumor size exceeding 4 cm and presence of rete testis invasion, and 54% of TRISST patients did not have either of these factors, Dr. Laguna noted.

“While a more relaxed schedule may well suit those patients at low risk, more intense schedules will be appropriate for patients with risk factors,” she maintained. “I am pretty sure that the TRISST trial will impact future guideline recommendations, although still I think that one approach may not fit all.”

TRISST was funded by Cancer Research UK and the MRC Clinical Trials Unit. Dr. Huddart disclosed relationships with Janssen Oncology, Bayer, Bristol-Myers Squibb, Merck Sharp & Dohme, Nektar, and Roche. Dr. Laguna disclosed that she is chair of the EAU Testicular Cancer Guidelines Panel.

Two new approaches to surveillance imaging after treatment of stage I testicular seminoma sharply reduce or eliminate radiation exposure relative to the standard approach, without substantially compromising relapse detection, the phase 3 TRISST study suggests.

Results were reported at the 2021 Genitourinary Cancers Symposium (Abstract 374).

“Stage I seminoma has a survival that approaches 100%. Over recent years, CT surveillance has become an international standard of care and has largely replaced the use of adjuvant treatment,” said investigator Robert A. Huddart, MRCP, FRCR, PhD, of The Royal Marsden NHS Foundation Trust, London.

“A typical surveillance protocol, however, consists of multiple CT scans taken over a period of a few years and results in quite a high diagnostic radiation dose, which has raised questions about the long-term risk of second malignancies related to this program,” he noted. “At the moment, there is no evidence base to inform how frequently imaging should be undertaken and the type of imaging that should be used.”

Results of TRISST showed that, with a median 6-year follow-up during which men were monitored with various surveillance protocols, 1.5% experienced a relapse that was advanced (stage IIC or higher) at detection.

The incidence of relapse was 0.3% with the standard schedule of seven abdominal surveillance scans and a statistically noninferior 2.8% with three more widely spaced scans. Also, compared with the standard CT scans, which yielded an incidence of 2.6%, MRI scans were noninferior, yielding an incidence of 0.6%.

“The three-scan schedule was noninferior to seven scans in our protocol, and in fact, with the three-scan schedule, we would use over 1,000 fewer scans at a cost of perhaps having four relapses that could have been avoided,” Dr. Huddart pointed out. “We can conclude that MRI is noninferior to CT and should be recommended to avoid irradiation. This study will provide an evidence base for making the transition to MRI, which is important. The MRI scan is more complex – it takes longer and is more resource heavy. So we do need to supply the evidence that it is the right thing to do for patients.”

Need for expertise in interpreting MRI scans is a valid concern, he acknowledged. “There is a degree of specialization in the UK for testis cancer management, and clearly, you had to be specialist to take part in the study. So I can’t say it is your everyday radiologist, but the data would suggest we actually saw less errors in terms of pickup with the MRI scan than with the CT scan,” he said. “You do need to have a level of expertise, but it doesn’t require super-specialist expertise. I suppose that will be a learning lesson for all of us, to learn better MRI interpretation if we are using MRI.”
 

Trial details

The 669 men randomized in TRISST (NCT00589537), a multicenter trial with a factorial and noninferiority design, had undergone orchiectomy for stage I seminoma and did not have any adjuvant therapy planned.

They were randomized once on number of surveillance scans: seven scans (at 6, 12, 18, 24, 36, 48, and 60 months) vs. three scans (at 6, 18, and 36 months). And they were randomized again on scan modality: CT versus MRI. All groups had similar follow-up otherwise, consisting of periodic chest radiographs, tumor marker tests, and clinical assessments.

The primary outcome, 6-year incidence of advanced relapse defined as stage IIC or higher (i.e., measuring 5 cm or greater) by Royal Marsden Hospital criteria, was chosen because, when the study began, this was the dividing point between using local therapy and using systemic multiagent chemotherapy to treat a relapse, Dr. Huddart explained.

Among men remaining on surveillance, compliance was good, with 94% of all scans attended and 79% performed on time, he reported.

Overall, 12% of the randomized population experienced a relapse of any stage during follow-up, with nearly all relapses occurring within the first 3 years.

The 6-year incidence of advanced relapse was just 1.5% in the entire trial population, lower than the 5.7% expected in trial planning, according to Dr. Huddart.

In intention-to-treat analyses, the incidence was 2.8% with the three-scan schedule and 0.3% with the seven-scan schedule, with the difference of 2.6% and the bounds of the 90% confidence interval falling within the predefined noninferiority margin of 5.7%.

Using three scans instead of seven scans increased the proportion of patients with relapse who had advanced stage from 3% to 20%. Four of the nine advanced relapses occurring with the three-scan schedule could possibly have been detected earlier with the seven-scan schedule.

The 6-year incidence of advanced relapse was 0.6% with MRI scans and 2.6% with CT scans. The difference of –1.9% and the bounds of the 90% confidence interval fell within the noninferiority margin. Use of MRI instead of CT reduced the proportion of patients with relapse who had advanced stage from 20% to 5%.

For both the scan frequency comparison and the scan modality comparison, findings were essentially the same in per protocol analyses and in analyses that instead looked at relapses measuring 3 cm or greater, according to Dr. Huddart.

Fully 89% of patients with advanced relapses were treated with chemotherapy only, and 56% of all patients with advanced relapse had a response to their treatment.

