Jim Kling

Among patients with stage II or stage III rectal adenocarcinoma, organ preservation is achievable in up to half of patients who undergo total neoadjuvant chemotherapy (TNT), according to the results from a new randomized phase 2 trial.

The study included 324 patients from 18 centers who were randomized into one of two groups: induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT). Patients in both groups then underwent either total mesorectal excision (TME) or a watch-and-wait strategy, depending on tumor response.

“What the study shows is that the order of the chemo and the radiation dose doesn’t affect survival, but it seems to affect the probability of preserving the rectum. That data is consistent with other studies that have compared head-to-head chemotherapy followed by radiation versus radiation followed by chemotherapy. In addition, the survival rate for this study is no different from other prospective studies that included patients with similar-stage tumors selected by MRI. So the data suggest that you can probably avoid surgery in half of the patients with locally advanced rectal cancer and still achieve similar survival compared to patients treated with more conventional neoadjuvant treatments and mandatory surgery,” said lead author Julio Garcia-Aguilar, MD, PhD, in an interview.

“It is a significant shift in the treatment paradigm, that can potentially benefit half of the 50,000 rectal cancer patients diagnosed every year in the United States,” said Dr. Garcia-Aguilar, chief of colorectal surgery at Memorial Sloan Kettering Cancer Center, New York.

The study was published online in the Journal of Clinical Oncology.

Neoadjuvant CRT, TME, and adjuvant chemotherapy is an effective treatment strategy for locally advanced rectal adenocarcinoma, but the regimen can cause bowel, urinary, and sexual dysfunction. The majority of adverse effects from the therapy can be traced to surgery. In addition, some patients with distal rectal cancer often require a permanent colostomy.

TNT is a newer approach that delivers chemotherapy plus radiotherapy before surgery. It is designed to improve treatment compliance and eradicate micrometastases in advance of surgery.

After a median follow-up of 3 years, disease-free survival (76% in both groups) was similar to historical controls (75%). Both groups had similar rates of local recurrence-free survival (94% each) and distant metastasis–free survival (84% for INCT-CRT and 82% for CRT-CNCT).

Following TNT, 26% of patients were recommended for TME, including 28% in the INCT-CRT group and 24% in the CRT-CNCT group, and the rest offered watchful-waiting. Forty percent of those in the INCT-CRT group and 27% in the CRT-CNCT group who went on to watchful waiting had tumor regrowth. Of these combined 75 patients, 67 underwent successful salvage surgery.

In the intention-to-treat analysis, 53% of patients had a preserved rectum at 3 years (95% confidence interval, 45%-62%) in the CRT-CNCT group versus 41% in the INCT-CRT group (95% CI, 33%-50%; P = .01).

The new results reinforce other results and should contribute to shifting clinical practice, according to Dr. Garcia-Aguilar. “I think what we have learned is that rectal cancers respond to chemotherapy and radiation at a higher rate that we thought previously, but that the response takes time. That’s something that we use currently in an adaptive way to modify the treatment as we observe the tumor response,” he said.

The slow regrowth means that patients can be closely monitored without undue risk, but such an approach demands buy-in from the patient. “The patient needs to be compliant with a close surveillance protocol, because otherwise it can be a disaster. I think that’s really part of the message,” Dr. Garcia-Aguilar said.

Dr. Garcia-Aguilar has an ownership interest in Intuitive Surgical and has advised or consulted for Medtronic, Intuitive Surgical, and Johnson & Johnson.

Among patients with stage II or stage III rectal adenocarcinoma, organ preservation is achievable in up to half of patients who undergo total neoadjuvant chemotherapy (TNT), according to the results from a new randomized phase 2 trial.

The study included 324 patients from 18 centers who were randomized into one of two groups: induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT). Patients in both groups then underwent either total mesorectal excision (TME) or a watch-and-wait strategy, depending on tumor response.

“What the study shows is that the order of the chemo and the radiation dose doesn’t affect survival, but it seems to affect the probability of preserving the rectum. That data is consistent with other studies that have compared head-to-head chemotherapy followed by radiation versus radiation followed by chemotherapy. In addition, the survival rate for this study is no different from other prospective studies that included patients with similar-stage tumors selected by MRI. So the data suggest that you can probably avoid surgery in half of the patients with locally advanced rectal cancer and still achieve similar survival compared to patients treated with more conventional neoadjuvant treatments and mandatory surgery,” said lead author Julio Garcia-Aguilar, MD, PhD, in an interview.

“It is a significant shift in the treatment paradigm, that can potentially benefit half of the 50,000 rectal cancer patients diagnosed every year in the United States,” said Dr. Garcia-Aguilar, chief of colorectal surgery at Memorial Sloan Kettering Cancer Center, New York.

The study was published online in the Journal of Clinical Oncology.

Neoadjuvant CRT, TME, and adjuvant chemotherapy is an effective treatment strategy for locally advanced rectal adenocarcinoma, but the regimen can cause bowel, urinary, and sexual dysfunction. The majority of adverse effects from the therapy can be traced to surgery. In addition, some patients with distal rectal cancer often require a permanent colostomy.

TNT is a newer approach that delivers chemotherapy plus radiotherapy before surgery. It is designed to improve treatment compliance and eradicate micrometastases in advance of surgery.

After a median follow-up of 3 years, disease-free survival (76% in both groups) was similar to historical controls (75%). Both groups had similar rates of local recurrence-free survival (94% each) and distant metastasis–free survival (84% for INCT-CRT and 82% for CRT-CNCT).

Following TNT, 26% of patients were recommended for TME, including 28% in the INCT-CRT group and 24% in the CRT-CNCT group, and the rest offered watchful-waiting. Forty percent of those in the INCT-CRT group and 27% in the CRT-CNCT group who went on to watchful waiting had tumor regrowth. Of these combined 75 patients, 67 underwent successful salvage surgery.

In the intention-to-treat analysis, 53% of patients had a preserved rectum at 3 years (95% confidence interval, 45%-62%) in the CRT-CNCT group versus 41% in the INCT-CRT group (95% CI, 33%-50%; P = .01).

The new results reinforce other results and should contribute to shifting clinical practice, according to Dr. Garcia-Aguilar. “I think what we have learned is that rectal cancers respond to chemotherapy and radiation at a higher rate that we thought previously, but that the response takes time. That’s something that we use currently in an adaptive way to modify the treatment as we observe the tumor response,” he said.

The slow regrowth means that patients can be closely monitored without undue risk, but such an approach demands buy-in from the patient. “The patient needs to be compliant with a close surveillance protocol, because otherwise it can be a disaster. I think that’s really part of the message,” Dr. Garcia-Aguilar said.

Dr. Garcia-Aguilar has an ownership interest in Intuitive Surgical and has advised or consulted for Medtronic, Intuitive Surgical, and Johnson & Johnson.

Among patients with stage II or stage III rectal adenocarcinoma, organ preservation is achievable in up to half of patients who undergo total neoadjuvant chemotherapy (TNT), according to the results from a new randomized phase 2 trial.

The study included 324 patients from 18 centers who were randomized into one of two groups: induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT). Patients in both groups then underwent either total mesorectal excision (TME) or a watch-and-wait strategy, depending on tumor response.

“What the study shows is that the order of the chemo and the radiation dose doesn’t affect survival, but it seems to affect the probability of preserving the rectum. That data is consistent with other studies that have compared head-to-head chemotherapy followed by radiation versus radiation followed by chemotherapy. In addition, the survival rate for this study is no different from other prospective studies that included patients with similar-stage tumors selected by MRI. So the data suggest that you can probably avoid surgery in half of the patients with locally advanced rectal cancer and still achieve similar survival compared to patients treated with more conventional neoadjuvant treatments and mandatory surgery,” said lead author Julio Garcia-Aguilar, MD, PhD, in an interview.

“It is a significant shift in the treatment paradigm, that can potentially benefit half of the 50,000 rectal cancer patients diagnosed every year in the United States,” said Dr. Garcia-Aguilar, chief of colorectal surgery at Memorial Sloan Kettering Cancer Center, New York.

The study was published online in the Journal of Clinical Oncology.

Neoadjuvant CRT, TME, and adjuvant chemotherapy is an effective treatment strategy for locally advanced rectal adenocarcinoma, but the regimen can cause bowel, urinary, and sexual dysfunction. The majority of adverse effects from the therapy can be traced to surgery. In addition, some patients with distal rectal cancer often require a permanent colostomy.

TNT is a newer approach that delivers chemotherapy plus radiotherapy before surgery. It is designed to improve treatment compliance and eradicate micrometastases in advance of surgery.

After a median follow-up of 3 years, disease-free survival (76% in both groups) was similar to historical controls (75%). Both groups had similar rates of local recurrence-free survival (94% each) and distant metastasis–free survival (84% for INCT-CRT and 82% for CRT-CNCT).

Following TNT, 26% of patients were recommended for TME, including 28% in the INCT-CRT group and 24% in the CRT-CNCT group, and the rest offered watchful-waiting. Forty percent of those in the INCT-CRT group and 27% in the CRT-CNCT group who went on to watchful waiting had tumor regrowth. Of these combined 75 patients, 67 underwent successful salvage surgery.

In the intention-to-treat analysis, 53% of patients had a preserved rectum at 3 years (95% confidence interval, 45%-62%) in the CRT-CNCT group versus 41% in the INCT-CRT group (95% CI, 33%-50%; P = .01).

The new results reinforce other results and should contribute to shifting clinical practice, according to Dr. Garcia-Aguilar. “I think what we have learned is that rectal cancers respond to chemotherapy and radiation at a higher rate that we thought previously, but that the response takes time. That’s something that we use currently in an adaptive way to modify the treatment as we observe the tumor response,” he said.

The slow regrowth means that patients can be closely monitored without undue risk, but such an approach demands buy-in from the patient. “The patient needs to be compliant with a close surveillance protocol, because otherwise it can be a disaster. I think that’s really part of the message,” Dr. Garcia-Aguilar said.

Dr. Garcia-Aguilar has an ownership interest in Intuitive Surgical and has advised or consulted for Medtronic, Intuitive Surgical, and Johnson & Johnson.

New results from a phase 3 clinical trial may shut the door on the addition of progressive death–1 or PD–ligand 1 inhibitors to the combination of BRAF and MEK inhibitors for the treatment of BRAF V600–mutated melanoma.

The approach seemed promising, given the efficacy of PD-1 and PD-L1 inhibitors in metastatic melanoma, and the relatively short response times to BRAF and MEK inhibitors could potentially be supplemented by longer response times associated with PD-1 and PD-L1 inhibitors. The two categories also have different mechanisms of action and nonoverlapping toxicities, which led to an expectation that the combination would be well tolerated.

But the new study joins two previous randomized, controlled trials that also failed to show much clinical benefit. IMspire150 assigned BRAF V600–mutated melanoma patients to vemurafenib and cobimetinib plus the anti–PD-L1 antibody atezolizumab or placebo. The treatment arm had a small benefit in progression-free survival (hazard ratio, 0.78), which led to Food and Drug Administration approval of the combination, though there was no significant difference when the two cohorts were assessed by an independent review committee. The KEYNOTE-022 trial examined dabrafenib plus trametinib with or without the anti–PD-1 antibody pembrolizumab, and found no difference in investigator-assessed progression free survival.

The new study was published in the Journal of Clinical Oncology. In an accompanying editorial, Margaret K. Callahan, MD, PhD, of Memorial Sloan Kettering Cancer Center, and Paul B. Chapman, MD, of Weill Cornell Medicine, both in New York, speculated that the toxicity of the triplet combination might explain the latest failure, since patients in the triplet arm had more treatment interruptions and dose reductions than the doublet arm (32% received full-dose dabrafenib vs. 54% in the doublet arm), which may have undermined efficacy.

Citing the fact that there are now three randomized, controlled trials with discouraging results, “we believe that there are sufficient data now to be confident that the addition of anti–PD-1 or anti–PD-L1 antibodies to combination RAFi [RAF inhibitors] plus MEKi [MEK inhibitors] is not associated with a significant clinical benefit and should not be studied further in melanoma.

Moreover, “there is some evidence of harm,” the editorial authors wrote. “As the additional toxicity of triplet combination limited the delivery of combination RAFi plus MEKi therapy in COMBI-I. Focus should turn instead to optimizing doses and schedules of combination RAFi plus MEKi and checkpoint inhibitors, developing treatment strategies to overcome resistance to these therapies, and determining how best to sequence combination RAFi plus MEKi therapy and checkpoint inhibitors. Regarding the latter point, there are several sequential therapy trials currently underway in previously untreated patients with BRAF V600–mutated melanoma.”

In the study, patients were randomized to receive dabrafenib and trametinib plus the anti–PD receptor–1 antibody spartalizumab or placebo. After a median follow-up of 27.2 months, mean progression-free survival was 16.2 months in the spartalizumab arm and 12.0 months in the placebo arm (HR, 0.82; P = .042). The spartalizumab group had a 69% objective response rate versus 64% in the placebo group. 55% of the spartalizumab group experienced grade 3 or higher treatment-related adverse events, compared with 33% in the placebo group.

“These results do not support broad use of first-line immunotherapy plus targeted therapy combination, but they provide additional data toward understanding the optimal application of these therapeutic classes in patients with BRAF V600–mutant metastatic melanoma,” the authors of the study wrote.

