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Endoscopic mucosal resection valuable for cancer diagnosis
said a physician presenting at the 2022 Gastrointestinal Cancers Symposium.
Vani Konda, MD, a gastroenterologist with Baylor Scott and White Center for Esophageal Diseases, Dallas, participated in an educational session on approaches for treating localized gastroesophageal cancer. In her presentation, she addressed the advantages and disadvantages of EMR and endoscopic submucosal dissection (ESD) for esophageal neoplasia for both diagnosis and treatment.
Esophageal neoplasia therapy includes tissue-acquiring (lesion removal and histopathologic samples) and non–tissue-acquiring therapies (which include radiofrequency ablation, cryotherapy and hybrid-argon plasma coagulation.
The optimal therapy may vary with the esophageal cancer, and the cancer may vary with geography. Worldwide, squamous cell carcinoma is predominant, while in Western countries, esophageal adenocarcinoma is most prevalent. The incidence and mortality of esophageal adenocarcinoma has been rising for several decades, Dr. Konda said.
Considering risk factors
Barrett’s esophagus is a known risk factor for esophageal adenocarcinoma. It can be seen endoscopically as salmon-colored lining, and histologically as specialized intestinal metaplasia.
A lesion extending beyond the basement membrane into the lamina propria is an intramucosal carcinoma, or T1a lesion. A lesion extending beyond the muscularis mucosa into the submucosa is a submucosal carcinoma, or T1b tumor, Dr. Konda said.
“The difference between T1a and T1b is important in the selection of treatment approaches due to the risk of [lymph node] metastasis,” she said. She equated a T1a lesion with a 2% or smaller risk of lymph node metastasis, and a T1b tumor with a 20% risk.*
Endoscopic therapy is more reasonable for a T1a lesion, especially since the alternative, esophagectomy, may have a mortality rate of 2% or higher, she said, while for T1b tumors, surgical or systemic treatments are warranted.
A diagnosis of high-grade dysplasia by biopsy is associated with a 40% risk of prevalent cancer, mostly intramucosal carcinoma. On the other hand, submucosal carcinoma is rare in the absence of endoscopically visible lesions. “This risk of prevalent cancer, especially in visible lesions, is the reason that we should address all visible lesions with endoscopic resection, especially in the setting of dysplasia,” Dr. Konda said.
EMR is more accurate than biopsies; diagnoses change up to half the time when EMR is done after a preresection biopsy, and there’s a higher interobserver agreement among pathologists with EMR, she said.
The goal of therapy in Barrett’s esophagus is total Barrett’s eradication to treat not only the known neoplasia, but also the rest of the at-risk epithelium.
Piecemeal EMR for the entire Barrett’s epithelium can bring about a 96% or greater neoplasia eradication rate. But the stricture rate may reach 37%, and bleeding and perforation are also common.
Combining endoscopic mucosal resection for visible lesions with ablation for the rest of the at-risk lining can achieve an eradication rate of 93% with a more favorable complication profile.
Weighing the benefits of ESD
In contrast to EMR, ESD has been practiced more frequently in Asia. It provides an en bloc specimen.
A 2014 systematic review of 380 EMR procedures and 333 ESD procedures for Barret’s associated neoplasia indicated that ESD takes longer. The recurrence rate was 0.7% for ESD versus 2.6% for EMR, but this difference fell just short of statistical significance (P = .06). Bleeding and perforation rates were similar, but stricture rates reached 22.3% with wide-field EMR, 3.4% with ESD and 0.7% with focal EMR.
In a 2016 head-to-head trial, researchers assigned 20 patients each to EMR or ESD. They found the procedure longer, but the en bloc resection was higher in ESD. Complete remission of the neoplasia was not statistically different between the two groups, with 15 of 16 patients achieving this goal with ESD and 16 of 17 with EMR. All the patients had complete remission after one retreatment of residual neoplasia. There were two severe adverse events in the ESD group, and none in the EMR group.