Most patients experiencing a relapse of any stage, 93%, were alive and free of disease at their most recent follow-up, Dr. Huddart reported. Overall survival for the trial population was 99% and similar across surveillance groups, with no deaths due to testicular cancer.
 

Risk-tailored surveillance

“Noninferiority trials are much more challenging than equivalence or superiority trials,” observed invited discussant Pilar Laguna, MD, PhD, of Istanbul Medipol University, Turkey.

She expressed some reservations about TRISST results, including the much lower than expected incidence of advanced relapse, which may have affected comparisons, and problematic compliance, as about one-quarter of patients stopped surveillance before relapse or withdrew from the trial before 6 years of follow-up.

Recurrence after treatment of stage I seminoma is largely driven by the risk factors of tumor size exceeding 4 cm and presence of rete testis invasion, and 54% of TRISST patients did not have either of these factors, Dr. Laguna noted.

“While a more relaxed schedule may well suit those patients at low risk, more intense schedules will be appropriate for patients with risk factors,” she maintained. “I am pretty sure that the TRISST trial will impact future guideline recommendations, although still I think that one approach may not fit all.”

TRISST was funded by Cancer Research UK and the MRC Clinical Trials Unit. Dr. Huddart disclosed relationships with Janssen Oncology, Bayer, Bristol-Myers Squibb, Merck Sharp & Dohme, Nektar, and Roche. Dr. Laguna disclosed that she is chair of the EAU Testicular Cancer Guidelines Panel.

The Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) for the treatment of advanced non–small cell lung cancer (NSCLC).

Specifically, the indication is for first-line treatment as monotherapy for patients with locally advanced or metastatic disease who are not candidates for surgical resection or definitive chemoradiotherapy and whose tumors have a high expression of programmed death–ligand 1 (PD-L1) (Tumor Proportion Score >50%), as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations.

This is the third indication for cemiplimab-rlwc, a monoclonal antibody and PD-1 inhibitor.

In February, it was approved as the first immunotherapy to treat patients with locally advanced or metastatic basal cell carcinoma that was previously treated with a hedgehog pathway inhibitor or for whom a hedgehog inhibitor is inappropriate.

Cemiplimab-rlwc previously received FDA approval in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma for patients who were not eligible for curative surgery or radiotherapy. At the time, Karl Lewis, MD, a professor at the University of Colorado at Denver, Aurora, and a trial investigator, predicted that the drug “will change the treatment paradigm for patients with advanced basal cell carcinoma.”
 

Outperforms chemotherapy

The approval for use in NSCLC is based on results from the phase 3, open-label EMPOWER-Lung 1 trial, which randomly assigned 710 patients in a 1:1 ratio to receive either cemiplimab-rwlc or platinum-doublet chemotherapy. Patients had either locally advanced NSCLC and were not candidates for surgical resection or definitive chemoradiotherapy, or they had metastatic NSCLC.

Patients in the experimental arm received cemiplimab-rwlc 350 mg intravenously every 3 weeks. The primary efficacy outcome measures were overall survival (OS) and progression-free survival (PFS), determined on the basis of blinded independent central review.

Results showed statistically significant improvements in both outcomes. Median OS was 22.1 months with cemiplimab-rwlc versus 14.3 months with chemotherapy (hazard ratio, 0.68; P = .0022). Median PFS was 6.2 months versus 5.6 months (HR, 0.59; P < .0001).

The confirmed overall response rate was 37% for the cemiplimab arm versus 21% for the chemotherapy arm.

The most common adverse reactions (>10%) with cemiplimab-rlwc were musculoskeletal pain, rash, anemia, fatigue, decreased appetite, pneumonia, and cough.

This approval “means physicians and patients have a potent new treatment option against this deadly disease,” said Naiyer Rizvi, MD, Price Family Professor of Medicine, director of thoracic oncology, and codirector of cancer immunotherapy at Columbia University Irving Medical Center, New York, in a statement. He was a steering committee member on the EMPOWER-Lung-1 Trial.

“Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases or who had locally advanced disease and were not candidates for definitive chemoradiation,” said Dr. Rizvi. “This gives doctors important new data when considering Libtayo for the varied patients and situations they treat in daily clinical practice.”

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

The Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) for the treatment of advanced non–small cell lung cancer (NSCLC).

Specifically, the indication is for first-line treatment as monotherapy for patients with locally advanced or metastatic disease who are not candidates for surgical resection or definitive chemoradiotherapy and whose tumors have a high expression of programmed death–ligand 1 (PD-L1) (Tumor Proportion Score >50%), as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations.

This is the third indication for cemiplimab-rlwc, a monoclonal antibody and PD-1 inhibitor.

In February, it was approved as the first immunotherapy to treat patients with locally advanced or metastatic basal cell carcinoma that was previously treated with a hedgehog pathway inhibitor or for whom a hedgehog inhibitor is inappropriate.

Cemiplimab-rlwc previously received FDA approval in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma for patients who were not eligible for curative surgery or radiotherapy. At the time, Karl Lewis, MD, a professor at the University of Colorado at Denver, Aurora, and a trial investigator, predicted that the drug “will change the treatment paradigm for patients with advanced basal cell carcinoma.”
 