The study was funded by F Hoffmann–La Roche and Genentech. Dr. Callahan has been employed at Bristol-Myers Squibb, Celgene, and Kleo Pharmaceuticals. Dr. Callahan has consulted for or advised AstraZeneca, Moderna Therapeutics, Merck, and Immunocore. Dr. Chapman has stock or ownership interest in Rgenix; has consulted for or advised Merck, Pfizer, and Black Diamond Therapeutics; and has received research funding from Genentech.

New results from a phase 3 clinical trial may shut the door on the addition of progressive death–1 or PD–ligand 1 inhibitors to the combination of BRAF and MEK inhibitors for the treatment of BRAF V600–mutated melanoma.

The approach seemed promising, given the efficacy of PD-1 and PD-L1 inhibitors in metastatic melanoma, and the relatively short response times to BRAF and MEK inhibitors could potentially be supplemented by longer response times associated with PD-1 and PD-L1 inhibitors. The two categories also have different mechanisms of action and nonoverlapping toxicities, which led to an expectation that the combination would be well tolerated.

But the new study joins two previous randomized, controlled trials that also failed to show much clinical benefit. IMspire150 assigned BRAF V600–mutated melanoma patients to vemurafenib and cobimetinib plus the anti–PD-L1 antibody atezolizumab or placebo. The treatment arm had a small benefit in progression-free survival (hazard ratio, 0.78), which led to Food and Drug Administration approval of the combination, though there was no significant difference when the two cohorts were assessed by an independent review committee. The KEYNOTE-022 trial examined dabrafenib plus trametinib with or without the anti–PD-1 antibody pembrolizumab, and found no difference in investigator-assessed progression free survival.

The new study was published in the Journal of Clinical Oncology. In an accompanying editorial, Margaret K. Callahan, MD, PhD, of Memorial Sloan Kettering Cancer Center, and Paul B. Chapman, MD, of Weill Cornell Medicine, both in New York, speculated that the toxicity of the triplet combination might explain the latest failure, since patients in the triplet arm had more treatment interruptions and dose reductions than the doublet arm (32% received full-dose dabrafenib vs. 54% in the doublet arm), which may have undermined efficacy.

Citing the fact that there are now three randomized, controlled trials with discouraging results, “we believe that there are sufficient data now to be confident that the addition of anti–PD-1 or anti–PD-L1 antibodies to combination RAFi [RAF inhibitors] plus MEKi [MEK inhibitors] is not associated with a significant clinical benefit and should not be studied further in melanoma.

Moreover, “there is some evidence of harm,” the editorial authors wrote. “As the additional toxicity of triplet combination limited the delivery of combination RAFi plus MEKi therapy in COMBI-I. Focus should turn instead to optimizing doses and schedules of combination RAFi plus MEKi and checkpoint inhibitors, developing treatment strategies to overcome resistance to these therapies, and determining how best to sequence combination RAFi plus MEKi therapy and checkpoint inhibitors. Regarding the latter point, there are several sequential therapy trials currently underway in previously untreated patients with BRAF V600–mutated melanoma.”

In the study, patients were randomized to receive dabrafenib and trametinib plus the anti–PD receptor–1 antibody spartalizumab or placebo. After a median follow-up of 27.2 months, mean progression-free survival was 16.2 months in the spartalizumab arm and 12.0 months in the placebo arm (HR, 0.82; P = .042). The spartalizumab group had a 69% objective response rate versus 64% in the placebo group. 55% of the spartalizumab group experienced grade 3 or higher treatment-related adverse events, compared with 33% in the placebo group.

“These results do not support broad use of first-line immunotherapy plus targeted therapy combination, but they provide additional data toward understanding the optimal application of these therapeutic classes in patients with BRAF V600–mutant metastatic melanoma,” the authors of the study wrote.

The study was funded by F Hoffmann–La Roche and Genentech. Dr. Callahan has been employed at Bristol-Myers Squibb, Celgene, and Kleo Pharmaceuticals. Dr. Callahan has consulted for or advised AstraZeneca, Moderna Therapeutics, Merck, and Immunocore. Dr. Chapman has stock or ownership interest in Rgenix; has consulted for or advised Merck, Pfizer, and Black Diamond Therapeutics; and has received research funding from Genentech.

New results from a phase 3 clinical trial may shut the door on the addition of progressive death–1 or PD–ligand 1 inhibitors to the combination of BRAF and MEK inhibitors for the treatment of BRAF V600–mutated melanoma.

The approach seemed promising, given the efficacy of PD-1 and PD-L1 inhibitors in metastatic melanoma, and the relatively short response times to BRAF and MEK inhibitors could potentially be supplemented by longer response times associated with PD-1 and PD-L1 inhibitors. The two categories also have different mechanisms of action and nonoverlapping toxicities, which led to an expectation that the combination would be well tolerated.

But the new study joins two previous randomized, controlled trials that also failed to show much clinical benefit. IMspire150 assigned BRAF V600–mutated melanoma patients to vemurafenib and cobimetinib plus the anti–PD-L1 antibody atezolizumab or placebo. The treatment arm had a small benefit in progression-free survival (hazard ratio, 0.78), which led to Food and Drug Administration approval of the combination, though there was no significant difference when the two cohorts were assessed by an independent review committee. The KEYNOTE-022 trial examined dabrafenib plus trametinib with or without the anti–PD-1 antibody pembrolizumab, and found no difference in investigator-assessed progression free survival.

The new study was published in the Journal of Clinical Oncology. In an accompanying editorial, Margaret K. Callahan, MD, PhD, of Memorial Sloan Kettering Cancer Center, and Paul B. Chapman, MD, of Weill Cornell Medicine, both in New York, speculated that the toxicity of the triplet combination might explain the latest failure, since patients in the triplet arm had more treatment interruptions and dose reductions than the doublet arm (32% received full-dose dabrafenib vs. 54% in the doublet arm), which may have undermined efficacy.

Citing the fact that there are now three randomized, controlled trials with discouraging results, “we believe that there are sufficient data now to be confident that the addition of anti–PD-1 or anti–PD-L1 antibodies to combination RAFi [RAF inhibitors] plus MEKi [MEK inhibitors] is not associated with a significant clinical benefit and should not be studied further in melanoma.

Moreover, “there is some evidence of harm,” the editorial authors wrote. “As the additional toxicity of triplet combination limited the delivery of combination RAFi plus MEKi therapy in COMBI-I. Focus should turn instead to optimizing doses and schedules of combination RAFi plus MEKi and checkpoint inhibitors, developing treatment strategies to overcome resistance to these therapies, and determining how best to sequence combination RAFi plus MEKi therapy and checkpoint inhibitors. Regarding the latter point, there are several sequential therapy trials currently underway in previously untreated patients with BRAF V600–mutated melanoma.”

In the study, patients were randomized to receive dabrafenib and trametinib plus the anti–PD receptor–1 antibody spartalizumab or placebo. After a median follow-up of 27.2 months, mean progression-free survival was 16.2 months in the spartalizumab arm and 12.0 months in the placebo arm (HR, 0.82; P = .042). The spartalizumab group had a 69% objective response rate versus 64% in the placebo group. 55% of the spartalizumab group experienced grade 3 or higher treatment-related adverse events, compared with 33% in the placebo group.

“These results do not support broad use of first-line immunotherapy plus targeted therapy combination, but they provide additional data toward understanding the optimal application of these therapeutic classes in patients with BRAF V600–mutant metastatic melanoma,” the authors of the study wrote.

The study was funded by F Hoffmann–La Roche and Genentech. Dr. Callahan has been employed at Bristol-Myers Squibb, Celgene, and Kleo Pharmaceuticals. Dr. Callahan has consulted for or advised AstraZeneca, Moderna Therapeutics, Merck, and Immunocore. Dr. Chapman has stock or ownership interest in Rgenix; has consulted for or advised Merck, Pfizer, and Black Diamond Therapeutics; and has received research funding from Genentech.

Mastectomies among younger women with nonmetastatic invasive breast cancer may not always be necessary, according to a new study that shows survival outcomes are similar to those of women who had a lumpectomy.

The results come as an increasing number of women under 40 choose mastectomy. “A lot of times, there’s this assumption that removal of the entire breast is going to prevent cancer from returning in that breast. That makes complete sense, it’s intuitive, so I think a lot of patients are surprised to find that less extensive surgery provides the same overall survival as a really extensive surgery,” said Christine Pestana, MD, a fellow in breast surgical oncology with the Atrium Health Levine Cancer Institute, Charlotte, N.C. Dr. Pestana presented the study at the annual meeting of the American Society of Breast Surgeons earlier this year.

In fact, it has been well-demonstrated among women over age 50 with breast cancer that lumpectomy and mastectomy result in similar outcomes, but efforts to show similar efficacy by analyzing data from randomized trials have been limited by small numbers of women under 40, said the study’s lead author Lejla Hadzikadic-Gusic, MD, who is codirector of the Sandra Levine Young Women’s Breast Cancer Program at Atrium Health. “We’ve done a lot of research since the 1970s to be able to keep a woman’s breasts and just treat her for breast cancer. It’s nice to be able to say the same thing for younger women,” said Dr. Hadzikadic-Gusic, in an interview.

The researchers drew from the Young Women’s Database from the Levine Cancer Institute. The analysis included data from nearly 600 women treated between 2010 and 2018.

The increasing frequency of mastectomies in younger women may be traceable, in part, to high-profile cases of celebrities who have had mastectomies after an early breast cancer diagnosis, with Angelina Jolie being among the most known of examples. But Ms. Jolie had the procedure proactively without a cancer diagnosis because she carried the BRCA1 mutation, which increases breast cancer risk. That information was often lost in press coverage, which can lead to confusion among young women with breast cancer, according to Dr. Hadzikadic-Gusic. “What we’re trying to do is have this data help us educate our patients,” she said.

It’s also important for physicians to help guide patients through these decisions, and family history is a key factor. Dr. Pestana encourages primary care providers to explore family history to help understand cancer risks. “It’s not just breast cancer. It’s also ovarian cancer, colon cancer, prostate cancer. Those all have associations with different genetic mutations. If we start asking those questions, we may be able to identify patients who potentially could have that mutation, refer them to a geneticist, have them tested,” she said.

All of the 591 patients in the study were under age 40, with a median age of 37, and the median follow-up was 67 months. Twelve percent of patients died; 53.3% of patients were HR+/HER2–, 20.8% were HR+/HER2+, 19.3% were triple negative, and 6.6% were HR–/HER2+. There was no association between type of surgery and mortality.

The study was funded by the Levine Family Cancer Institute. Dr. Pestana and Dr. Hadzikadic-Gusic have no relevant financial disclosures.

Mastectomies among younger women with nonmetastatic invasive breast cancer may not always be necessary, according to a new study that shows survival outcomes are similar to those of women who had a lumpectomy.

The results come as an increasing number of women under 40 choose mastectomy. “A lot of times, there’s this assumption that removal of the entire breast is going to prevent cancer from returning in that breast. That makes complete sense, it’s intuitive, so I think a lot of patients are surprised to find that less extensive surgery provides the same overall survival as a really extensive surgery,” said Christine Pestana, MD, a fellow in breast surgical oncology with the Atrium Health Levine Cancer Institute, Charlotte, N.C. Dr. Pestana presented the study at the annual meeting of the American Society of Breast Surgeons earlier this year.

In fact, it has been well-demonstrated among women over age 50 with breast cancer that lumpectomy and mastectomy result in similar outcomes, but efforts to show similar efficacy by analyzing data from randomized trials have been limited by small numbers of women under 40, said the study’s lead author Lejla Hadzikadic-Gusic, MD, who is codirector of the Sandra Levine Young Women’s Breast Cancer Program at Atrium Health. “We’ve done a lot of research since the 1970s to be able to keep a woman’s breasts and just treat her for breast cancer. It’s nice to be able to say the same thing for younger women,” said Dr. Hadzikadic-Gusic, in an interview.

The researchers drew from the Young Women’s Database from the Levine Cancer Institute. The analysis included data from nearly 600 women treated between 2010 and 2018.

The increasing frequency of mastectomies in younger women may be traceable, in part, to high-profile cases of celebrities who have had mastectomies after an early breast cancer diagnosis, with Angelina Jolie being among the most known of examples. But Ms. Jolie had the procedure proactively without a cancer diagnosis because she carried the BRCA1 mutation, which increases breast cancer risk. That information was often lost in press coverage, which can lead to confusion among young women with breast cancer, according to Dr. Hadzikadic-Gusic. “What we’re trying to do is have this data help us educate our patients,” she said.

It’s also important for physicians to help guide patients through these decisions, and family history is a key factor. Dr. Pestana encourages primary care providers to explore family history to help understand cancer risks. “It’s not just breast cancer. It’s also ovarian cancer, colon cancer, prostate cancer. Those all have associations with different genetic mutations. If we start asking those questions, we may be able to identify patients who potentially could have that mutation, refer them to a geneticist, have them tested,” she said.

All of the 591 patients in the study were under age 40, with a median age of 37, and the median follow-up was 67 months. Twelve percent of patients died; 53.3% of patients were HR+/HER2–, 20.8% were HR+/HER2+, 19.3% were triple negative, and 6.6% were HR–/HER2+. There was no association between type of surgery and mortality.

The study was funded by the Levine Family Cancer Institute. Dr. Pestana and Dr. Hadzikadic-Gusic have no relevant financial disclosures.