Weighing the pros and cons, Dr. Konda concluded that EMR is technically easier and adequate in most cases of Barrett’s esophagus, while ESD may be preferred in select cases with concern for submucosal carcinoma or nonlifting lesions.
She advocated taking patient characteristics, disease characteristics, and available expertise into account.
Dr. Konda reported financial relationships with Ambu, Cernostics, Exact Sciences, Medtronic, and Lucid Sciences. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
*Correction, 1/28/22: An earlier version of this article mischaracterized lymph node metastasis.
said a physician presenting at the 2022 Gastrointestinal Cancers Symposium.
Vani Konda, MD, a gastroenterologist with Baylor Scott and White Center for Esophageal Diseases, Dallas, participated in an educational session on approaches for treating localized gastroesophageal cancer. In her presentation, she addressed the advantages and disadvantages of EMR and endoscopic submucosal dissection (ESD) for esophageal neoplasia for both diagnosis and treatment.
Esophageal neoplasia therapy includes tissue-acquiring (lesion removal and histopathologic samples) and non–tissue-acquiring therapies (which include radiofrequency ablation, cryotherapy and hybrid-argon plasma coagulation.
The optimal therapy may vary with the esophageal cancer, and the cancer may vary with geography. Worldwide, squamous cell carcinoma is predominant, while in Western countries, esophageal adenocarcinoma is most prevalent. The incidence and mortality of esophageal adenocarcinoma has been rising for several decades, Dr. Konda said.
Considering risk factors
Barrett’s esophagus is a known risk factor for esophageal adenocarcinoma. It can be seen endoscopically as salmon-colored lining, and histologically as specialized intestinal metaplasia.
A lesion extending beyond the basement membrane into the lamina propria is an intramucosal carcinoma, or T1a lesion. A lesion extending beyond the muscularis mucosa into the submucosa is a submucosal carcinoma, or T1b tumor, Dr. Konda said.
“The difference between T1a and T1b is important in the selection of treatment approaches due to the risk of [lymph node] metastasis,” she said. She equated a T1a lesion with a 2% or smaller risk of lymph node metastasis, and a T1b tumor with a 20% risk.*
Endoscopic therapy is more reasonable for a T1a lesion, especially since the alternative, esophagectomy, may have a mortality rate of 2% or higher, she said, while for T1b tumors, surgical or systemic treatments are warranted.
A diagnosis of high-grade dysplasia by biopsy is associated with a 40% risk of prevalent cancer, mostly intramucosal carcinoma. On the other hand, submucosal carcinoma is rare in the absence of endoscopically visible lesions. “This risk of prevalent cancer, especially in visible lesions, is the reason that we should address all visible lesions with endoscopic resection, especially in the setting of dysplasia,” Dr. Konda said.
EMR is more accurate than biopsies; diagnoses change up to half the time when EMR is done after a preresection biopsy, and there’s a higher interobserver agreement among pathologists with EMR, she said.
The goal of therapy in Barrett’s esophagus is total Barrett’s eradication to treat not only the known neoplasia, but also the rest of the at-risk epithelium.
Piecemeal EMR for the entire Barrett’s epithelium can bring about a 96% or greater neoplasia eradication rate. But the stricture rate may reach 37%, and bleeding and perforation are also common.
Combining endoscopic mucosal resection for visible lesions with ablation for the rest of the at-risk lining can achieve an eradication rate of 93% with a more favorable complication profile.
Weighing the benefits of ESD
In contrast to EMR, ESD has been practiced more frequently in Asia. It provides an en bloc specimen.
A 2014 systematic review of 380 EMR procedures and 333 ESD procedures for Barret’s associated neoplasia indicated that ESD takes longer. The recurrence rate was 0.7% for ESD versus 2.6% for EMR, but this difference fell just short of statistical significance (P = .06). Bleeding and perforation rates were similar, but stricture rates reached 22.3% with wide-field EMR, 3.4% with ESD and 0.7% with focal EMR.