Outperforms chemotherapy

The approval for use in NSCLC is based on results from the phase 3, open-label EMPOWER-Lung 1 trial, which randomly assigned 710 patients in a 1:1 ratio to receive either cemiplimab-rwlc or platinum-doublet chemotherapy. Patients had either locally advanced NSCLC and were not candidates for surgical resection or definitive chemoradiotherapy, or they had metastatic NSCLC.

Patients in the experimental arm received cemiplimab-rwlc 350 mg intravenously every 3 weeks. The primary efficacy outcome measures were overall survival (OS) and progression-free survival (PFS), determined on the basis of blinded independent central review.

Results showed statistically significant improvements in both outcomes. Median OS was 22.1 months with cemiplimab-rwlc versus 14.3 months with chemotherapy (hazard ratio, 0.68; P = .0022). Median PFS was 6.2 months versus 5.6 months (HR, 0.59; P < .0001).

The confirmed overall response rate was 37% for the cemiplimab arm versus 21% for the chemotherapy arm.

The most common adverse reactions (>10%) with cemiplimab-rlwc were musculoskeletal pain, rash, anemia, fatigue, decreased appetite, pneumonia, and cough.

This approval “means physicians and patients have a potent new treatment option against this deadly disease,” said Naiyer Rizvi, MD, Price Family Professor of Medicine, director of thoracic oncology, and codirector of cancer immunotherapy at Columbia University Irving Medical Center, New York, in a statement. He was a steering committee member on the EMPOWER-Lung-1 Trial.

“Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases or who had locally advanced disease and were not candidates for definitive chemoradiation,” said Dr. Rizvi. “This gives doctors important new data when considering Libtayo for the varied patients and situations they treat in daily clinical practice.”

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

The Food and Drug Administration has approved cemiplimab-rwlc (Libtayo) for the treatment of advanced non–small cell lung cancer (NSCLC).

Specifically, the indication is for first-line treatment as monotherapy for patients with locally advanced or metastatic disease who are not candidates for surgical resection or definitive chemoradiotherapy and whose tumors have a high expression of programmed death–ligand 1 (PD-L1) (Tumor Proportion Score >50%), as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations.

This is the third indication for cemiplimab-rlwc, a monoclonal antibody and PD-1 inhibitor.

In February, it was approved as the first immunotherapy to treat patients with locally advanced or metastatic basal cell carcinoma that was previously treated with a hedgehog pathway inhibitor or for whom a hedgehog inhibitor is inappropriate.

Cemiplimab-rlwc previously received FDA approval in 2018 for locally advanced or metastatic cutaneous squamous cell carcinoma for patients who were not eligible for curative surgery or radiotherapy. At the time, Karl Lewis, MD, a professor at the University of Colorado at Denver, Aurora, and a trial investigator, predicted that the drug “will change the treatment paradigm for patients with advanced basal cell carcinoma.”
 

Outperforms chemotherapy

The approval for use in NSCLC is based on results from the phase 3, open-label EMPOWER-Lung 1 trial, which randomly assigned 710 patients in a 1:1 ratio to receive either cemiplimab-rwlc or platinum-doublet chemotherapy. Patients had either locally advanced NSCLC and were not candidates for surgical resection or definitive chemoradiotherapy, or they had metastatic NSCLC.

Patients in the experimental arm received cemiplimab-rwlc 350 mg intravenously every 3 weeks. The primary efficacy outcome measures were overall survival (OS) and progression-free survival (PFS), determined on the basis of blinded independent central review.

Results showed statistically significant improvements in both outcomes. Median OS was 22.1 months with cemiplimab-rwlc versus 14.3 months with chemotherapy (hazard ratio, 0.68; P = .0022). Median PFS was 6.2 months versus 5.6 months (HR, 0.59; P < .0001).

The confirmed overall response rate was 37% for the cemiplimab arm versus 21% for the chemotherapy arm.

The most common adverse reactions (>10%) with cemiplimab-rlwc were musculoskeletal pain, rash, anemia, fatigue, decreased appetite, pneumonia, and cough.

This approval “means physicians and patients have a potent new treatment option against this deadly disease,” said Naiyer Rizvi, MD, Price Family Professor of Medicine, director of thoracic oncology, and codirector of cancer immunotherapy at Columbia University Irving Medical Center, New York, in a statement. He was a steering committee member on the EMPOWER-Lung-1 Trial.

“Notably, Libtayo was approved based on a pivotal trial where most chemotherapy patients crossed over to Libtayo following disease progression, and that allowed for frequently underrepresented patients who had pretreated and clinically stable brain metastases or who had locally advanced disease and were not candidates for definitive chemoradiation,” said Dr. Rizvi. “This gives doctors important new data when considering Libtayo for the varied patients and situations they treat in daily clinical practice.”

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

Endometriosis, which affects 1 in 10 women, is one of the most common conditions that gynecologists treat. It is known to cause pain, pelvic adhesive disease, endometriotic cyst formation, and infertility. However, even more sinister, it also increases a woman’s risk for the development of epithelial ovarian cancer (known as endometriosis-associated ovarian cancer or EAOC). A woman with endometriosis has a two- to threefold increased risk of developing epithelial ovarian cancer, compared with nonaffected women.¹ This risk appears to be concentrated in the premenopausal age group, particularly the fifth decade of life. After menopause their risk of developing cancer returns to a baseline level.