Mastectomies among younger women with nonmetastatic invasive breast cancer may not always be necessary, according to a new study that shows survival outcomes are similar to those of women who had a lumpectomy.

The results come as an increasing number of women under 40 choose mastectomy. “A lot of times, there’s this assumption that removal of the entire breast is going to prevent cancer from returning in that breast. That makes complete sense, it’s intuitive, so I think a lot of patients are surprised to find that less extensive surgery provides the same overall survival as a really extensive surgery,” said Christine Pestana, MD, a fellow in breast surgical oncology with the Atrium Health Levine Cancer Institute, Charlotte, N.C. Dr. Pestana presented the study at the annual meeting of the American Society of Breast Surgeons earlier this year.

In fact, it has been well-demonstrated among women over age 50 with breast cancer that lumpectomy and mastectomy result in similar outcomes, but efforts to show similar efficacy by analyzing data from randomized trials have been limited by small numbers of women under 40, said the study’s lead author Lejla Hadzikadic-Gusic, MD, who is codirector of the Sandra Levine Young Women’s Breast Cancer Program at Atrium Health. “We’ve done a lot of research since the 1970s to be able to keep a woman’s breasts and just treat her for breast cancer. It’s nice to be able to say the same thing for younger women,” said Dr. Hadzikadic-Gusic, in an interview.

The researchers drew from the Young Women’s Database from the Levine Cancer Institute. The analysis included data from nearly 600 women treated between 2010 and 2018.

The increasing frequency of mastectomies in younger women may be traceable, in part, to high-profile cases of celebrities who have had mastectomies after an early breast cancer diagnosis, with Angelina Jolie being among the most known of examples. But Ms. Jolie had the procedure proactively without a cancer diagnosis because she carried the BRCA1 mutation, which increases breast cancer risk. That information was often lost in press coverage, which can lead to confusion among young women with breast cancer, according to Dr. Hadzikadic-Gusic. “What we’re trying to do is have this data help us educate our patients,” she said.

It’s also important for physicians to help guide patients through these decisions, and family history is a key factor. Dr. Pestana encourages primary care providers to explore family history to help understand cancer risks. “It’s not just breast cancer. It’s also ovarian cancer, colon cancer, prostate cancer. Those all have associations with different genetic mutations. If we start asking those questions, we may be able to identify patients who potentially could have that mutation, refer them to a geneticist, have them tested,” she said.

All of the 591 patients in the study were under age 40, with a median age of 37, and the median follow-up was 67 months. Twelve percent of patients died; 53.3% of patients were HR+/HER2–, 20.8% were HR+/HER2+, 19.3% were triple negative, and 6.6% were HR–/HER2+. There was no association between type of surgery and mortality.

The study was funded by the Levine Family Cancer Institute. Dr. Pestana and Dr. Hadzikadic-Gusic have no relevant financial disclosures.

A new study of hospitals in New York City suggests ways to reduce severe maternal morbidity (SMM). The researchers interviewed health care professionals in four institutions with low performance and four with high performance, and identified various themes associated with good performance.

“Our results raise the hypothesis that hospital learning collaboratives focused on optimizing organizational practices and policies, increasing clinician and staff awareness and education on maternal health disparities, and addressing structural racism may be important tools for improving equity in maternal outcomes,” the authors wrote in the study, published in Obstetrics & Gynecology.

The researchers conducted 50 semistructured interviews with health care professionals at lower-performing and higher-performing New York City hospitals, which were selected based on risk-adjusted morbidity metrics. The interviews explored various topics, including structural characteristics like staffing, organizational characteristics like culture and communication, labor and delivery practices such as teamwork and use of evidence-based practices, and racial and ethnic disparities.

The analysis revealed six broad areas that were stronger in high-performing hospitals: day-to-day involvement of leadership in quality activities, an emphasis on standards and standardized care, good communication and teamwork between nurses and physicians, good staffing and supervision among physicians and nurses, sharing of performance data with health care workers, and acknowledgment of the existence of racial and ethnic disparities and that bias can cause treatment differences.

“I think this qualitative approach is an important lens to pair with the quantitative approach. With such variability in severe maternal morbidity between hospitals in New York, it is not enough to just look at the quantitative data. To understand how to improve you must examine structures and processes. The structures, which are the physical and organizational characteristics in health care, and the process, which is how health care is delivered,” Veronica Gillispie-Bell, MD, wrote in a comment. Dr. Gillispie-Bell is medical director at Louisiana Perinatal Quality Collaborative and the Pregnancy-Associated Mortality Review for the Louisiana Department of Health.

“We know that high reliability organizations are those who are preoccupied with quality and safety. That means accountability from leadership (structure) and stability in standardization of care (processes). However, none of this matters if you do not have a culture that promotes safety. Based on the key findings of the high-performing hospitals, there was a culture that promoted safety and quality evidenced in the nurse-physician communication and the transparency around data through a lens of equity,” wrote Dr. Gillispie-Bell.

She noted that the study should encourage low-performing hospitals, since it illustrates avenues for improvement. Her personal experience reflects that, though she said that hospitals need help. The Louisiana Perinatal Quality Collaborative addressed severe maternal morbidity at birthing centers by implementing evidence-based best practices for management of hypertension and hemorrhage along with health equity measures. The team conducted coaching calls, in-person learning sessions, and in-person visits through a “Listening Tour.”

The result was a 35% reduction in hemorrhage overall and a reduction of 49% in hemorrhage in Black women, as well as hypertension by 12% overall between August 2018 and May 2020. Not all the news was good, as Black women still had an increase in severe maternal morbidity, possibly because of the COVID epidemic, since it is a risk factor for hypertension during pregnancy and infection rates are higher among Black individuals. “We need support for state based perinatal quality collaboratives to do this work and we need accountability as we are now seeing from metrics being implemented by [the Centers for Medicare & Medicaid Services]. Hospitals need to stratify their data by race and ethnicity to see where there are disparities in their outcomes,” said Dr. Gillispie-Bell.

The improvements are needed, given that the United States has the highest rates of maternal mortality and morbidity among developed countries, “most of which is preventable, and we have significant inequities by race and ethnicity,” said Laurie Zephyrin, MD, vice president for advancing health equity at the Commonwealth Fund. The question becomes how to effect change, and “there’s a lot happening in the policy space. Some of this policy change is directed at expanding insurance coverage, including more opportunities, including funding for community health workers and doulas, and thinking about how to incorporate midwives. There’s also work around how do we actually improve the care delivered by our health system.” Dr. Zephyrin added that the Department of Health & Human Services has contracted with the health improvement company Premier to use data and best-practices to improve maternal health.

The new work has the potential to be complementary to such approaches. “It provides some structure around how to approach some of the solutions, none of which I think is rocket science. It’s just something that needs to be focused on more intentionally,” said Dr. Zephyrin.

For example, the report found that high-performing hospitals had leaders who collaborated with frontline clinicians to share performance data, and this occurred in person, at departmental quality meetings, and during grand rounds. In contrast, staff in low-performing hospitals did not mention data feedback and some said that their institution made little effort to communicate performance metrics to frontline staff.

“One of the key lessons from the pandemic is that we need to have better data, and we need to have data around race and ethnicity to be able to understand the impact on marginalized communities. This study highlights that there’s more to be done around data to ensure that we can truly move the needle on advancing health equity,” said Dr. Zephyrin.

The researchers also found that clinicians in low-performing institutions did not acknowledge the presence of structural racism or differences in care associated with race or ethnicity. When they acknowledge differences in care, they attributed them to factors outside of the hospital’s control, such as patients not seeking out health care or not maintaining a healthy weight. Clinicians at high-performing hospitals were more likely to explicitly mention racism and bias and acknowledged that these factors could contribute to differences in care.

Dr. Gillispie-Bell and Dr. Zephyrin have no relevant financial disclosures.

A new study of hospitals in New York City suggests ways to reduce severe maternal morbidity (SMM). The researchers interviewed health care professionals in four institutions with low performance and four with high performance, and identified various themes associated with good performance.

“Our results raise the hypothesis that hospital learning collaboratives focused on optimizing organizational practices and policies, increasing clinician and staff awareness and education on maternal health disparities, and addressing structural racism may be important tools for improving equity in maternal outcomes,” the authors wrote in the study, published in Obstetrics & Gynecology.

The researchers conducted 50 semistructured interviews with health care professionals at lower-performing and higher-performing New York City hospitals, which were selected based on risk-adjusted morbidity metrics. The interviews explored various topics, including structural characteristics like staffing, organizational characteristics like culture and communication, labor and delivery practices such as teamwork and use of evidence-based practices, and racial and ethnic disparities.

The analysis revealed six broad areas that were stronger in high-performing hospitals: day-to-day involvement of leadership in quality activities, an emphasis on standards and standardized care, good communication and teamwork between nurses and physicians, good staffing and supervision among physicians and nurses, sharing of performance data with health care workers, and acknowledgment of the existence of racial and ethnic disparities and that bias can cause treatment differences.

“I think this qualitative approach is an important lens to pair with the quantitative approach. With such variability in severe maternal morbidity between hospitals in New York, it is not enough to just look at the quantitative data. To understand how to improve you must examine structures and processes. The structures, which are the physical and organizational characteristics in health care, and the process, which is how health care is delivered,” Veronica Gillispie-Bell, MD, wrote in a comment. Dr. Gillispie-Bell is medical director at Louisiana Perinatal Quality Collaborative and the Pregnancy-Associated Mortality Review for the Louisiana Department of Health.

“We know that high reliability organizations are those who are preoccupied with quality and safety. That means accountability from leadership (structure) and stability in standardization of care (processes). However, none of this matters if you do not have a culture that promotes safety. Based on the key findings of the high-performing hospitals, there was a culture that promoted safety and quality evidenced in the nurse-physician communication and the transparency around data through a lens of equity,” wrote Dr. Gillispie-Bell.

She noted that the study should encourage low-performing hospitals, since it illustrates avenues for improvement. Her personal experience reflects that, though she said that hospitals need help. The Louisiana Perinatal Quality Collaborative addressed severe maternal morbidity at birthing centers by implementing evidence-based best practices for management of hypertension and hemorrhage along with health equity measures. The team conducted coaching calls, in-person learning sessions, and in-person visits through a “Listening Tour.”

The result was a 35% reduction in hemorrhage overall and a reduction of 49% in hemorrhage in Black women, as well as hypertension by 12% overall between August 2018 and May 2020. Not all the news was good, as Black women still had an increase in severe maternal morbidity, possibly because of the COVID epidemic, since it is a risk factor for hypertension during pregnancy and infection rates are higher among Black individuals. “We need support for state based perinatal quality collaboratives to do this work and we need accountability as we are now seeing from metrics being implemented by [the Centers for Medicare & Medicaid Services]. Hospitals need to stratify their data by race and ethnicity to see where there are disparities in their outcomes,” said Dr. Gillispie-Bell.

The improvements are needed, given that the United States has the highest rates of maternal mortality and morbidity among developed countries, “most of which is preventable, and we have significant inequities by race and ethnicity,” said Laurie Zephyrin, MD, vice president for advancing health equity at the Commonwealth Fund. The question becomes how to effect change, and “there’s a lot happening in the policy space. Some of this policy change is directed at expanding insurance coverage, including more opportunities, including funding for community health workers and doulas, and thinking about how to incorporate midwives. There’s also work around how do we actually improve the care delivered by our health system.” Dr. Zephyrin added that the Department of Health & Human Services has contracted with the health improvement company Premier to use data and best-practices to improve maternal health.

The new work has the potential to be complementary to such approaches. “It provides some structure around how to approach some of the solutions, none of which I think is rocket science. It’s just something that needs to be focused on more intentionally,” said Dr. Zephyrin.

For example, the report found that high-performing hospitals had leaders who collaborated with frontline clinicians to share performance data, and this occurred in person, at departmental quality meetings, and during grand rounds. In contrast, staff in low-performing hospitals did not mention data feedback and some said that their institution made little effort to communicate performance metrics to frontline staff.

“One of the key lessons from the pandemic is that we need to have better data, and we need to have data around race and ethnicity to be able to understand the impact on marginalized communities. This study highlights that there’s more to be done around data to ensure that we can truly move the needle on advancing health equity,” said Dr. Zephyrin.

The researchers also found that clinicians in low-performing institutions did not acknowledge the presence of structural racism or differences in care associated with race or ethnicity. When they acknowledge differences in care, they attributed them to factors outside of the hospital’s control, such as patients not seeking out health care or not maintaining a healthy weight. Clinicians at high-performing hospitals were more likely to explicitly mention racism and bias and acknowledged that these factors could contribute to differences in care.

Dr. Gillispie-Bell and Dr. Zephyrin have no relevant financial disclosures.

A new study of hospitals in New York City suggests ways to reduce severe maternal morbidity (SMM). The researchers interviewed health care professionals in four institutions with low performance and four with high performance, and identified various themes associated with good performance.

“Our results raise the hypothesis that hospital learning collaboratives focused on optimizing organizational practices and policies, increasing clinician and staff awareness and education on maternal health disparities, and addressing structural racism may be important tools for improving equity in maternal outcomes,” the authors wrote in the study, published in Obstetrics & Gynecology.

The researchers conducted 50 semistructured interviews with health care professionals at lower-performing and higher-performing New York City hospitals, which were selected based on risk-adjusted morbidity metrics. The interviews explored various topics, including structural characteristics like staffing, organizational characteristics like culture and communication, labor and delivery practices such as teamwork and use of evidence-based practices, and racial and ethnic disparities.