In a 2016 head-to-head trial, researchers assigned 20 patients each to EMR or ESD. They found the procedure longer, but the en bloc resection was higher in ESD. Complete remission of the neoplasia was not statistically different between the two groups, with 15 of 16 patients achieving this goal with ESD and 16 of 17 with EMR. All the patients had complete remission after one retreatment of residual neoplasia. There were two severe adverse events in the ESD group, and none in the EMR group.
Weighing the pros and cons, Dr. Konda concluded that EMR is technically easier and adequate in most cases of Barrett’s esophagus, while ESD may be preferred in select cases with concern for submucosal carcinoma or nonlifting lesions.
She advocated taking patient characteristics, disease characteristics, and available expertise into account.
Dr. Konda reported financial relationships with Ambu, Cernostics, Exact Sciences, Medtronic, and Lucid Sciences. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
*Correction, 1/28/22: An earlier version of this article mischaracterized lymph node metastasis.
said a physician presenting at the 2022 Gastrointestinal Cancers Symposium.
Vani Konda, MD, a gastroenterologist with Baylor Scott and White Center for Esophageal Diseases, Dallas, participated in an educational session on approaches for treating localized gastroesophageal cancer. In her presentation, she addressed the advantages and disadvantages of EMR and endoscopic submucosal dissection (ESD) for esophageal neoplasia for both diagnosis and treatment.
Esophageal neoplasia therapy includes tissue-acquiring (lesion removal and histopathologic samples) and non–tissue-acquiring therapies (which include radiofrequency ablation, cryotherapy and hybrid-argon plasma coagulation.
The optimal therapy may vary with the esophageal cancer, and the cancer may vary with geography. Worldwide, squamous cell carcinoma is predominant, while in Western countries, esophageal adenocarcinoma is most prevalent. The incidence and mortality of esophageal adenocarcinoma has been rising for several decades, Dr. Konda said.
Considering risk factors
Barrett’s esophagus is a known risk factor for esophageal adenocarcinoma. It can be seen endoscopically as salmon-colored lining, and histologically as specialized intestinal metaplasia.
A lesion extending beyond the basement membrane into the lamina propria is an intramucosal carcinoma, or T1a lesion. A lesion extending beyond the muscularis mucosa into the submucosa is a submucosal carcinoma, or T1b tumor, Dr. Konda said.
“The difference between T1a and T1b is important in the selection of treatment approaches due to the risk of [lymph node] metastasis,” she said. She equated a T1a lesion with a 2% or smaller risk of lymph node metastasis, and a T1b tumor with a 20% risk.*
Endoscopic therapy is more reasonable for a T1a lesion, especially since the alternative, esophagectomy, may have a mortality rate of 2% or higher, she said, while for T1b tumors, surgical or systemic treatments are warranted.
A diagnosis of high-grade dysplasia by biopsy is associated with a 40% risk of prevalent cancer, mostly intramucosal carcinoma. On the other hand, submucosal carcinoma is rare in the absence of endoscopically visible lesions. “This risk of prevalent cancer, especially in visible lesions, is the reason that we should address all visible lesions with endoscopic resection, especially in the setting of dysplasia,” Dr. Konda said.
EMR is more accurate than biopsies; diagnoses change up to half the time when EMR is done after a preresection biopsy, and there’s a higher interobserver agreement among pathologists with EMR, she said.
The goal of therapy in Barrett’s esophagus is total Barrett’s eradication to treat not only the known neoplasia, but also the rest of the at-risk epithelium.
Piecemeal EMR for the entire Barrett’s epithelium can bring about a 96% or greater neoplasia eradication rate. But the stricture rate may reach 37%, and bleeding and perforation are also common.
Combining endoscopic mucosal resection for visible lesions with ablation for the rest of the at-risk lining can achieve an eradication rate of 93% with a more favorable complication profile.
Weighing the benefits of ESD
In contrast to EMR, ESD has been practiced more frequently in Asia. It provides an en bloc specimen.