EAOC classically presents as clear cell or endometrioid adenocarcinomas, rather than high-grade serous carcinomas. However, low-grade serous carcinomas are also frequently observed in this cohort.^2,3 Unlike high-grade serous carcinoma, EAOC is more likely to be diagnosed at an early stage, with the majority at stage I or II, and prognosis is better. After matching for age and stage with cases of high-grade serous carcinoma, there is improved disease-free and overall survival observed among cases of EAOC of clear cell and endometrioid histologic cell types.⁴ The phenomenon of dual primaries (synchronous endometrial and ovarian cancer) occurs more frequently in EAOC than it does in patients with nonendometriosis-related high-grade serous cancer (25% vs. 4%).

The genomics of these endometriosis-associated cancers are quite distinct. Similar to benign endometriosis implants, EAOC is associated with genomic mutations in ARID1A, PIK3CA, and PTEN, as well as progesterone resistance.^1,2 Multiple studies have shown that the adjacent eutopic endometrium carries similar gene mutations as those found in both benign endometriotic implants and EAOC.² This may explain the higher incidence (twofold) of endometrial cancer in patients with endometriosis as well as the increased incidence of dual ovarian and endometrial cancer primaries.

Just as there are multiple theories regarding the mechanism of benign endometriosis, we have theories rather than conclusions regarding the origins of EAOC. One such theory is that it develops from malignant transformation in an existing endometriotic cyst.⁵ Endometriotic cysts provide an iron-rich environment which promotes reactive oxygen species that promote carcinogenesis by inducing gene mutations and epigenetic alterations. However, if prolonged exposure to oxidative stress within endometriotic cysts were to be the cause for EAOC, we would expect to see a progressively increasing incidence of ovarian cancer over time in patients with expectantly managed cysts. However, in cases of expectant management, an initial, early, increased risk for cancer within the first 5 years is followed by a subsequent decreasing incidence over time.⁶ This early incidence spike suggests that some endometriotic cysts may have been misclassified as benign, then rapidly declare themselves as malignant during the observation period rather than a transformation into malignancy from a benign endometrioma over time.

An alternative, and favored, theory for the origins of EAOC are that endometrial cells with carcinogenic genomic alterations reflux through the fallopian tubes during menstruation and settle onto the ovarian epithelium which itself is damaged from recent ovulation thus providing an environment that is highly suitable for oncogenesis.² Genomic analyses of both the eutopic endometrium and malignant cells in patients with EAOC have shown that both tissues contain the same genomic alterations.¹ Given that menstruation, including retrograde menstruation, ends after menopause, this mechanism supports the observation that EAOC is predominantly a malignancy of premenopausal women. Additionally, salpingectomy and hysterectomy confers a protective effect on the development of EAOC, theoretically by preventing the retrograde transfer of these mutant progenitor endometrial cells. Furthermore, the factors that increase the number of menstrual cycles (such as an early age of menarche and delayed or nonchildbearing states) increases the risk for EAOC and factors that inhibit menstruation, such as oral contraceptive pill use, appear to decrease its risk.

EAOC most commonly arises in the ovary, and not in the deep endometriosis implants of adjacent pelvic structures (such as the anterior and posterior cul de sac and pelvic peritoneum). It is suggested that the ovary itself provides a uniquely favorable environment for carcinogenesis. As stated above, it is hypothesized that refluxed endometrial cells, carrying important progenitor mutations, may become trapped in the tissues of traumatized ovarian epithelium, ripe with inflammatory changes, post ovulation.² This microenvironment may promote the development of malignancy.

Given these theories and their supporting evidence, how can we attempt to reduce the incidence of this cancer for our patients with endometriosis? Despite their increased risk for ovarian and endometrial cancers, current recommendations do not support routine cancer screening in women with endometriosis.⁷ However, risk-mitigation strategies can still be pursued. Hormonal contraceptives to decrease ovulation and menstrual cycling are protective against ovarian cancer and are also helpful in mitigating the symptoms of endometriosis. While removal of endometriotic cysts may not, in and of itself, be a strategy to prevent EAOC, it is still generally recommended because these cysts are commonly a source of pain and infertility. While they do not appear to undergo malignant transformation, it can be difficult to definitively rule out an early ovarian cancer in these complex ovarian cysts, particularly as they are often associated with tumor marker abnormalities such as elevations in CA 125. Therefore, if surgical excision of an endometriotic cyst is not performed, it should be closely followed for at least 5 years to ensure it is a benign structure. If surgery is pursued and ovarian preservation is desired, removal of the fallopian tubes and uterus can help mitigate the risk for EAOC.⁸

Endometriosis is a morbid condition for many young women. In addition to causing pain and infertility it increases a woman’s risk for ovarian and endometrial cancer, particularly ovarian clear cell, endometrioid, and low-grade serous cancers and synchronous endometrial and ovarian cancers. Endometriotic cysts should be removed or closely monitored, and clinicians should discuss treatment options that minimize frequency of ovulation and menstruation events as a preventative strategy.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Endocrinology. 2019;160(3):626-38.

2. Cancers. 2020;12(6):1676.

3. Lancet Oncol. 2012;13:385-94.

4. Gynecol Oncol. 2014;132(3):760-6.

5. Redox Rep. 2016;21:119-26.

6. Int. J Clin Oncol. 2020;25:51-8.

7. Hum Reprod. 2013;28:1552-68.

8. J Natl Cancer Inst. 2019;111:1097-103.

Endometriosis, which affects 1 in 10 women, is one of the most common conditions that gynecologists treat. It is known to cause pain, pelvic adhesive disease, endometriotic cyst formation, and infertility. However, even more sinister, it also increases a woman’s risk for the development of epithelial ovarian cancer (known as endometriosis-associated ovarian cancer or EAOC). A woman with endometriosis has a two- to threefold increased risk of developing epithelial ovarian cancer, compared with nonaffected women.¹ This risk appears to be concentrated in the premenopausal age group, particularly the fifth decade of life. After menopause their risk of developing cancer returns to a baseline level.