The analysis revealed six broad areas that were stronger in high-performing hospitals: day-to-day involvement of leadership in quality activities, an emphasis on standards and standardized care, good communication and teamwork between nurses and physicians, good staffing and supervision among physicians and nurses, sharing of performance data with health care workers, and acknowledgment of the existence of racial and ethnic disparities and that bias can cause treatment differences.

“I think this qualitative approach is an important lens to pair with the quantitative approach. With such variability in severe maternal morbidity between hospitals in New York, it is not enough to just look at the quantitative data. To understand how to improve you must examine structures and processes. The structures, which are the physical and organizational characteristics in health care, and the process, which is how health care is delivered,” Veronica Gillispie-Bell, MD, wrote in a comment. Dr. Gillispie-Bell is medical director at Louisiana Perinatal Quality Collaborative and the Pregnancy-Associated Mortality Review for the Louisiana Department of Health.

“We know that high reliability organizations are those who are preoccupied with quality and safety. That means accountability from leadership (structure) and stability in standardization of care (processes). However, none of this matters if you do not have a culture that promotes safety. Based on the key findings of the high-performing hospitals, there was a culture that promoted safety and quality evidenced in the nurse-physician communication and the transparency around data through a lens of equity,” wrote Dr. Gillispie-Bell.

She noted that the study should encourage low-performing hospitals, since it illustrates avenues for improvement. Her personal experience reflects that, though she said that hospitals need help. The Louisiana Perinatal Quality Collaborative addressed severe maternal morbidity at birthing centers by implementing evidence-based best practices for management of hypertension and hemorrhage along with health equity measures. The team conducted coaching calls, in-person learning sessions, and in-person visits through a “Listening Tour.”

The result was a 35% reduction in hemorrhage overall and a reduction of 49% in hemorrhage in Black women, as well as hypertension by 12% overall between August 2018 and May 2020. Not all the news was good, as Black women still had an increase in severe maternal morbidity, possibly because of the COVID epidemic, since it is a risk factor for hypertension during pregnancy and infection rates are higher among Black individuals. “We need support for state based perinatal quality collaboratives to do this work and we need accountability as we are now seeing from metrics being implemented by [the Centers for Medicare & Medicaid Services]. Hospitals need to stratify their data by race and ethnicity to see where there are disparities in their outcomes,” said Dr. Gillispie-Bell.

The improvements are needed, given that the United States has the highest rates of maternal mortality and morbidity among developed countries, “most of which is preventable, and we have significant inequities by race and ethnicity,” said Laurie Zephyrin, MD, vice president for advancing health equity at the Commonwealth Fund. The question becomes how to effect change, and “there’s a lot happening in the policy space. Some of this policy change is directed at expanding insurance coverage, including more opportunities, including funding for community health workers and doulas, and thinking about how to incorporate midwives. There’s also work around how do we actually improve the care delivered by our health system.” Dr. Zephyrin added that the Department of Health & Human Services has contracted with the health improvement company Premier to use data and best-practices to improve maternal health.

The new work has the potential to be complementary to such approaches. “It provides some structure around how to approach some of the solutions, none of which I think is rocket science. It’s just something that needs to be focused on more intentionally,” said Dr. Zephyrin.

For example, the report found that high-performing hospitals had leaders who collaborated with frontline clinicians to share performance data, and this occurred in person, at departmental quality meetings, and during grand rounds. In contrast, staff in low-performing hospitals did not mention data feedback and some said that their institution made little effort to communicate performance metrics to frontline staff.

“One of the key lessons from the pandemic is that we need to have better data, and we need to have data around race and ethnicity to be able to understand the impact on marginalized communities. This study highlights that there’s more to be done around data to ensure that we can truly move the needle on advancing health equity,” said Dr. Zephyrin.

The researchers also found that clinicians in low-performing institutions did not acknowledge the presence of structural racism or differences in care associated with race or ethnicity. When they acknowledge differences in care, they attributed them to factors outside of the hospital’s control, such as patients not seeking out health care or not maintaining a healthy weight. Clinicians at high-performing hospitals were more likely to explicitly mention racism and bias and acknowledged that these factors could contribute to differences in care.

Dr. Gillispie-Bell and Dr. Zephyrin have no relevant financial disclosures.

Early-onset colorectal cancer (CRC) affecting patients younger than 50 years has risen sharply since 1988 from 7.9 to 12.9 cases in 2015 per 100,000 people. The reason for the increase isn’t well understood.

The findings were highlighted in a recent review article published online in the New England Journal of Medicine. “It’s a national phenomenon and it’s also occurring in other parts of the developed world. We’re used to seeing mostly older people who have this diagnosis. Now we’re seeing a lot of younger people with this disease. It’s rather alarming,” said author Frank Sinicrope, MD, a medical oncologist with Mayo Clinic, Rochester, Minn.

The trend contrasts with a decline in later-onset CRC likely attributable to increases in screening. As a result of the two trends, but especially the increased number of early-onset cases, the median age of diagnosis dropped from 72 in the early 2000s to 66 today.

“Although patients with early-onset colorectal cancer are more likely to have a hereditary syndrome than those who have later-onset disease, most cases are sporadic, with no identifiable cause. Furthermore, somatic mutational profiling of early-onset colorectal cancers has not revealed previously unidentified or actionable alterations to inform our understanding of the pathogenesis of these cancers or to guide treatment,” he wrote in the review.

“Early-onset colorectal cancers are most commonly detected in the rectum, followed by the distal colon; more than 70% of early-onset colorectal cancers are in the left colon at presentation,” he wrote in the review. Younger patients tend to be unfamiliar with CRC symptoms, which are often mistaken for benign conditions.

“We’ve moved the screening age down to 45, but that still is not going to capture a lot of these patients,” Dr. Sinicrope said. He estimates that 25% of rectal cancers and 10%-12% of colon cancers diagnosed in the next 10 years will be early onset.

Although the direct cause of the increased incidence isn’t clear, Dr. Sinicrope suggested it may reflect changing dietary habits and rising obesity among adolescents. “The sugar-containing beverages, the processed sugar and a lot of red meat in the diet and refined grains … reflect changes in the diet over the last 50 years. We may now be seeing the end result of many of these dietary changes that have occurred,” he said, calling for a greater emphasis on plant-based diets, which promote a healthier gut microbiome that may reduce CRC risk. Western-style diets can change the gut microbiome leading to inflammation which increases the risk of CRC.

Most patients with early CRC present with advanced disease in the left colon. And, pathogenic germline variants are present in one in six patients – half of which are associated with Lynch syndrome which increases the risk for CRC.

Dr. Sinicrope highlighted the need for more risk-based intervention, which in turn requires a better knowledge of family history.

“We need to do better job to risk stratify, and that will help us figure out who’s best to target our screening efforts toward,” Dr. Sinicrope said. He pointed out guidelines from the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society that can help physicians identify patients who might benefit from earlier screening. The American Cancer Society recommends that CRC screening be conducted at 45 years for average-risk individuals.

“The best screening test is the one that the patient will do,” Dr. Sinicrope said.

Early-onset colorectal cancer (CRC) affecting patients younger than 50 years has risen sharply since 1988 from 7.9 to 12.9 cases in 2015 per 100,000 people. The reason for the increase isn’t well understood.

The findings were highlighted in a recent review article published online in the New England Journal of Medicine. “It’s a national phenomenon and it’s also occurring in other parts of the developed world. We’re used to seeing mostly older people who have this diagnosis. Now we’re seeing a lot of younger people with this disease. It’s rather alarming,” said author Frank Sinicrope, MD, a medical oncologist with Mayo Clinic, Rochester, Minn.

The trend contrasts with a decline in later-onset CRC likely attributable to increases in screening. As a result of the two trends, but especially the increased number of early-onset cases, the median age of diagnosis dropped from 72 in the early 2000s to 66 today.

“Although patients with early-onset colorectal cancer are more likely to have a hereditary syndrome than those who have later-onset disease, most cases are sporadic, with no identifiable cause. Furthermore, somatic mutational profiling of early-onset colorectal cancers has not revealed previously unidentified or actionable alterations to inform our understanding of the pathogenesis of these cancers or to guide treatment,” he wrote in the review.

“Early-onset colorectal cancers are most commonly detected in the rectum, followed by the distal colon; more than 70% of early-onset colorectal cancers are in the left colon at presentation,” he wrote in the review. Younger patients tend to be unfamiliar with CRC symptoms, which are often mistaken for benign conditions.

“We’ve moved the screening age down to 45, but that still is not going to capture a lot of these patients,” Dr. Sinicrope said. He estimates that 25% of rectal cancers and 10%-12% of colon cancers diagnosed in the next 10 years will be early onset.

Although the direct cause of the increased incidence isn’t clear, Dr. Sinicrope suggested it may reflect changing dietary habits and rising obesity among adolescents. “The sugar-containing beverages, the processed sugar and a lot of red meat in the diet and refined grains … reflect changes in the diet over the last 50 years. We may now be seeing the end result of many of these dietary changes that have occurred,” he said, calling for a greater emphasis on plant-based diets, which promote a healthier gut microbiome that may reduce CRC risk. Western-style diets can change the gut microbiome leading to inflammation which increases the risk of CRC.

Most patients with early CRC present with advanced disease in the left colon. And, pathogenic germline variants are present in one in six patients – half of which are associated with Lynch syndrome which increases the risk for CRC.

Dr. Sinicrope highlighted the need for more risk-based intervention, which in turn requires a better knowledge of family history.

“We need to do better job to risk stratify, and that will help us figure out who’s best to target our screening efforts toward,” Dr. Sinicrope said. He pointed out guidelines from the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society that can help physicians identify patients who might benefit from earlier screening. The American Cancer Society recommends that CRC screening be conducted at 45 years for average-risk individuals.

“The best screening test is the one that the patient will do,” Dr. Sinicrope said.

Early-onset colorectal cancer (CRC) affecting patients younger than 50 years has risen sharply since 1988 from 7.9 to 12.9 cases in 2015 per 100,000 people. The reason for the increase isn’t well understood.

The findings were highlighted in a recent review article published online in the New England Journal of Medicine. “It’s a national phenomenon and it’s also occurring in other parts of the developed world. We’re used to seeing mostly older people who have this diagnosis. Now we’re seeing a lot of younger people with this disease. It’s rather alarming,” said author Frank Sinicrope, MD, a medical oncologist with Mayo Clinic, Rochester, Minn.

The trend contrasts with a decline in later-onset CRC likely attributable to increases in screening. As a result of the two trends, but especially the increased number of early-onset cases, the median age of diagnosis dropped from 72 in the early 2000s to 66 today.

“Although patients with early-onset colorectal cancer are more likely to have a hereditary syndrome than those who have later-onset disease, most cases are sporadic, with no identifiable cause. Furthermore, somatic mutational profiling of early-onset colorectal cancers has not revealed previously unidentified or actionable alterations to inform our understanding of the pathogenesis of these cancers or to guide treatment,” he wrote in the review.

“Early-onset colorectal cancers are most commonly detected in the rectum, followed by the distal colon; more than 70% of early-onset colorectal cancers are in the left colon at presentation,” he wrote in the review. Younger patients tend to be unfamiliar with CRC symptoms, which are often mistaken for benign conditions.

“We’ve moved the screening age down to 45, but that still is not going to capture a lot of these patients,” Dr. Sinicrope said. He estimates that 25% of rectal cancers and 10%-12% of colon cancers diagnosed in the next 10 years will be early onset.

Although the direct cause of the increased incidence isn’t clear, Dr. Sinicrope suggested it may reflect changing dietary habits and rising obesity among adolescents. “The sugar-containing beverages, the processed sugar and a lot of red meat in the diet and refined grains … reflect changes in the diet over the last 50 years. We may now be seeing the end result of many of these dietary changes that have occurred,” he said, calling for a greater emphasis on plant-based diets, which promote a healthier gut microbiome that may reduce CRC risk. Western-style diets can change the gut microbiome leading to inflammation which increases the risk of CRC.

Most patients with early CRC present with advanced disease in the left colon. And, pathogenic germline variants are present in one in six patients – half of which are associated with Lynch syndrome which increases the risk for CRC.

Dr. Sinicrope highlighted the need for more risk-based intervention, which in turn requires a better knowledge of family history.

“We need to do better job to risk stratify, and that will help us figure out who’s best to target our screening efforts toward,” Dr. Sinicrope said. He pointed out guidelines from the U.S. Multi-Society Task Force on Colorectal Cancer and the American Cancer Society that can help physicians identify patients who might benefit from earlier screening. The American Cancer Society recommends that CRC screening be conducted at 45 years for average-risk individuals.

“The best screening test is the one that the patient will do,” Dr. Sinicrope said.

A qualitative analysis of 20 people with head and neck cancer (HNC) has led to recommendations for improvements in care.

HNC has a high burden of treatment-related adverse events, along with frequent trouble with speech, swallowing, facial disfigurement, and psychological distress.

Among cancer patients, “they have the highest rates of emergency department use and hospitalization during treatment. They also have the highest rates of psychological distress. We have some Ontario data that shows they’ve got the highest rates of suicide and self-harm. So I think this is a really special population that we need to support,” Christopher Noel, MD, PhD, said in an interview. Dr. Noel was the lead author of the study, which was published in JAMA Otolaryngology – Head & Neck Surgery.