A 2014 systematic review of 380 EMR procedures and 333 ESD procedures for Barret’s associated neoplasia indicated that ESD takes longer. The recurrence rate was 0.7% for ESD versus 2.6% for EMR, but this difference fell just short of statistical significance (P = .06). Bleeding and perforation rates were similar, but stricture rates reached 22.3% with wide-field EMR, 3.4% with ESD and 0.7% with focal EMR.
In a 2016 head-to-head trial, researchers assigned 20 patients each to EMR or ESD. They found the procedure longer, but the en bloc resection was higher in ESD. Complete remission of the neoplasia was not statistically different between the two groups, with 15 of 16 patients achieving this goal with ESD and 16 of 17 with EMR. All the patients had complete remission after one retreatment of residual neoplasia. There were two severe adverse events in the ESD group, and none in the EMR group.
Weighing the pros and cons, Dr. Konda concluded that EMR is technically easier and adequate in most cases of Barrett’s esophagus, while ESD may be preferred in select cases with concern for submucosal carcinoma or nonlifting lesions.
She advocated taking patient characteristics, disease characteristics, and available expertise into account.
Dr. Konda reported financial relationships with Ambu, Cernostics, Exact Sciences, Medtronic, and Lucid Sciences. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
*Correction, 1/28/22: An earlier version of this article mischaracterized lymph node metastasis.
FROM GI CANCERS SYMPOSIUM 2022
Decades of research fail to resolve disparities in gastrointestinal cancer care
Men and White people receive better treatment for gastroesophageal cancer than women, Blacks, and Latinos despite years of studies highlighting disparities in care, researchers say.
The problem is complex because it stems from both biological and socioeconomic factors, but some signs of improvement are beginning to show, said Nathaniel R. Evans III, MD, a professor of surgery at Thomas Jefferson University in Philadelphia.
“Repeatedly, we see that, although we know how patients should be treated, there are oftentimes subsets of patients who don’t receive that same level of care,” said Dr. Evans in a general session talk at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
Black patients with esophageal cancer are 38% more likely to die from the condition than White patients, he said, citing a 2013 study (Ann Surg Oncol. 2013 doi: 10.1245/s10434-012-2807-3). For Latino patients, mortality is 20% higher than for White patients.
The difference can mostly be explained by the rate of esophagectomy, which is 52% lower for Black patients and 29% lower for Latino patients, compared with White patients, the study found.
Besides race and gender, insurance status also influences who gets surgery, Dr. Evans said, citing data from the National Cancer Database. Black patients are less likely to get surgery and more likely to die at all stages and histologies, he said. They wait longer for treatment and are more likely to receive no treatment at all.
Women also suffer from disparities, said Anna Dorothea Wagner, MD, head of the gastrointestinal cancer clinic at Lausanne University Hospital in Lausanne (Switzerland), who spoke at the symposium with Dr Evans.
Seventy-five percent of men with esophageal and gastric adenocarcinoma get curative treatments, compared with only 60% of women, Dr. Wagner said, citing a 2020 study on which she is an author. Women are more likely to get palliative care. As a result, only 30% of women survive the condition for 5 years or more compared to 34% of men, she said. “At the moment we don’t know whether this is due to either patient preferences or cognitive or bias of physicians.”
Disparities in treatment outcomes because of biological differences
For women, some disparities also arise out of clear biological differences, Dr. Wagner said. Sex hormone signaling affects cancer susceptibility, and sex-biased gene expression signatures have been detected in multiple cancer types.
Women with poorly differentiated and signet-cell pathology are less likely to survive their cancer than men with the same histology, she said.
Many studies have shown that chemotherapy is more toxic to women than men without being more efficacious, she added. This suggests that the optimal doses might be different for women and men.
Responding to a question from the audience, Dr. Wagner said more research is needed on transgender patients to understand how these factors affect them.
Dr. Evans attributed the racial and ethnic disparities to some combination of differential histology, stage at diagnosis, access to care, socioeconomics, and inherent bias.