EAOC classically presents as clear cell or endometrioid adenocarcinomas, rather than high-grade serous carcinomas. However, low-grade serous carcinomas are also frequently observed in this cohort.^2,3 Unlike high-grade serous carcinoma, EAOC is more likely to be diagnosed at an early stage, with the majority at stage I or II, and prognosis is better. After matching for age and stage with cases of high-grade serous carcinoma, there is improved disease-free and overall survival observed among cases of EAOC of clear cell and endometrioid histologic cell types.⁴ The phenomenon of dual primaries (synchronous endometrial and ovarian cancer) occurs more frequently in EAOC than it does in patients with nonendometriosis-related high-grade serous cancer (25% vs. 4%).

The genomics of these endometriosis-associated cancers are quite distinct. Similar to benign endometriosis implants, EAOC is associated with genomic mutations in ARID1A, PIK3CA, and PTEN, as well as progesterone resistance.^1,2 Multiple studies have shown that the adjacent eutopic endometrium carries similar gene mutations as those found in both benign endometriotic implants and EAOC.² This may explain the higher incidence (twofold) of endometrial cancer in patients with endometriosis as well as the increased incidence of dual ovarian and endometrial cancer primaries.

Just as there are multiple theories regarding the mechanism of benign endometriosis, we have theories rather than conclusions regarding the origins of EAOC. One such theory is that it develops from malignant transformation in an existing endometriotic cyst.⁵ Endometriotic cysts provide an iron-rich environment which promotes reactive oxygen species that promote carcinogenesis by inducing gene mutations and epigenetic alterations. However, if prolonged exposure to oxidative stress within endometriotic cysts were to be the cause for EAOC, we would expect to see a progressively increasing incidence of ovarian cancer over time in patients with expectantly managed cysts. However, in cases of expectant management, an initial, early, increased risk for cancer within the first 5 years is followed by a subsequent decreasing incidence over time.⁶ This early incidence spike suggests that some endometriotic cysts may have been misclassified as benign, then rapidly declare themselves as malignant during the observation period rather than a transformation into malignancy from a benign endometrioma over time.

An alternative, and favored, theory for the origins of EAOC are that endometrial cells with carcinogenic genomic alterations reflux through the fallopian tubes during menstruation and settle onto the ovarian epithelium which itself is damaged from recent ovulation thus providing an environment that is highly suitable for oncogenesis.² Genomic analyses of both the eutopic endometrium and malignant cells in patients with EAOC have shown that both tissues contain the same genomic alterations.¹ Given that menstruation, including retrograde menstruation, ends after menopause, this mechanism supports the observation that EAOC is predominantly a malignancy of premenopausal women. Additionally, salpingectomy and hysterectomy confers a protective effect on the development of EAOC, theoretically by preventing the retrograde transfer of these mutant progenitor endometrial cells. Furthermore, the factors that increase the number of menstrual cycles (such as an early age of menarche and delayed or nonchildbearing states) increases the risk for EAOC and factors that inhibit menstruation, such as oral contraceptive pill use, appear to decrease its risk.

EAOC most commonly arises in the ovary, and not in the deep endometriosis implants of adjacent pelvic structures (such as the anterior and posterior cul de sac and pelvic peritoneum). It is suggested that the ovary itself provides a uniquely favorable environment for carcinogenesis. As stated above, it is hypothesized that refluxed endometrial cells, carrying important progenitor mutations, may become trapped in the tissues of traumatized ovarian epithelium, ripe with inflammatory changes, post ovulation.² This microenvironment may promote the development of malignancy.

Given these theories and their supporting evidence, how can we attempt to reduce the incidence of this cancer for our patients with endometriosis? Despite their increased risk for ovarian and endometrial cancers, current recommendations do not support routine cancer screening in women with endometriosis.⁷ However, risk-mitigation strategies can still be pursued. Hormonal contraceptives to decrease ovulation and menstrual cycling are protective against ovarian cancer and are also helpful in mitigating the symptoms of endometriosis. While removal of endometriotic cysts may not, in and of itself, be a strategy to prevent EAOC, it is still generally recommended because these cysts are commonly a source of pain and infertility. While they do not appear to undergo malignant transformation, it can be difficult to definitively rule out an early ovarian cancer in these complex ovarian cysts, particularly as they are often associated with tumor marker abnormalities such as elevations in CA 125. Therefore, if surgical excision of an endometriotic cyst is not performed, it should be closely followed for at least 5 years to ensure it is a benign structure. If surgery is pursued and ovarian preservation is desired, removal of the fallopian tubes and uterus can help mitigate the risk for EAOC.⁸

Endometriosis is a morbid condition for many young women. In addition to causing pain and infertility it increases a woman’s risk for ovarian and endometrial cancer, particularly ovarian clear cell, endometrioid, and low-grade serous cancers and synchronous endometrial and ovarian cancers. Endometriotic cysts should be removed or closely monitored, and clinicians should discuss treatment options that minimize frequency of ovulation and menstruation events as a preventative strategy.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Endocrinology. 2019;160(3):626-38.