These issues can strongly affect quality of life, and even patient outcomes. “Even a 1-day interruption in treatment has been shown to impact oncologic outcomes. This is a very big issue whether you’re a surgeon, a medical oncologist, or a radiation oncologist,” said Dr. Noel, who is a resident physician at the University of Toronto.

He advocates that physicians interview patients and review the results in a structured way and then act on it. “If we just rely on patient [provided] communication, we’re going to miss about 50% of patient symptoms,” he said.

The researchers aimed for the patient’s perspective on treatment. “What is the patient’s perception of going through head neck cancer and their treatment, and managing their symptoms at home? And where do they think that we could do better?” Dr. Noel asked.

The most pressing issue was that patients felt their emotional and informational needs often were not met. That challenge is even harder for patients who have trouble communicating, which in turn makes them more prone to isolation and loneliness. Many felt that they had to get the information on their own. “They wanted it to be a more effortless process,” said Dr. Noel.

He described one patient with oropharynx cancer who was able to talk to people about her grief over her diagnosis, but treatment led to her throat becoming swollen and she lost the ability to communicate. “She felt very isolated and lonely. She really highlighted the emotional and psychosocial barriers in cancer care. Her treatment inherently leaves her feeling very isolated and lonely, and she had such a hard time connecting with a psychotherapist,” Dr. Noel said.

Another common issue revolved around efforts to communicate about symptoms and adverse effects of treatment. Resources often aren’t available on evenings or weekends, and it can take time for a nurse to call them back. Patients wanted to see more modern approaches, such as use of email or apps.

The patients in the study recommended 11 health care improvements.

• 1. Nurse navigator teams should have hours extended to evenings and weekends.
• 2. Patient communication methods should be expanded, using methods like email or apps.
• 3. HNC resources should be more broadly disseminated.
• 4. Education and information approaches should be individualized to the patient.
• 5. All HNC patients should be offered psychological resources.
• 6. Mental health needs should be assessed repeatedly throughout treatment and extended care.
• 7. Physicians should recognize the added symptom burden often faced by patients who travel extensively for treatment.
• 8. Partners and caregivers should be included as part of the treatment team.
• 9. Share symptom data with patients, which can improve engagement.
• 10. Review symptom scores and act on them regularly.
• 11. A member of the care team should be identified to oversee symptom management.

Dr. Noel had no relevant financial disclosures.

A qualitative analysis of 20 people with head and neck cancer (HNC) has led to recommendations for improvements in care.

HNC has a high burden of treatment-related adverse events, along with frequent trouble with speech, swallowing, facial disfigurement, and psychological distress.

Among cancer patients, “they have the highest rates of emergency department use and hospitalization during treatment. They also have the highest rates of psychological distress. We have some Ontario data that shows they’ve got the highest rates of suicide and self-harm. So I think this is a really special population that we need to support,” Christopher Noel, MD, PhD, said in an interview. Dr. Noel was the lead author of the study, which was published in JAMA Otolaryngology – Head & Neck Surgery.

These issues can strongly affect quality of life, and even patient outcomes. “Even a 1-day interruption in treatment has been shown to impact oncologic outcomes. This is a very big issue whether you’re a surgeon, a medical oncologist, or a radiation oncologist,” said Dr. Noel, who is a resident physician at the University of Toronto.

He advocates that physicians interview patients and review the results in a structured way and then act on it. “If we just rely on patient [provided] communication, we’re going to miss about 50% of patient symptoms,” he said.

The researchers aimed for the patient’s perspective on treatment. “What is the patient’s perception of going through head neck cancer and their treatment, and managing their symptoms at home? And where do they think that we could do better?” Dr. Noel asked.

The most pressing issue was that patients felt their emotional and informational needs often were not met. That challenge is even harder for patients who have trouble communicating, which in turn makes them more prone to isolation and loneliness. Many felt that they had to get the information on their own. “They wanted it to be a more effortless process,” said Dr. Noel.

He described one patient with oropharynx cancer who was able to talk to people about her grief over her diagnosis, but treatment led to her throat becoming swollen and she lost the ability to communicate. “She felt very isolated and lonely. She really highlighted the emotional and psychosocial barriers in cancer care. Her treatment inherently leaves her feeling very isolated and lonely, and she had such a hard time connecting with a psychotherapist,” Dr. Noel said.

Another common issue revolved around efforts to communicate about symptoms and adverse effects of treatment. Resources often aren’t available on evenings or weekends, and it can take time for a nurse to call them back. Patients wanted to see more modern approaches, such as use of email or apps.

The patients in the study recommended 11 health care improvements.

• 1. Nurse navigator teams should have hours extended to evenings and weekends.
• 2. Patient communication methods should be expanded, using methods like email or apps.
• 3. HNC resources should be more broadly disseminated.
• 4. Education and information approaches should be individualized to the patient.
• 5. All HNC patients should be offered psychological resources.
• 6. Mental health needs should be assessed repeatedly throughout treatment and extended care.
• 7. Physicians should recognize the added symptom burden often faced by patients who travel extensively for treatment.
• 8. Partners and caregivers should be included as part of the treatment team.
• 9. Share symptom data with patients, which can improve engagement.
• 10. Review symptom scores and act on them regularly.
• 11. A member of the care team should be identified to oversee symptom management.

Dr. Noel had no relevant financial disclosures.

A qualitative analysis of 20 people with head and neck cancer (HNC) has led to recommendations for improvements in care.

HNC has a high burden of treatment-related adverse events, along with frequent trouble with speech, swallowing, facial disfigurement, and psychological distress.

Among cancer patients, “they have the highest rates of emergency department use and hospitalization during treatment. They also have the highest rates of psychological distress. We have some Ontario data that shows they’ve got the highest rates of suicide and self-harm. So I think this is a really special population that we need to support,” Christopher Noel, MD, PhD, said in an interview. Dr. Noel was the lead author of the study, which was published in JAMA Otolaryngology – Head & Neck Surgery.

These issues can strongly affect quality of life, and even patient outcomes. “Even a 1-day interruption in treatment has been shown to impact oncologic outcomes. This is a very big issue whether you’re a surgeon, a medical oncologist, or a radiation oncologist,” said Dr. Noel, who is a resident physician at the University of Toronto.

He advocates that physicians interview patients and review the results in a structured way and then act on it. “If we just rely on patient [provided] communication, we’re going to miss about 50% of patient symptoms,” he said.

The researchers aimed for the patient’s perspective on treatment. “What is the patient’s perception of going through head neck cancer and their treatment, and managing their symptoms at home? And where do they think that we could do better?” Dr. Noel asked.

The most pressing issue was that patients felt their emotional and informational needs often were not met. That challenge is even harder for patients who have trouble communicating, which in turn makes them more prone to isolation and loneliness. Many felt that they had to get the information on their own. “They wanted it to be a more effortless process,” said Dr. Noel.

He described one patient with oropharynx cancer who was able to talk to people about her grief over her diagnosis, but treatment led to her throat becoming swollen and she lost the ability to communicate. “She felt very isolated and lonely. She really highlighted the emotional and psychosocial barriers in cancer care. Her treatment inherently leaves her feeling very isolated and lonely, and she had such a hard time connecting with a psychotherapist,” Dr. Noel said.

Another common issue revolved around efforts to communicate about symptoms and adverse effects of treatment. Resources often aren’t available on evenings or weekends, and it can take time for a nurse to call them back. Patients wanted to see more modern approaches, such as use of email or apps.

The patients in the study recommended 11 health care improvements.

• 1. Nurse navigator teams should have hours extended to evenings and weekends.
• 2. Patient communication methods should be expanded, using methods like email or apps.
• 3. HNC resources should be more broadly disseminated.
• 4. Education and information approaches should be individualized to the patient.
• 5. All HNC patients should be offered psychological resources.
• 6. Mental health needs should be assessed repeatedly throughout treatment and extended care.
• 7. Physicians should recognize the added symptom burden often faced by patients who travel extensively for treatment.
• 8. Partners and caregivers should be included as part of the treatment team.
• 9. Share symptom data with patients, which can improve engagement.
• 10. Review symptom scores and act on them regularly.
• 11. A member of the care team should be identified to oversee symptom management.

Dr. Noel had no relevant financial disclosures.

A mutation in a gene involved in chromatin remodeling is associated with aggressive melanoma, according to a new study that combined in vitro and animal model data.

The gene, ARID2, is a part of the switch/sucrose nonfermentable (SWI/SNF) complex, which maneuvers cellular structures called nucleosomes to make cellular DNA accessible. About 20% of human cancers have a mutation within the SWI/SNF complex.

In the new study, published in Cell Reports, researchers reported that the ARID2 subunit was mutated in about 13% of melanoma patients identified through the Cancer Genome Atlas.

ARID2 mutations have been found in early melanoma lesions, which the authors suggested may play a role in early cancer cell dissemination. Other studies have shown SWI/SNF mutations, including ARID2 mutations, in melanoma metastases, especially the brain.

The researchers also found an up-regulation of synaptic pathways in melanoma cells as well as the Cancer Genome Atlas, which also suggests a potential role of ARID2 loss in metastasis or targeting the brain, since synaptic activation in cancer cells has been shown elsewhere to influence cell migration and survival in the brain.

“We look forward to future studies that investigate the role of the PBAF complex ... in order to better tailor treatments for melanoma patients,” wrote the study authors, who were led by Emily Bernstein, PhD, a professor in oncological sciences with the Icahn School of Medicine at Mount Sinai, New York.

The SWI/SNF complex includes a subcomplex that targets specific DNA sequences or chromatin reader domains. There are multiple versions of the targeting subcomplex, but two of the most frequently occurring are BAF and PBAF. The most commonly mutated subunit in melanoma is ARID2, which is part of PBAF, and contains an AT-rich region responsible for non–sequence-specific DNA interactions. There is evidence that it plays a role in tumor suppression. In mouse tumors, depletion of ARID2 is associated with increased sensitivity to immune checkpoint inhibition and destruction by T cells.

To better understand the role of ARID2 in tumor suppression, the researchers used CRISPR-Cas9 to create ARID2 deficiency in a known human metastatic melanoma cell line. They found there was reduced chromatin accessibility and accompanying gene expression among some PBAF and shared BAF-PBAF–occupied regions. There was also increased chromatin accessibility and gene expression in BAF-occupied regions, and these changes were associated with tumor aggression. In mice, they led to metastasis of distal organs.

This mechanism appears to be conserved between different melanoma cell lines, but deregulated transcriptional targets were different depending on the dominant transcription factors in the cell line. That suggests that the effect of ARID2 mutation or loss may be different depending on the stage of melanoma progression or level of invasiveness. “As melanoma comprises transcriptionally distinct, heterogeneous cell populations, we envision future studies utilizing single-cell methodologies to better understand the nuanced effects of ARID2 loss within subpopulations of cells in human melanoma tumors,” the authors wrote.

The study is limited by the fact that not all ARID2 mutations lead to complete loss of protein, and may lead instead to aberrant complexes.

The study was funded by the National Institutes of Health.

A mutation in a gene involved in chromatin remodeling is associated with aggressive melanoma, according to a new study that combined in vitro and animal model data.

The gene, ARID2, is a part of the switch/sucrose nonfermentable (SWI/SNF) complex, which maneuvers cellular structures called nucleosomes to make cellular DNA accessible. About 20% of human cancers have a mutation within the SWI/SNF complex.

In the new study, published in Cell Reports, researchers reported that the ARID2 subunit was mutated in about 13% of melanoma patients identified through the Cancer Genome Atlas.

ARID2 mutations have been found in early melanoma lesions, which the authors suggested may play a role in early cancer cell dissemination. Other studies have shown SWI/SNF mutations, including ARID2 mutations, in melanoma metastases, especially the brain.

The researchers also found an up-regulation of synaptic pathways in melanoma cells as well as the Cancer Genome Atlas, which also suggests a potential role of ARID2 loss in metastasis or targeting the brain, since synaptic activation in cancer cells has been shown elsewhere to influence cell migration and survival in the brain.

“We look forward to future studies that investigate the role of the PBAF complex ... in order to better tailor treatments for melanoma patients,” wrote the study authors, who were led by Emily Bernstein, PhD, a professor in oncological sciences with the Icahn School of Medicine at Mount Sinai, New York.

The SWI/SNF complex includes a subcomplex that targets specific DNA sequences or chromatin reader domains. There are multiple versions of the targeting subcomplex, but two of the most frequently occurring are BAF and PBAF. The most commonly mutated subunit in melanoma is ARID2, which is part of PBAF, and contains an AT-rich region responsible for non–sequence-specific DNA interactions. There is evidence that it plays a role in tumor suppression. In mouse tumors, depletion of ARID2 is associated with increased sensitivity to immune checkpoint inhibition and destruction by T cells.

To better understand the role of ARID2 in tumor suppression, the researchers used CRISPR-Cas9 to create ARID2 deficiency in a known human metastatic melanoma cell line. They found there was reduced chromatin accessibility and accompanying gene expression among some PBAF and shared BAF-PBAF–occupied regions. There was also increased chromatin accessibility and gene expression in BAF-occupied regions, and these changes were associated with tumor aggression. In mice, they led to metastasis of distal organs.