“The problem is not new,” Dr. Evans said. He described studies that found disparities in the 1970s. “But the good news is that things do seem to be getting better.”
Between 2000 and 2011, the number of esophagectomies being performed at high-volume hospitals increased, he said. The overall mortality after esophagectomy has consequently decreased over this time, and the gap in this rate between White and Black people has closed, he said. “Specialization and centralization clearly improve outcomes for certain surgical procedures.”
To address the problem everyone should acknowledge the disparities, particularly in the access to surgery. “I think one of the best tools we have to try to address the disparity is education, both for patients and providers,” Dr. Evans said.
Care teams must become more diverse and culturally competent to combat longstanding distrust and improve communication, he said.
In December, ASCO announced an “action plan” to address equity, diversity and inclusion in cancer care. The organization promised to improve clinical trial eligibility, and train researchers about inherent bias in order to make the trials more representative of the cancer population.
It vowed to increase participation of underrepresented groups in its professional development programs and leadership roles, and educate its members about equity. And, it resolved to provide resources to providers so they could advocate for better quality of care, especially in rural and disadvantaged settings.
Dr. Wagner disclosed relationships with Alligator Bioscience, BMS, Dragonfly Therapeutics, Lilly, Merck KGaA, MSD Oncology, Servier/Pfizer, and Abbvie. Dr. Evans disclosed relationships with Bristol Myers Squibb Foundation and Intuitive Surgical.
This article was updated 1/28/22.
Men and White people receive better treatment for gastroesophageal cancer than women, Blacks, and Latinos despite years of studies highlighting disparities in care, researchers say.
The problem is complex because it stems from both biological and socioeconomic factors, but some signs of improvement are beginning to show, said Nathaniel R. Evans III, MD, a professor of surgery at Thomas Jefferson University in Philadelphia.
“Repeatedly, we see that, although we know how patients should be treated, there are oftentimes subsets of patients who don’t receive that same level of care,” said Dr. Evans in a general session talk at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
Black patients with esophageal cancer are 38% more likely to die from the condition than White patients, he said, citing a 2013 study (Ann Surg Oncol. 2013 doi: 10.1245/s10434-012-2807-3). For Latino patients, mortality is 20% higher than for White patients.
The difference can mostly be explained by the rate of esophagectomy, which is 52% lower for Black patients and 29% lower for Latino patients, compared with White patients, the study found.
Besides race and gender, insurance status also influences who gets surgery, Dr. Evans said, citing data from the National Cancer Database. Black patients are less likely to get surgery and more likely to die at all stages and histologies, he said. They wait longer for treatment and are more likely to receive no treatment at all.
Women also suffer from disparities, said Anna Dorothea Wagner, MD, head of the gastrointestinal cancer clinic at Lausanne University Hospital in Lausanne (Switzerland), who spoke at the symposium with Dr Evans.
Seventy-five percent of men with esophageal and gastric adenocarcinoma get curative treatments, compared with only 60% of women, Dr. Wagner said, citing a 2020 study on which she is an author. Women are more likely to get palliative care. As a result, only 30% of women survive the condition for 5 years or more compared to 34% of men, she said. “At the moment we don’t know whether this is due to either patient preferences or cognitive or bias of physicians.”
Disparities in treatment outcomes because of biological differences
For women, some disparities also arise out of clear biological differences, Dr. Wagner said. Sex hormone signaling affects cancer susceptibility, and sex-biased gene expression signatures have been detected in multiple cancer types.
Women with poorly differentiated and signet-cell pathology are less likely to survive their cancer than men with the same histology, she said.
Many studies have shown that chemotherapy is more toxic to women than men without being more efficacious, she added. This suggests that the optimal doses might be different for women and men.
Responding to a question from the audience, Dr. Wagner said more research is needed on transgender patients to understand how these factors affect them.
Dr. Evans attributed the racial and ethnic disparities to some combination of differential histology, stage at diagnosis, access to care, socioeconomics, and inherent bias.