2. Cancers. 2020;12(6):1676.

3. Lancet Oncol. 2012;13:385-94.

4. Gynecol Oncol. 2014;132(3):760-6.

5. Redox Rep. 2016;21:119-26.

6. Int. J Clin Oncol. 2020;25:51-8.

7. Hum Reprod. 2013;28:1552-68.

8. J Natl Cancer Inst. 2019;111:1097-103.

Endometriosis, which affects 1 in 10 women, is one of the most common conditions that gynecologists treat. It is known to cause pain, pelvic adhesive disease, endometriotic cyst formation, and infertility. However, even more sinister, it also increases a woman’s risk for the development of epithelial ovarian cancer (known as endometriosis-associated ovarian cancer or EAOC). A woman with endometriosis has a two- to threefold increased risk of developing epithelial ovarian cancer, compared with nonaffected women.¹ This risk appears to be concentrated in the premenopausal age group, particularly the fifth decade of life. After menopause their risk of developing cancer returns to a baseline level.

EAOC classically presents as clear cell or endometrioid adenocarcinomas, rather than high-grade serous carcinomas. However, low-grade serous carcinomas are also frequently observed in this cohort.^2,3 Unlike high-grade serous carcinoma, EAOC is more likely to be diagnosed at an early stage, with the majority at stage I or II, and prognosis is better. After matching for age and stage with cases of high-grade serous carcinoma, there is improved disease-free and overall survival observed among cases of EAOC of clear cell and endometrioid histologic cell types.⁴ The phenomenon of dual primaries (synchronous endometrial and ovarian cancer) occurs more frequently in EAOC than it does in patients with nonendometriosis-related high-grade serous cancer (25% vs. 4%).

The genomics of these endometriosis-associated cancers are quite distinct. Similar to benign endometriosis implants, EAOC is associated with genomic mutations in ARID1A, PIK3CA, and PTEN, as well as progesterone resistance.^1,2 Multiple studies have shown that the adjacent eutopic endometrium carries similar gene mutations as those found in both benign endometriotic implants and EAOC.² This may explain the higher incidence (twofold) of endometrial cancer in patients with endometriosis as well as the increased incidence of dual ovarian and endometrial cancer primaries.

Just as there are multiple theories regarding the mechanism of benign endometriosis, we have theories rather than conclusions regarding the origins of EAOC. One such theory is that it develops from malignant transformation in an existing endometriotic cyst.⁵ Endometriotic cysts provide an iron-rich environment which promotes reactive oxygen species that promote carcinogenesis by inducing gene mutations and epigenetic alterations. However, if prolonged exposure to oxidative stress within endometriotic cysts were to be the cause for EAOC, we would expect to see a progressively increasing incidence of ovarian cancer over time in patients with expectantly managed cysts. However, in cases of expectant management, an initial, early, increased risk for cancer within the first 5 years is followed by a subsequent decreasing incidence over time.⁶ This early incidence spike suggests that some endometriotic cysts may have been misclassified as benign, then rapidly declare themselves as malignant during the observation period rather than a transformation into malignancy from a benign endometrioma over time.

An alternative, and favored, theory for the origins of EAOC are that endometrial cells with carcinogenic genomic alterations reflux through the fallopian tubes during menstruation and settle onto the ovarian epithelium which itself is damaged from recent ovulation thus providing an environment that is highly suitable for oncogenesis.² Genomic analyses of both the eutopic endometrium and malignant cells in patients with EAOC have shown that both tissues contain the same genomic alterations.¹ Given that menstruation, including retrograde menstruation, ends after menopause, this mechanism supports the observation that EAOC is predominantly a malignancy of premenopausal women. Additionally, salpingectomy and hysterectomy confers a protective effect on the development of EAOC, theoretically by preventing the retrograde transfer of these mutant progenitor endometrial cells. Furthermore, the factors that increase the number of menstrual cycles (such as an early age of menarche and delayed or nonchildbearing states) increases the risk for EAOC and factors that inhibit menstruation, such as oral contraceptive pill use, appear to decrease its risk.

EAOC most commonly arises in the ovary, and not in the deep endometriosis implants of adjacent pelvic structures (such as the anterior and posterior cul de sac and pelvic peritoneum). It is suggested that the ovary itself provides a uniquely favorable environment for carcinogenesis. As stated above, it is hypothesized that refluxed endometrial cells, carrying important progenitor mutations, may become trapped in the tissues of traumatized ovarian epithelium, ripe with inflammatory changes, post ovulation.² This microenvironment may promote the development of malignancy.