This mechanism appears to be conserved between different melanoma cell lines, but deregulated transcriptional targets were different depending on the dominant transcription factors in the cell line. That suggests that the effect of ARID2 mutation or loss may be different depending on the stage of melanoma progression or level of invasiveness. “As melanoma comprises transcriptionally distinct, heterogeneous cell populations, we envision future studies utilizing single-cell methodologies to better understand the nuanced effects of ARID2 loss within subpopulations of cells in human melanoma tumors,” the authors wrote.

The study is limited by the fact that not all ARID2 mutations lead to complete loss of protein, and may lead instead to aberrant complexes.

The study was funded by the National Institutes of Health.

A mutation in a gene involved in chromatin remodeling is associated with aggressive melanoma, according to a new study that combined in vitro and animal model data.

The gene, ARID2, is a part of the switch/sucrose nonfermentable (SWI/SNF) complex, which maneuvers cellular structures called nucleosomes to make cellular DNA accessible. About 20% of human cancers have a mutation within the SWI/SNF complex.

In the new study, published in Cell Reports, researchers reported that the ARID2 subunit was mutated in about 13% of melanoma patients identified through the Cancer Genome Atlas.

ARID2 mutations have been found in early melanoma lesions, which the authors suggested may play a role in early cancer cell dissemination. Other studies have shown SWI/SNF mutations, including ARID2 mutations, in melanoma metastases, especially the brain.

The researchers also found an up-regulation of synaptic pathways in melanoma cells as well as the Cancer Genome Atlas, which also suggests a potential role of ARID2 loss in metastasis or targeting the brain, since synaptic activation in cancer cells has been shown elsewhere to influence cell migration and survival in the brain.

“We look forward to future studies that investigate the role of the PBAF complex ... in order to better tailor treatments for melanoma patients,” wrote the study authors, who were led by Emily Bernstein, PhD, a professor in oncological sciences with the Icahn School of Medicine at Mount Sinai, New York.

The SWI/SNF complex includes a subcomplex that targets specific DNA sequences or chromatin reader domains. There are multiple versions of the targeting subcomplex, but two of the most frequently occurring are BAF and PBAF. The most commonly mutated subunit in melanoma is ARID2, which is part of PBAF, and contains an AT-rich region responsible for non–sequence-specific DNA interactions. There is evidence that it plays a role in tumor suppression. In mouse tumors, depletion of ARID2 is associated with increased sensitivity to immune checkpoint inhibition and destruction by T cells.

To better understand the role of ARID2 in tumor suppression, the researchers used CRISPR-Cas9 to create ARID2 deficiency in a known human metastatic melanoma cell line. They found there was reduced chromatin accessibility and accompanying gene expression among some PBAF and shared BAF-PBAF–occupied regions. There was also increased chromatin accessibility and gene expression in BAF-occupied regions, and these changes were associated with tumor aggression. In mice, they led to metastasis of distal organs.

This mechanism appears to be conserved between different melanoma cell lines, but deregulated transcriptional targets were different depending on the dominant transcription factors in the cell line. That suggests that the effect of ARID2 mutation or loss may be different depending on the stage of melanoma progression or level of invasiveness. “As melanoma comprises transcriptionally distinct, heterogeneous cell populations, we envision future studies utilizing single-cell methodologies to better understand the nuanced effects of ARID2 loss within subpopulations of cells in human melanoma tumors,” the authors wrote.

The study is limited by the fact that not all ARID2 mutations lead to complete loss of protein, and may lead instead to aberrant complexes.

The study was funded by the National Institutes of Health.

In an updated clinical practice guideline, the American Society of Clinical Oncology has named the Breast Cancer Index (BCI) as the only genomic test that should be used to guide extended endocrine therapy decisions for women with early-stage, hormone receptor–positive breast cancer. The update applies to women who are node negative or have one to three positive nodes treated with 5 years of endocrine therapy and no sign of recurrence.

The update was published in the Journal of Clinical Oncology. It also gives more specific details on how to apply other, previously recommended, genomic tests to guide treatment choices.

More than half of breast cancer deaths occur after 5 years of tamoxifen therapy. The National Surgical Adjuvant Breast and Bowel Project (NSABP)- B14 trial, published in 2001, showed no benefit to extending tamoxifen therapy to 10 years, but other studies have produced mixed results.

Extended endocrine therapy may reduce the risk of recurrence, but significant side effects can impact quality of life, including osteoporosis, bone fractures, and joint pain. The uncertain benefits of extended endocrine therapy, combined with its side effects and impact on quality of life, has generated interest in genomic tests to identify patients most likely to benefit.

The BCI analyzes 11 genes from the tumor and delivers two results: the likelihood of recurrence 5-10 years after diagnosis, and whether a total of 10 years of endocrine therapy are likely to provide a survival benefit.

The 21-gene prognostic and predictive assay Oncotype DX Breast Recurrence Score, the 70-gene signature test Mammaprint, the 12-gene risk score EndoPredict, levels of Ki67 expression, and immunohistochemistry are also recommended for guiding decisions on endocrine therapy. The update included additional guidance on specific situations that each can be used. However, their usefulness for predicting recurrence at 5-10 years is unproven.

“The clinical decision to either extend or end adjuvant endocrine therapy after 5 years is a challenging decision for healthcare providers and their patients,” Mark Pegram, MD, said in a press release. He is chief medical consultant for breast oncology at Biotheranostics, a subsidiary of Hologic. “There is an extensive body of clinical evidence consistently proving the utility of BCI, and its addition to major oncology clinical guidelines like those from ASCO further underscores the test’s potential in clinical decision-making regarding extended adjuvant endocrine therapy.”

The practice update cited five previous studies showing the ability of BCI to predict benefit from extending endocrine therapy: From 5 years of tamoxifen to 5 more years of tamoxifen; from 5 years of tamoxifen to 5 years of an aromatase inhibitor, and from 5 years of an AI to another 5 years of a drug from the same class. Most of the trials included patients who were node negative or had one to three positive nodes, so there is limited evidence supporting BCI in patients with more than three positive lymph nodes. The recommendation also applies only to postmenopausal women, as the trials included fewer premenopausal and perimenopausal women.

Several of the guideline authors reported conflicts of interest with numerous sources.

In an updated clinical practice guideline, the American Society of Clinical Oncology has named the Breast Cancer Index (BCI) as the only genomic test that should be used to guide extended endocrine therapy decisions for women with early-stage, hormone receptor–positive breast cancer. The update applies to women who are node negative or have one to three positive nodes treated with 5 years of endocrine therapy and no sign of recurrence.

The update was published in the Journal of Clinical Oncology. It also gives more specific details on how to apply other, previously recommended, genomic tests to guide treatment choices.

More than half of breast cancer deaths occur after 5 years of tamoxifen therapy. The National Surgical Adjuvant Breast and Bowel Project (NSABP)- B14 trial, published in 2001, showed no benefit to extending tamoxifen therapy to 10 years, but other studies have produced mixed results.

Extended endocrine therapy may reduce the risk of recurrence, but significant side effects can impact quality of life, including osteoporosis, bone fractures, and joint pain. The uncertain benefits of extended endocrine therapy, combined with its side effects and impact on quality of life, has generated interest in genomic tests to identify patients most likely to benefit.

The BCI analyzes 11 genes from the tumor and delivers two results: the likelihood of recurrence 5-10 years after diagnosis, and whether a total of 10 years of endocrine therapy are likely to provide a survival benefit.

The 21-gene prognostic and predictive assay Oncotype DX Breast Recurrence Score, the 70-gene signature test Mammaprint, the 12-gene risk score EndoPredict, levels of Ki67 expression, and immunohistochemistry are also recommended for guiding decisions on endocrine therapy. The update included additional guidance on specific situations that each can be used. However, their usefulness for predicting recurrence at 5-10 years is unproven.

“The clinical decision to either extend or end adjuvant endocrine therapy after 5 years is a challenging decision for healthcare providers and their patients,” Mark Pegram, MD, said in a press release. He is chief medical consultant for breast oncology at Biotheranostics, a subsidiary of Hologic. “There is an extensive body of clinical evidence consistently proving the utility of BCI, and its addition to major oncology clinical guidelines like those from ASCO further underscores the test’s potential in clinical decision-making regarding extended adjuvant endocrine therapy.”

The practice update cited five previous studies showing the ability of BCI to predict benefit from extending endocrine therapy: From 5 years of tamoxifen to 5 more years of tamoxifen; from 5 years of tamoxifen to 5 years of an aromatase inhibitor, and from 5 years of an AI to another 5 years of a drug from the same class. Most of the trials included patients who were node negative or had one to three positive nodes, so there is limited evidence supporting BCI in patients with more than three positive lymph nodes. The recommendation also applies only to postmenopausal women, as the trials included fewer premenopausal and perimenopausal women.

Several of the guideline authors reported conflicts of interest with numerous sources.

In an updated clinical practice guideline, the American Society of Clinical Oncology has named the Breast Cancer Index (BCI) as the only genomic test that should be used to guide extended endocrine therapy decisions for women with early-stage, hormone receptor–positive breast cancer. The update applies to women who are node negative or have one to three positive nodes treated with 5 years of endocrine therapy and no sign of recurrence.

The update was published in the Journal of Clinical Oncology. It also gives more specific details on how to apply other, previously recommended, genomic tests to guide treatment choices.

More than half of breast cancer deaths occur after 5 years of tamoxifen therapy. The National Surgical Adjuvant Breast and Bowel Project (NSABP)- B14 trial, published in 2001, showed no benefit to extending tamoxifen therapy to 10 years, but other studies have produced mixed results.

Extended endocrine therapy may reduce the risk of recurrence, but significant side effects can impact quality of life, including osteoporosis, bone fractures, and joint pain. The uncertain benefits of extended endocrine therapy, combined with its side effects and impact on quality of life, has generated interest in genomic tests to identify patients most likely to benefit.

The BCI analyzes 11 genes from the tumor and delivers two results: the likelihood of recurrence 5-10 years after diagnosis, and whether a total of 10 years of endocrine therapy are likely to provide a survival benefit.

The 21-gene prognostic and predictive assay Oncotype DX Breast Recurrence Score, the 70-gene signature test Mammaprint, the 12-gene risk score EndoPredict, levels of Ki67 expression, and immunohistochemistry are also recommended for guiding decisions on endocrine therapy. The update included additional guidance on specific situations that each can be used. However, their usefulness for predicting recurrence at 5-10 years is unproven.

“The clinical decision to either extend or end adjuvant endocrine therapy after 5 years is a challenging decision for healthcare providers and their patients,” Mark Pegram, MD, said in a press release. He is chief medical consultant for breast oncology at Biotheranostics, a subsidiary of Hologic. “There is an extensive body of clinical evidence consistently proving the utility of BCI, and its addition to major oncology clinical guidelines like those from ASCO further underscores the test’s potential in clinical decision-making regarding extended adjuvant endocrine therapy.”

The practice update cited five previous studies showing the ability of BCI to predict benefit from extending endocrine therapy: From 5 years of tamoxifen to 5 more years of tamoxifen; from 5 years of tamoxifen to 5 years of an aromatase inhibitor, and from 5 years of an AI to another 5 years of a drug from the same class. Most of the trials included patients who were node negative or had one to three positive nodes, so there is limited evidence supporting BCI in patients with more than three positive lymph nodes. The recommendation also applies only to postmenopausal women, as the trials included fewer premenopausal and perimenopausal women.

Several of the guideline authors reported conflicts of interest with numerous sources.

When it comes to mammography recommendations state comprehensive cancer control (CCC) plans vary considerably and don’t always closely match the U.S. Preventive Services Task Force (USPSTF) recommendations for mammography frequency in women at average risk for breast cancer, according to a new cross-sectional study of CCC plans in all 50 states and the District of Columbia. The recommended age for initiation varied widely among CCC plans, and nearly one in five bore little resemblance at all to the USPTF recommendations.

According to the authors of the study, the variation among suggested ages of initiation may indicate a lack of consensus among state agencies. “For a recommendation tied to service coverage, this is a serious gap in public health policy,” they wrote in the study published online in JAMA Network Open.

CCC plans include goals, measurable objectives, and evidence-based strategies to combat cancers that are both common and preventable. They include input from multiple groups, frequently take 4-6 years to create, and should be updated regularly. Funding from the Centers for Disease Control and Prevention requires that the plans include data cancer screening prevalence rates and specific objectives and strategies.

Breast cancer is the most common cancer in women in the United States, and the second highest cause of cancer death. Regular, high-quality screening reduces breast cancer mortality by 25%-31% among women aged 50-69. As a result, the American Cancer Society, the USPSTF, the American College of Physicians, and the American Academy of Family Physicians have produced guidelines for mammography screening in women at average risk of breast cancer.

Although the benefits of screening are widely accepted, there is disagreement about the ages it should be initiated and ended. These inconsistencies stem from different evidence used to support recommendations, as well as different standards for benefits and harms from screening. Common concerns include overdiagnosis, false-positive results, and radiation damage from mammography.

Because these benefits and harms can vary based on age and values, there is an emphasis on shared decision-making between clinicians and women, especially those aged 40-49.

The most recent USPTF recommendation, issued in 2016, states that women aged 50-74 with average risk should be screened with mammography every 2 years. The choice of mammography in average-risk women under 50 should be approached on an individual basis. USPTF defines average risk as having no signs, symptoms, or previous diagnosis of breast cancer, and no family history or genetic causes for concern.

In the new study, researchers conducted a point-in-time evaluation of CCC plans from 50 states and the District of Columbia, between Nov. 1, 2019, and June 30, 2021.