“The problem is not new,” Dr. Evans said. He described studies that found disparities in the 1970s. “But the good news is that things do seem to be getting better.”
Between 2000 and 2011, the number of esophagectomies being performed at high-volume hospitals increased, he said. The overall mortality after esophagectomy has consequently decreased over this time, and the gap in this rate between White and Black people has closed, he said. “Specialization and centralization clearly improve outcomes for certain surgical procedures.”
To address the problem everyone should acknowledge the disparities, particularly in the access to surgery. “I think one of the best tools we have to try to address the disparity is education, both for patients and providers,” Dr. Evans said.
Care teams must become more diverse and culturally competent to combat longstanding distrust and improve communication, he said.
In December, ASCO announced an “action plan” to address equity, diversity and inclusion in cancer care. The organization promised to improve clinical trial eligibility, and train researchers about inherent bias in order to make the trials more representative of the cancer population.
It vowed to increase participation of underrepresented groups in its professional development programs and leadership roles, and educate its members about equity. And, it resolved to provide resources to providers so they could advocate for better quality of care, especially in rural and disadvantaged settings.
Dr. Wagner disclosed relationships with Alligator Bioscience, BMS, Dragonfly Therapeutics, Lilly, Merck KGaA, MSD Oncology, Servier/Pfizer, and Abbvie. Dr. Evans disclosed relationships with Bristol Myers Squibb Foundation and Intuitive Surgical.
This article was updated 1/28/22.
Men and White people receive better treatment for gastroesophageal cancer than women, Blacks, and Latinos despite years of studies highlighting disparities in care, researchers say.
The problem is complex because it stems from both biological and socioeconomic factors, but some signs of improvement are beginning to show, said Nathaniel R. Evans III, MD, a professor of surgery at Thomas Jefferson University in Philadelphia.
“Repeatedly, we see that, although we know how patients should be treated, there are oftentimes subsets of patients who don’t receive that same level of care,” said Dr. Evans in a general session talk at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
Black patients with esophageal cancer are 38% more likely to die from the condition than White patients, he said, citing a 2013 study (Ann Surg Oncol. 2013 doi: 10.1245/s10434-012-2807-3). For Latino patients, mortality is 20% higher than for White patients.
The difference can mostly be explained by the rate of esophagectomy, which is 52% lower for Black patients and 29% lower for Latino patients, compared with White patients, the study found.
Besides race and gender, insurance status also influences who gets surgery, Dr. Evans said, citing data from the National Cancer Database. Black patients are less likely to get surgery and more likely to die at all stages and histologies, he said. They wait longer for treatment and are more likely to receive no treatment at all.
Women also suffer from disparities, said Anna Dorothea Wagner, MD, head of the gastrointestinal cancer clinic at Lausanne University Hospital in Lausanne (Switzerland), who spoke at the symposium with Dr Evans.
Seventy-five percent of men with esophageal and gastric adenocarcinoma get curative treatments, compared with only 60% of women, Dr. Wagner said, citing a 2020 study on which she is an author. Women are more likely to get palliative care. As a result, only 30% of women survive the condition for 5 years or more compared to 34% of men, she said. “At the moment we don’t know whether this is due to either patient preferences or cognitive or bias of physicians.”
Disparities in treatment outcomes because of biological differences
For women, some disparities also arise out of clear biological differences, Dr. Wagner said. Sex hormone signaling affects cancer susceptibility, and sex-biased gene expression signatures have been detected in multiple cancer types.
Women with poorly differentiated and signet-cell pathology are less likely to survive their cancer than men with the same histology, she said.
Many studies have shown that chemotherapy is more toxic to women than men without being more efficacious, she added. This suggests that the optimal doses might be different for women and men.
Responding to a question from the audience, Dr. Wagner said more research is needed on transgender patients to understand how these factors affect them.
Dr. Evans attributed the racial and ethnic disparities to some combination of differential histology, stage at diagnosis, access to care, socioeconomics, and inherent bias.