Given these theories and their supporting evidence, how can we attempt to reduce the incidence of this cancer for our patients with endometriosis? Despite their increased risk for ovarian and endometrial cancers, current recommendations do not support routine cancer screening in women with endometriosis.⁷ However, risk-mitigation strategies can still be pursued. Hormonal contraceptives to decrease ovulation and menstrual cycling are protective against ovarian cancer and are also helpful in mitigating the symptoms of endometriosis. While removal of endometriotic cysts may not, in and of itself, be a strategy to prevent EAOC, it is still generally recommended because these cysts are commonly a source of pain and infertility. While they do not appear to undergo malignant transformation, it can be difficult to definitively rule out an early ovarian cancer in these complex ovarian cysts, particularly as they are often associated with tumor marker abnormalities such as elevations in CA 125. Therefore, if surgical excision of an endometriotic cyst is not performed, it should be closely followed for at least 5 years to ensure it is a benign structure. If surgery is pursued and ovarian preservation is desired, removal of the fallopian tubes and uterus can help mitigate the risk for EAOC.⁸

Endometriosis is a morbid condition for many young women. In addition to causing pain and infertility it increases a woman’s risk for ovarian and endometrial cancer, particularly ovarian clear cell, endometrioid, and low-grade serous cancers and synchronous endometrial and ovarian cancers. Endometriotic cysts should be removed or closely monitored, and clinicians should discuss treatment options that minimize frequency of ovulation and menstruation events as a preventative strategy.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Endocrinology. 2019;160(3):626-38.

2. Cancers. 2020;12(6):1676.

3. Lancet Oncol. 2012;13:385-94.

4. Gynecol Oncol. 2014;132(3):760-6.

5. Redox Rep. 2016;21:119-26.

6. Int. J Clin Oncol. 2020;25:51-8.

7. Hum Reprod. 2013;28:1552-68.

8. J Natl Cancer Inst. 2019;111:1097-103.

An integrated analysis of data derived from 99 treatment-naive glioblastomas has identified characteristics that could help stratify patients for more effective treatment, according to the investigators.

The analysis provides a detailed map of genes, proteins, infiltrating cells, and signaling pathways that play key roles in driving glioblastoma, Liang-Bo Wang, MD, of Washington University in St. Louis, and colleagues reported in Cancer Cell.

For example, the team identified key phosphorylation events as potential mediators of oncogenic pathway activation and potential targets for EGFR-, TP53-, and RB1-altered tumors. Specifically, phosphorylated PTPN11 and PLCG1 represent a signaling hub in RTK-altered tumors, they found.

The investigators also identified four immune glioblastoma tumor subtypes characterized by distinct immune cell populations. Type 1 tumors have a high macrophage count and few T cells, type 2 tumors have a moderate macrophage count, type 3 tumors have a high T-cell count and few macrophages, and type 4 tumors have few or no immune cells of any type.

They also found that mesenchymal subtype EMT signature is specific to tumor cells but not to stroma, and histone H2B acetylation is enriched in classical glioblastomas with low macrophage content.

“To improve therapies for this deadly cancer, understanding the tumor cells themselves is important but not enough,” senior author Li Ding, PhD, a professor of medicine and genetics and director of computational biology in the division of oncology at Washington University stated in a press release. “We also must understand the tumor cells’ interactions with the surrounding environment, including immune cells and the connective tissues and blood vessels.”

The investigators, including researchers from Pacific Northwest National Laboratory, Case Western Reserve University, and the National Cancer Institute, performed high-resolution and high-depth analyses on 99 tumors.

“Harnessing new technologies, including proteomics, metabolomics, and single-cell sequencing, this study is an extremely deep dive into glioblastoma tumor biology, revealing new possibilities for therapy,” Dr. Ding said.

The study, which is part of the NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), is the largest and most detailed schematic of glioblastoma tumors to date, according to the press release.

The most immediate implication of the findings is better clinical trial design, study coauthor Milan G. Chheda, MD, stated in the press release.

Stratifying patients by tumor type, as identified in the current analysis, could allow researchers to test targeted therapies in the tumors most likely to respond to those therapies, explained Dr. Chheda, of Siteman Cancer Center at Barnes Jewish Hospital and Washington University.

The findings, particularly of multiple glioblastoma tumor subtypes, may explain the negative findings of trials looking at various immunotherapies for treating glioblastoma. Investigators for those trials haven’t considered the possibility of immune subgroups that may respond differently, the authors note, adding that research is underway to identify the best drugs to assess for the newly identified glioblastoma tumor types.

The study was supported by grants from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium, the National Human Genome Research Institute, and the National Institutes of Health.

Dr. Wang and Dr. Ding reported having no disclosures. Dr. Chheda receives research support from NeoimmuneTech and Orbus Therapeutics, and royalties from UpToDate.

sworcester@mdedge.com

An integrated analysis of data derived from 99 treatment-naive glioblastomas has identified characteristics that could help stratify patients for more effective treatment, according to the investigators.

The analysis provides a detailed map of genes, proteins, infiltrating cells, and signaling pathways that play key roles in driving glioblastoma, Liang-Bo Wang, MD, of Washington University in St. Louis, and colleagues reported in Cancer Cell.

For example, the team identified key phosphorylation events as potential mediators of oncogenic pathway activation and potential targets for EGFR-, TP53-, and RB1-altered tumors. Specifically, phosphorylated PTPN11 and PLCG1 represent a signaling hub in RTK-altered tumors, they found.

The investigators also identified four immune glioblastoma tumor subtypes characterized by distinct immune cell populations. Type 1 tumors have a high macrophage count and few T cells, type 2 tumors have a moderate macrophage count, type 3 tumors have a high T-cell count and few macrophages, and type 4 tumors have few or no immune cells of any type.

They also found that mesenchymal subtype EMT signature is specific to tumor cells but not to stroma, and histone H2B acetylation is enriched in classical glioblastomas with low macrophage content.