Thirty-one percent of the plans included the complete USPTF recommendations of biennial mammography between ages 50 and 74; 51% included some, but not all of the USPTF recommendations; and 18% were not consistent at all with USPTF recommendations.

Overall, 59% of plans recommended initiation at age 50 and 37% at age 40, which is consistent with the older 2009 USPSTF recommendation. Eight percent of plans recommended starting at both 40 and 50, and 20% of plans had no recommended age of initiation.

Among the plans that were partially consistent with USPTF, 73% recommended initiation of mammography at age 40 and 31% at age 50. Eighty-five percent did not include an age to stop mammography; 15% did not include a recommended frequency; and 15% had an initiation age other than 40 or 50. Eighty-five percent of plans partially consistent with USPSTF included a recommendation that mammography should be conducted biennially.

The authors state that CCC plans could be improved by a unified emphasis on biennial screening of the general population of women aged 50-74, as well as clear differentiation between women at average risk and those at high risk, who could be screened at ages younger than 50 in consultation with their physician.

The study is limited by the fact that plans were reviewed a single time, while state CCC plans are updated with varying periodicity. The authors agree that implementation of population-based screening should be tailored to individual states and health care systems.

When it comes to mammography recommendations state comprehensive cancer control (CCC) plans vary considerably and don’t always closely match the U.S. Preventive Services Task Force (USPSTF) recommendations for mammography frequency in women at average risk for breast cancer, according to a new cross-sectional study of CCC plans in all 50 states and the District of Columbia. The recommended age for initiation varied widely among CCC plans, and nearly one in five bore little resemblance at all to the USPTF recommendations.

According to the authors of the study, the variation among suggested ages of initiation may indicate a lack of consensus among state agencies. “For a recommendation tied to service coverage, this is a serious gap in public health policy,” they wrote in the study published online in JAMA Network Open.

CCC plans include goals, measurable objectives, and evidence-based strategies to combat cancers that are both common and preventable. They include input from multiple groups, frequently take 4-6 years to create, and should be updated regularly. Funding from the Centers for Disease Control and Prevention requires that the plans include data cancer screening prevalence rates and specific objectives and strategies.

Breast cancer is the most common cancer in women in the United States, and the second highest cause of cancer death. Regular, high-quality screening reduces breast cancer mortality by 25%-31% among women aged 50-69. As a result, the American Cancer Society, the USPSTF, the American College of Physicians, and the American Academy of Family Physicians have produced guidelines for mammography screening in women at average risk of breast cancer.

Although the benefits of screening are widely accepted, there is disagreement about the ages it should be initiated and ended. These inconsistencies stem from different evidence used to support recommendations, as well as different standards for benefits and harms from screening. Common concerns include overdiagnosis, false-positive results, and radiation damage from mammography.

Because these benefits and harms can vary based on age and values, there is an emphasis on shared decision-making between clinicians and women, especially those aged 40-49.

The most recent USPTF recommendation, issued in 2016, states that women aged 50-74 with average risk should be screened with mammography every 2 years. The choice of mammography in average-risk women under 50 should be approached on an individual basis. USPTF defines average risk as having no signs, symptoms, or previous diagnosis of breast cancer, and no family history or genetic causes for concern.

In the new study, researchers conducted a point-in-time evaluation of CCC plans from 50 states and the District of Columbia, between Nov. 1, 2019, and June 30, 2021.

Thirty-one percent of the plans included the complete USPTF recommendations of biennial mammography between ages 50 and 74; 51% included some, but not all of the USPTF recommendations; and 18% were not consistent at all with USPTF recommendations.

Overall, 59% of plans recommended initiation at age 50 and 37% at age 40, which is consistent with the older 2009 USPSTF recommendation. Eight percent of plans recommended starting at both 40 and 50, and 20% of plans had no recommended age of initiation.

Among the plans that were partially consistent with USPTF, 73% recommended initiation of mammography at age 40 and 31% at age 50. Eighty-five percent did not include an age to stop mammography; 15% did not include a recommended frequency; and 15% had an initiation age other than 40 or 50. Eighty-five percent of plans partially consistent with USPSTF included a recommendation that mammography should be conducted biennially.

The authors state that CCC plans could be improved by a unified emphasis on biennial screening of the general population of women aged 50-74, as well as clear differentiation between women at average risk and those at high risk, who could be screened at ages younger than 50 in consultation with their physician.

The study is limited by the fact that plans were reviewed a single time, while state CCC plans are updated with varying periodicity. The authors agree that implementation of population-based screening should be tailored to individual states and health care systems.

When it comes to mammography recommendations state comprehensive cancer control (CCC) plans vary considerably and don’t always closely match the U.S. Preventive Services Task Force (USPSTF) recommendations for mammography frequency in women at average risk for breast cancer, according to a new cross-sectional study of CCC plans in all 50 states and the District of Columbia. The recommended age for initiation varied widely among CCC plans, and nearly one in five bore little resemblance at all to the USPTF recommendations.

According to the authors of the study, the variation among suggested ages of initiation may indicate a lack of consensus among state agencies. “For a recommendation tied to service coverage, this is a serious gap in public health policy,” they wrote in the study published online in JAMA Network Open.

CCC plans include goals, measurable objectives, and evidence-based strategies to combat cancers that are both common and preventable. They include input from multiple groups, frequently take 4-6 years to create, and should be updated regularly. Funding from the Centers for Disease Control and Prevention requires that the plans include data cancer screening prevalence rates and specific objectives and strategies.

Breast cancer is the most common cancer in women in the United States, and the second highest cause of cancer death. Regular, high-quality screening reduces breast cancer mortality by 25%-31% among women aged 50-69. As a result, the American Cancer Society, the USPSTF, the American College of Physicians, and the American Academy of Family Physicians have produced guidelines for mammography screening in women at average risk of breast cancer.

Although the benefits of screening are widely accepted, there is disagreement about the ages it should be initiated and ended. These inconsistencies stem from different evidence used to support recommendations, as well as different standards for benefits and harms from screening. Common concerns include overdiagnosis, false-positive results, and radiation damage from mammography.

Because these benefits and harms can vary based on age and values, there is an emphasis on shared decision-making between clinicians and women, especially those aged 40-49.

The most recent USPTF recommendation, issued in 2016, states that women aged 50-74 with average risk should be screened with mammography every 2 years. The choice of mammography in average-risk women under 50 should be approached on an individual basis. USPTF defines average risk as having no signs, symptoms, or previous diagnosis of breast cancer, and no family history or genetic causes for concern.

In the new study, researchers conducted a point-in-time evaluation of CCC plans from 50 states and the District of Columbia, between Nov. 1, 2019, and June 30, 2021.

Thirty-one percent of the plans included the complete USPTF recommendations of biennial mammography between ages 50 and 74; 51% included some, but not all of the USPTF recommendations; and 18% were not consistent at all with USPTF recommendations.

Overall, 59% of plans recommended initiation at age 50 and 37% at age 40, which is consistent with the older 2009 USPSTF recommendation. Eight percent of plans recommended starting at both 40 and 50, and 20% of plans had no recommended age of initiation.

Among the plans that were partially consistent with USPTF, 73% recommended initiation of mammography at age 40 and 31% at age 50. Eighty-five percent did not include an age to stop mammography; 15% did not include a recommended frequency; and 15% had an initiation age other than 40 or 50. Eighty-five percent of plans partially consistent with USPSTF included a recommendation that mammography should be conducted biennially.

The authors state that CCC plans could be improved by a unified emphasis on biennial screening of the general population of women aged 50-74, as well as clear differentiation between women at average risk and those at high risk, who could be screened at ages younger than 50 in consultation with their physician.

The study is limited by the fact that plans were reviewed a single time, while state CCC plans are updated with varying periodicity. The authors agree that implementation of population-based screening should be tailored to individual states and health care systems.

A rise in esophageal adenocarcinoma (EAC) cases and deaths showcases a need for noninvasive screening methods that can be performed by nonendoscopists, such as nurses or technicians, according to a presentation at the 2022 AGA Tech Summit that reviewed the new approaches. AGA’s annual innovation summit is sponsored by the AGA Center for GI Innovation and Technology.

Mortality rates are high, because the cancer is usually found after obstructive symptoms. Screening for Barrett’s esophagus (BE) and associated dysplasia could lead to earlier diagnosis and better prognoses, but endoscopic screening is costly and invasive, and few at-risk patients take advantage of it.

Some new approaches have the potential to screen more patients and detect earlier stages of disease, according to Prasad Iyer, MD, director of the esophageal interest group in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn.

The estimated rise in EAC ranges from 400% to 600% between 1975 and 2000. The 5-year survival of EAC hovers at around 20%. “Not only is the incidence increasing, but the mortality associated with the disease is also increasing at a similar pace,” said Dr. Iyer during his presentation.

The only known precursor to EAC is BE, which has made the condition a focal point in screening. “If we can screen those with risk factors, we can identify those with prevalent Barrett’s. We then can put those with known Barrett’s into surveillance to detect cancer or high-grade or low-grade dysplasia. And then we when we find dysplasia or early cancer, we can intervene hopefully endoscopically to prevent or treat this progression from Barrett’s to adenocarcinoma,” said Dr. Iyer.

Endoscopic treatment of dysplasia achieves similar long-term survival outcomes to esophagectomy,Dr. Iyer said. Clinical studies have shown that radiofrequency ablation of high-grade and low-grade dysplasia reduces progression to cancer.
 

Low screening rates miss at-risk patients

Unfortunately, only 10%-12% of esophageal cancers are detected during surveillance, partly because many with BE are unaware of the condition and therefore don’t enter surveillance. “Two-thirds of the patients with Barrett’s are not under surveillance, so it’s not surprising that most esophageal cancers, unfortunately, are still being diagnosed after the onset of obstructive symptoms,” said Dr. Iyer.

A key issue is that sedated endoscopy is the only available screening tool, and it is expensive and invasive. “Only 10% of those who should get evaluated for the presence of Barrett’s are currently getting evaluated,” said Dr. Iyer.

Those issues have led to a movement to develop noninvasive methods for screening that could be performed by nonendoscopists, such as nurses or technicians. Dr. Iyer noted the importance of sensitivity and specificity of any test, but access to the test and participation are often overlooked factors.

“We hope that, by developing a nonendoscopic, minimally invasive test, we can increase access by allowing nonphysicians to perform this test. By keeping the costs low, we make this strategy cost effective, and hopefully get buy in for reimbursement from payers,” said Dr. Iyer.
 

New screening methods on horizon

He reviewed several noninvasive screening methodologies in development.

Unsedated transnasal endoscopy has been used successfully to diagnose BE, but the technique has not gained much traction in the United States.

Some devices collect esophageal cells, and then test them for various biomarkers. These include EsophaCap, CytoSponge, and the ESOCHEK Balloon. The procedure requires the patient to swallow a device, which is attached to a string or cord. After a few minutes, the device expands into a sphere or balloon, and the operator pulls it out through the esophagus, collecting 3-4 million esophageal cells in the process.

Biomarker analysis of the cells can include the protein trefoil factor 3 and methylated DNA markers. Case-control studies have shown this approach can achieve sensitivities of 76%-94%, and specificities of 62%-92%. “At least in case-control studies, this technology has been shown in thousands of patients now to be well tolerated, very safe, with a low risk of detachment, and can be done by a nurse in an office setting in less than 10 minutes,” said Dr. Iyer.
 

Earlier detection of Barrett’s

He summarized a randomized, controlled trial, published in 2020 in The Lancet, which tested this approach in patients who had taken proton pump inhibitors for at least 6 months. It compared 6,983 patients screened using the CytoSponge/TFF3 with 6,531 usual-care patients who only underwent screening if their physicians recommended it.

In the screening group, 140 patients were diagnosed with Barrett’s Esophagus, compared with 13 in the usual-care group. There were nine cases of dysplastic Barrett’s and five cases of stage I EAC in the screening group, versus no dysplastic Barrett’s and three advanced stage EAC cases in the usual care group. “You can see how we can shift the spectrum of patients with Barrett’s if we go for early detection,” said Dr. Iyer.

Another noninvasive strategy relies on sensors to detect exhaled volatile organic compounds. After a patient breathes into the detector for about 5 minutes, an artificial neural network distinguishes molecular patterns indicative of the presence or absence of BE. The technique had just moderate sensitivity and specificity, “But this is very noninvasive and even less invasive than [sponge or balloon]-based technology,” said Dr. Iyer.

Other efforts are underway to identify plasma biomarkers for screening. Dr. Iyer and colleagues have developed methylated DNA markers for EAC and squamous cell cancer. So far, they have achieved sensitivity and specificity just above 80%. “Not where we would want it to be, but certainly not terrible,” said Dr. Iyer, adding that they are performing a larger prospective study.

He described a potential screening program that could draw from electronic medical records or even apps to identify patients with risk above a defined threshold who would then be tested with minimally invasive techniques. Those with positive results would go on to confirmatory endoscopy. His group found that such a strategy would be cost effective even if reflux was not used as a qualifying criterion for screening.

Answering audience questions after the talk, Dr. Iyer was asked if noninvasive methods would directly compete with endoscopy, or if some patients would be better candidates for one or the other.

“That’s something we need to think through. It’s going to be very difficult for us to say every patient at risk should get an endoscopy. I just don’t think that strategy is probably practical or cost effective. On the other hand, I think an all-of-the-above strategy is probably just fine. It’s like elections. You have to be very local, your message has to be cost effective, available, and have adequate patient as well as provider buy-in,” he said.