“The problem is not new,” Dr. Evans said. He described studies that found disparities in the 1970s. “But the good news is that things do seem to be getting better.”
Between 2000 and 2011, the number of esophagectomies being performed at high-volume hospitals increased, he said. The overall mortality after esophagectomy has consequently decreased over this time, and the gap in this rate between White and Black people has closed, he said. “Specialization and centralization clearly improve outcomes for certain surgical procedures.”
To address the problem everyone should acknowledge the disparities, particularly in the access to surgery. “I think one of the best tools we have to try to address the disparity is education, both for patients and providers,” Dr. Evans said.
Care teams must become more diverse and culturally competent to combat longstanding distrust and improve communication, he said.
In December, ASCO announced an “action plan” to address equity, diversity and inclusion in cancer care. The organization promised to improve clinical trial eligibility, and train researchers about inherent bias in order to make the trials more representative of the cancer population.
It vowed to increase participation of underrepresented groups in its professional development programs and leadership roles, and educate its members about equity. And, it resolved to provide resources to providers so they could advocate for better quality of care, especially in rural and disadvantaged settings.
Dr. Wagner disclosed relationships with Alligator Bioscience, BMS, Dragonfly Therapeutics, Lilly, Merck KGaA, MSD Oncology, Servier/Pfizer, and Abbvie. Dr. Evans disclosed relationships with Bristol Myers Squibb Foundation and Intuitive Surgical.
This article was updated 1/28/22.
FROM GI CANCERS SYMPOSIUM 2022
Can immunotherapy replace surgery for stomach cancer?
GERCOR NEONIPIGA was a phase 2 study with no comparator group and only 32 patients, but even so, after a 6-cycle course of nivolumab and ipilimumab, there was no sign of tumor in 17 of the 29 patients (59%) who had surgery specimens evaluable by pathology.
Indeed, two patients refused surgery after their preop endoscopic biopsies came back clear with no tumor cells. Surgery was called off in a third patient who developed metastases beforehand.
After a median of 12 months follow-up, there’s was no recurrence or progression in 30 patients (94%). The remaining two included the metastatic patient and one who died 3 days after surgery from cardiovascular complications.
If the findings pan out with additional research, the approach could be a boon for people who respond. “Avoiding surgery is a dream for these patients,” said lead investigator Thierry Andre, MD, a medical oncology professor at Sorbonne University, Paris, when he presented the findings at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
The trial “raises the question whether surgery can be delayed or avoided in some patients with localized” disease. Given the findings, “it seems possible not for all but probably for half, maybe more.” As in the two subjects who opted out of surgery, preop endoscopic biopsies could be used to identify complete responders with active surveillance afterwards, he said.
The study included 16 patients with gastric cancer and 16 with esophagogastric adenocarcinoma. They were mismatch repair deficient, which Dr. Andre said predicts response to immunotherapy.
At baseline, 22 had stage T3 disease and four had stage T2 disease, and stage was not evaluable by echo-endoscopy in 6. Nodal status was unknown, but the patients had no metastases at baseline.
They underwent six nivolumab 240-mg infusions and two ipilimumab 1–mg/kg infusions over 12 weeks, followed by R0 resections a median of 5 weeks after the last nivolumab injection.
Surgical specimens from 17 patients (59%) showed a complete pathological response to neoadjuvant immunotherapy (Becker tumor regression grade (TRG) 1a, ypT0N0). TRG was 1b – less than 10% residual tumor in tumor bed in four patients. TRG was 2 in two patients with 10%-50% of residual tumor remaining, and six had a TRG of 3 with more than half of the tumor remaining after immunotherapy.
Based on tumor response, 25 patients had nine additional nivolumab infusions after surgery with 480 mg infused monthly.
Dr. Andre explained that people want to avoid surgery because of the substantial morbidity that was shown in the study, plus 54% of patients had complications, including anastomotic leaks, pancreatitis, pneumonia, and other problems.
There were no new safety signals with neoadjuvant therapy; 25% of patients had grade 3 or 4 events.