“To improve therapies for this deadly cancer, understanding the tumor cells themselves is important but not enough,” senior author Li Ding, PhD, a professor of medicine and genetics and director of computational biology in the division of oncology at Washington University stated in a press release. “We also must understand the tumor cells’ interactions with the surrounding environment, including immune cells and the connective tissues and blood vessels.”

The investigators, including researchers from Pacific Northwest National Laboratory, Case Western Reserve University, and the National Cancer Institute, performed high-resolution and high-depth analyses on 99 tumors.

“Harnessing new technologies, including proteomics, metabolomics, and single-cell sequencing, this study is an extremely deep dive into glioblastoma tumor biology, revealing new possibilities for therapy,” Dr. Ding said.

The study, which is part of the NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), is the largest and most detailed schematic of glioblastoma tumors to date, according to the press release.

The most immediate implication of the findings is better clinical trial design, study coauthor Milan G. Chheda, MD, stated in the press release.

Stratifying patients by tumor type, as identified in the current analysis, could allow researchers to test targeted therapies in the tumors most likely to respond to those therapies, explained Dr. Chheda, of Siteman Cancer Center at Barnes Jewish Hospital and Washington University.

The findings, particularly of multiple glioblastoma tumor subtypes, may explain the negative findings of trials looking at various immunotherapies for treating glioblastoma. Investigators for those trials haven’t considered the possibility of immune subgroups that may respond differently, the authors note, adding that research is underway to identify the best drugs to assess for the newly identified glioblastoma tumor types.

The study was supported by grants from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium, the National Human Genome Research Institute, and the National Institutes of Health.

Dr. Wang and Dr. Ding reported having no disclosures. Dr. Chheda receives research support from NeoimmuneTech and Orbus Therapeutics, and royalties from UpToDate.

sworcester@mdedge.com

An integrated analysis of data derived from 99 treatment-naive glioblastomas has identified characteristics that could help stratify patients for more effective treatment, according to the investigators.

The analysis provides a detailed map of genes, proteins, infiltrating cells, and signaling pathways that play key roles in driving glioblastoma, Liang-Bo Wang, MD, of Washington University in St. Louis, and colleagues reported in Cancer Cell.

For example, the team identified key phosphorylation events as potential mediators of oncogenic pathway activation and potential targets for EGFR-, TP53-, and RB1-altered tumors. Specifically, phosphorylated PTPN11 and PLCG1 represent a signaling hub in RTK-altered tumors, they found.

The investigators also identified four immune glioblastoma tumor subtypes characterized by distinct immune cell populations. Type 1 tumors have a high macrophage count and few T cells, type 2 tumors have a moderate macrophage count, type 3 tumors have a high T-cell count and few macrophages, and type 4 tumors have few or no immune cells of any type.

They also found that mesenchymal subtype EMT signature is specific to tumor cells but not to stroma, and histone H2B acetylation is enriched in classical glioblastomas with low macrophage content.

“To improve therapies for this deadly cancer, understanding the tumor cells themselves is important but not enough,” senior author Li Ding, PhD, a professor of medicine and genetics and director of computational biology in the division of oncology at Washington University stated in a press release. “We also must understand the tumor cells’ interactions with the surrounding environment, including immune cells and the connective tissues and blood vessels.”

The investigators, including researchers from Pacific Northwest National Laboratory, Case Western Reserve University, and the National Cancer Institute, performed high-resolution and high-depth analyses on 99 tumors.

“Harnessing new technologies, including proteomics, metabolomics, and single-cell sequencing, this study is an extremely deep dive into glioblastoma tumor biology, revealing new possibilities for therapy,” Dr. Ding said.

The study, which is part of the NCI’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), is the largest and most detailed schematic of glioblastoma tumors to date, according to the press release.

The most immediate implication of the findings is better clinical trial design, study coauthor Milan G. Chheda, MD, stated in the press release.

Stratifying patients by tumor type, as identified in the current analysis, could allow researchers to test targeted therapies in the tumors most likely to respond to those therapies, explained Dr. Chheda, of Siteman Cancer Center at Barnes Jewish Hospital and Washington University.

The findings, particularly of multiple glioblastoma tumor subtypes, may explain the negative findings of trials looking at various immunotherapies for treating glioblastoma. Investigators for those trials haven’t considered the possibility of immune subgroups that may respond differently, the authors note, adding that research is underway to identify the best drugs to assess for the newly identified glioblastoma tumor types.

The study was supported by grants from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium, the National Human Genome Research Institute, and the National Institutes of Health.

Dr. Wang and Dr. Ding reported having no disclosures. Dr. Chheda receives research support from NeoimmuneTech and Orbus Therapeutics, and royalties from UpToDate.

sworcester@mdedge.com

There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.

The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.

“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).

Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.

Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.

Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.

The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.

Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).

There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.

The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.

“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.

“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.

“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”

Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.

Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.

Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.

COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.

Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.

The funding source wasn’t reported. The speakers had no relevant disclosures.

aotto@mdedge.com

There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.

The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.

“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).

Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.

Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.

Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.

The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.

Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).

There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.

The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.

“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.

“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.

“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”

Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.

Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.

Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.

COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.

Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.

The funding source wasn’t reported. The speakers had no relevant disclosures.

aotto@mdedge.com

There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.

The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.

“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).

Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.

Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.

Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.

The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.

Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).

There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.

The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.

“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.

“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.

“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”

Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.

Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.

Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.

COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.

Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.

The funding source wasn’t reported. The speakers had no relevant disclosures.

aotto@mdedge.com