Dr. Iyer has received research funding from Exact Sciences, Pentax Medical, and Cernostics. He has consulted for Exact Sciences, Pentax Medical, Medtronic, Ambu, Cernostics, CDx Diagnostics, and Symple Surgical. The 2022 AGA Tech Summit was supported by independent grants from Castle Biosciences, Medtronic, Boston Scientific, Exact Sciences, Olympus, 3-D Matrix, Apollo Endosurgery, Motus GI Holdings, STERIS Endoscopy, Cook Medical, FUJIFILM Healthcare Americas, and Virgo.

This article was updated 5/10/22.

A rise in esophageal adenocarcinoma (EAC) cases and deaths showcases a need for noninvasive screening methods that can be performed by nonendoscopists, such as nurses or technicians, according to a presentation at the 2022 AGA Tech Summit that reviewed the new approaches. AGA’s annual innovation summit is sponsored by the AGA Center for GI Innovation and Technology.

Mortality rates are high, because the cancer is usually found after obstructive symptoms. Screening for Barrett’s esophagus (BE) and associated dysplasia could lead to earlier diagnosis and better prognoses, but endoscopic screening is costly and invasive, and few at-risk patients take advantage of it.

Some new approaches have the potential to screen more patients and detect earlier stages of disease, according to Prasad Iyer, MD, director of the esophageal interest group in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn.

The estimated rise in EAC ranges from 400% to 600% between 1975 and 2000. The 5-year survival of EAC hovers at around 20%. “Not only is the incidence increasing, but the mortality associated with the disease is also increasing at a similar pace,” said Dr. Iyer during his presentation.

The only known precursor to EAC is BE, which has made the condition a focal point in screening. “If we can screen those with risk factors, we can identify those with prevalent Barrett’s. We then can put those with known Barrett’s into surveillance to detect cancer or high-grade or low-grade dysplasia. And then we when we find dysplasia or early cancer, we can intervene hopefully endoscopically to prevent or treat this progression from Barrett’s to adenocarcinoma,” said Dr. Iyer.

Endoscopic treatment of dysplasia achieves similar long-term survival outcomes to esophagectomy,Dr. Iyer said. Clinical studies have shown that radiofrequency ablation of high-grade and low-grade dysplasia reduces progression to cancer.
 

Low screening rates miss at-risk patients

Unfortunately, only 10%-12% of esophageal cancers are detected during surveillance, partly because many with BE are unaware of the condition and therefore don’t enter surveillance. “Two-thirds of the patients with Barrett’s are not under surveillance, so it’s not surprising that most esophageal cancers, unfortunately, are still being diagnosed after the onset of obstructive symptoms,” said Dr. Iyer.

A key issue is that sedated endoscopy is the only available screening tool, and it is expensive and invasive. “Only 10% of those who should get evaluated for the presence of Barrett’s are currently getting evaluated,” said Dr. Iyer.

Those issues have led to a movement to develop noninvasive methods for screening that could be performed by nonendoscopists, such as nurses or technicians. Dr. Iyer noted the importance of sensitivity and specificity of any test, but access to the test and participation are often overlooked factors.

“We hope that, by developing a nonendoscopic, minimally invasive test, we can increase access by allowing nonphysicians to perform this test. By keeping the costs low, we make this strategy cost effective, and hopefully get buy in for reimbursement from payers,” said Dr. Iyer.
 

New screening methods on horizon

He reviewed several noninvasive screening methodologies in development.

Unsedated transnasal endoscopy has been used successfully to diagnose BE, but the technique has not gained much traction in the United States.

Some devices collect esophageal cells, and then test them for various biomarkers. These include EsophaCap, CytoSponge, and the ESOCHEK Balloon. The procedure requires the patient to swallow a device, which is attached to a string or cord. After a few minutes, the device expands into a sphere or balloon, and the operator pulls it out through the esophagus, collecting 3-4 million esophageal cells in the process.

Biomarker analysis of the cells can include the protein trefoil factor 3 and methylated DNA markers. Case-control studies have shown this approach can achieve sensitivities of 76%-94%, and specificities of 62%-92%. “At least in case-control studies, this technology has been shown in thousands of patients now to be well tolerated, very safe, with a low risk of detachment, and can be done by a nurse in an office setting in less than 10 minutes,” said Dr. Iyer.
 

Earlier detection of Barrett’s

He summarized a randomized, controlled trial, published in 2020 in The Lancet, which tested this approach in patients who had taken proton pump inhibitors for at least 6 months. It compared 6,983 patients screened using the CytoSponge/TFF3 with 6,531 usual-care patients who only underwent screening if their physicians recommended it.

In the screening group, 140 patients were diagnosed with Barrett’s Esophagus, compared with 13 in the usual-care group. There were nine cases of dysplastic Barrett’s and five cases of stage I EAC in the screening group, versus no dysplastic Barrett’s and three advanced stage EAC cases in the usual care group. “You can see how we can shift the spectrum of patients with Barrett’s if we go for early detection,” said Dr. Iyer.

Another noninvasive strategy relies on sensors to detect exhaled volatile organic compounds. After a patient breathes into the detector for about 5 minutes, an artificial neural network distinguishes molecular patterns indicative of the presence or absence of BE. The technique had just moderate sensitivity and specificity, “But this is very noninvasive and even less invasive than [sponge or balloon]-based technology,” said Dr. Iyer.

Other efforts are underway to identify plasma biomarkers for screening. Dr. Iyer and colleagues have developed methylated DNA markers for EAC and squamous cell cancer. So far, they have achieved sensitivity and specificity just above 80%. “Not where we would want it to be, but certainly not terrible,” said Dr. Iyer, adding that they are performing a larger prospective study.

He described a potential screening program that could draw from electronic medical records or even apps to identify patients with risk above a defined threshold who would then be tested with minimally invasive techniques. Those with positive results would go on to confirmatory endoscopy. His group found that such a strategy would be cost effective even if reflux was not used as a qualifying criterion for screening.

Answering audience questions after the talk, Dr. Iyer was asked if noninvasive methods would directly compete with endoscopy, or if some patients would be better candidates for one or the other.

“That’s something we need to think through. It’s going to be very difficult for us to say every patient at risk should get an endoscopy. I just don’t think that strategy is probably practical or cost effective. On the other hand, I think an all-of-the-above strategy is probably just fine. It’s like elections. You have to be very local, your message has to be cost effective, available, and have adequate patient as well as provider buy-in,” he said.

Dr. Iyer has received research funding from Exact Sciences, Pentax Medical, and Cernostics. He has consulted for Exact Sciences, Pentax Medical, Medtronic, Ambu, Cernostics, CDx Diagnostics, and Symple Surgical. The 2022 AGA Tech Summit was supported by independent grants from Castle Biosciences, Medtronic, Boston Scientific, Exact Sciences, Olympus, 3-D Matrix, Apollo Endosurgery, Motus GI Holdings, STERIS Endoscopy, Cook Medical, FUJIFILM Healthcare Americas, and Virgo.

This article was updated 5/10/22.

A rise in esophageal adenocarcinoma (EAC) cases and deaths showcases a need for noninvasive screening methods that can be performed by nonendoscopists, such as nurses or technicians, according to a presentation at the 2022 AGA Tech Summit that reviewed the new approaches. AGA’s annual innovation summit is sponsored by the AGA Center for GI Innovation and Technology.

Mortality rates are high, because the cancer is usually found after obstructive symptoms. Screening for Barrett’s esophagus (BE) and associated dysplasia could lead to earlier diagnosis and better prognoses, but endoscopic screening is costly and invasive, and few at-risk patients take advantage of it.

Some new approaches have the potential to screen more patients and detect earlier stages of disease, according to Prasad Iyer, MD, director of the esophageal interest group in the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn.

The estimated rise in EAC ranges from 400% to 600% between 1975 and 2000. The 5-year survival of EAC hovers at around 20%. “Not only is the incidence increasing, but the mortality associated with the disease is also increasing at a similar pace,” said Dr. Iyer during his presentation.

The only known precursor to EAC is BE, which has made the condition a focal point in screening. “If we can screen those with risk factors, we can identify those with prevalent Barrett’s. We then can put those with known Barrett’s into surveillance to detect cancer or high-grade or low-grade dysplasia. And then we when we find dysplasia or early cancer, we can intervene hopefully endoscopically to prevent or treat this progression from Barrett’s to adenocarcinoma,” said Dr. Iyer.

Endoscopic treatment of dysplasia achieves similar long-term survival outcomes to esophagectomy,Dr. Iyer said. Clinical studies have shown that radiofrequency ablation of high-grade and low-grade dysplasia reduces progression to cancer.
 

Low screening rates miss at-risk patients

Unfortunately, only 10%-12% of esophageal cancers are detected during surveillance, partly because many with BE are unaware of the condition and therefore don’t enter surveillance. “Two-thirds of the patients with Barrett’s are not under surveillance, so it’s not surprising that most esophageal cancers, unfortunately, are still being diagnosed after the onset of obstructive symptoms,” said Dr. Iyer.

A key issue is that sedated endoscopy is the only available screening tool, and it is expensive and invasive. “Only 10% of those who should get evaluated for the presence of Barrett’s are currently getting evaluated,” said Dr. Iyer.

Those issues have led to a movement to develop noninvasive methods for screening that could be performed by nonendoscopists, such as nurses or technicians. Dr. Iyer noted the importance of sensitivity and specificity of any test, but access to the test and participation are often overlooked factors.

“We hope that, by developing a nonendoscopic, minimally invasive test, we can increase access by allowing nonphysicians to perform this test. By keeping the costs low, we make this strategy cost effective, and hopefully get buy in for reimbursement from payers,” said Dr. Iyer.
 

New screening methods on horizon

He reviewed several noninvasive screening methodologies in development.

Unsedated transnasal endoscopy has been used successfully to diagnose BE, but the technique has not gained much traction in the United States.

Some devices collect esophageal cells, and then test them for various biomarkers. These include EsophaCap, CytoSponge, and the ESOCHEK Balloon. The procedure requires the patient to swallow a device, which is attached to a string or cord. After a few minutes, the device expands into a sphere or balloon, and the operator pulls it out through the esophagus, collecting 3-4 million esophageal cells in the process.

Biomarker analysis of the cells can include the protein trefoil factor 3 and methylated DNA markers. Case-control studies have shown this approach can achieve sensitivities of 76%-94%, and specificities of 62%-92%. “At least in case-control studies, this technology has been shown in thousands of patients now to be well tolerated, very safe, with a low risk of detachment, and can be done by a nurse in an office setting in less than 10 minutes,” said Dr. Iyer.
 

Earlier detection of Barrett’s

He summarized a randomized, controlled trial, published in 2020 in The Lancet, which tested this approach in patients who had taken proton pump inhibitors for at least 6 months. It compared 6,983 patients screened using the CytoSponge/TFF3 with 6,531 usual-care patients who only underwent screening if their physicians recommended it.

In the screening group, 140 patients were diagnosed with Barrett’s Esophagus, compared with 13 in the usual-care group. There were nine cases of dysplastic Barrett’s and five cases of stage I EAC in the screening group, versus no dysplastic Barrett’s and three advanced stage EAC cases in the usual care group. “You can see how we can shift the spectrum of patients with Barrett’s if we go for early detection,” said Dr. Iyer.

Another noninvasive strategy relies on sensors to detect exhaled volatile organic compounds. After a patient breathes into the detector for about 5 minutes, an artificial neural network distinguishes molecular patterns indicative of the presence or absence of BE. The technique had just moderate sensitivity and specificity, “But this is very noninvasive and even less invasive than [sponge or balloon]-based technology,” said Dr. Iyer.

Other efforts are underway to identify plasma biomarkers for screening. Dr. Iyer and colleagues have developed methylated DNA markers for EAC and squamous cell cancer. So far, they have achieved sensitivity and specificity just above 80%. “Not where we would want it to be, but certainly not terrible,” said Dr. Iyer, adding that they are performing a larger prospective study.

He described a potential screening program that could draw from electronic medical records or even apps to identify patients with risk above a defined threshold who would then be tested with minimally invasive techniques. Those with positive results would go on to confirmatory endoscopy. His group found that such a strategy would be cost effective even if reflux was not used as a qualifying criterion for screening.

Answering audience questions after the talk, Dr. Iyer was asked if noninvasive methods would directly compete with endoscopy, or if some patients would be better candidates for one or the other.

“That’s something we need to think through. It’s going to be very difficult for us to say every patient at risk should get an endoscopy. I just don’t think that strategy is probably practical or cost effective. On the other hand, I think an all-of-the-above strategy is probably just fine. It’s like elections. You have to be very local, your message has to be cost effective, available, and have adequate patient as well as provider buy-in,” he said.

Dr. Iyer has received research funding from Exact Sciences, Pentax Medical, and Cernostics. He has consulted for Exact Sciences, Pentax Medical, Medtronic, Ambu, Cernostics, CDx Diagnostics, and Symple Surgical. The 2022 AGA Tech Summit was supported by independent grants from Castle Biosciences, Medtronic, Boston Scientific, Exact Sciences, Olympus, 3-D Matrix, Apollo Endosurgery, Motus GI Holdings, STERIS Endoscopy, Cook Medical, FUJIFILM Healthcare Americas, and Virgo.

This article was updated 5/10/22.