The study was conducted in 10 centers in France. About three-quarters of the subjects were men and the median age was 65 years.
Bristol Meyers Squibb supplied the nivolumab and ipilimumab and partially funded the work. Many of the investigators had ties to the company, including Dr. Andre, who is a consultant for BMS and reported payments from the company.
GERCOR NEONIPIGA was a phase 2 study with no comparator group and only 32 patients, but even so, after a 6-cycle course of nivolumab and ipilimumab, there was no sign of tumor in 17 of the 29 patients (59%) who had surgery specimens evaluable by pathology.
Indeed, two patients refused surgery after their preop endoscopic biopsies came back clear with no tumor cells. Surgery was called off in a third patient who developed metastases beforehand.
After a median of 12 months follow-up, there’s was no recurrence or progression in 30 patients (94%). The remaining two included the metastatic patient and one who died 3 days after surgery from cardiovascular complications.
If the findings pan out with additional research, the approach could be a boon for people who respond. “Avoiding surgery is a dream for these patients,” said lead investigator Thierry Andre, MD, a medical oncology professor at Sorbonne University, Paris, when he presented the findings at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
The trial “raises the question whether surgery can be delayed or avoided in some patients with localized” disease. Given the findings, “it seems possible not for all but probably for half, maybe more.” As in the two subjects who opted out of surgery, preop endoscopic biopsies could be used to identify complete responders with active surveillance afterwards, he said.
The study included 16 patients with gastric cancer and 16 with esophagogastric adenocarcinoma. They were mismatch repair deficient, which Dr. Andre said predicts response to immunotherapy.
At baseline, 22 had stage T3 disease and four had stage T2 disease, and stage was not evaluable by echo-endoscopy in 6. Nodal status was unknown, but the patients had no metastases at baseline.
They underwent six nivolumab 240-mg infusions and two ipilimumab 1–mg/kg infusions over 12 weeks, followed by R0 resections a median of 5 weeks after the last nivolumab injection.
Surgical specimens from 17 patients (59%) showed a complete pathological response to neoadjuvant immunotherapy (Becker tumor regression grade (TRG) 1a, ypT0N0). TRG was 1b – less than 10% residual tumor in tumor bed in four patients. TRG was 2 in two patients with 10%-50% of residual tumor remaining, and six had a TRG of 3 with more than half of the tumor remaining after immunotherapy.
Based on tumor response, 25 patients had nine additional nivolumab infusions after surgery with 480 mg infused monthly.
Dr. Andre explained that people want to avoid surgery because of the substantial morbidity that was shown in the study, plus 54% of patients had complications, including anastomotic leaks, pancreatitis, pneumonia, and other problems.
There were no new safety signals with neoadjuvant therapy; 25% of patients had grade 3 or 4 events.
The study was conducted in 10 centers in France. About three-quarters of the subjects were men and the median age was 65 years.
Bristol Meyers Squibb supplied the nivolumab and ipilimumab and partially funded the work. Many of the investigators had ties to the company, including Dr. Andre, who is a consultant for BMS and reported payments from the company.
GERCOR NEONIPIGA was a phase 2 study with no comparator group and only 32 patients, but even so, after a 6-cycle course of nivolumab and ipilimumab, there was no sign of tumor in 17 of the 29 patients (59%) who had surgery specimens evaluable by pathology.
Indeed, two patients refused surgery after their preop endoscopic biopsies came back clear with no tumor cells. Surgery was called off in a third patient who developed metastases beforehand.
After a median of 12 months follow-up, there’s was no recurrence or progression in 30 patients (94%). The remaining two included the metastatic patient and one who died 3 days after surgery from cardiovascular complications.
If the findings pan out with additional research, the approach could be a boon for people who respond. “Avoiding surgery is a dream for these patients,” said lead investigator Thierry Andre, MD, a medical oncology professor at Sorbonne University, Paris, when he presented the findings at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
The trial “raises the question whether surgery can be delayed or avoided in some patients with localized” disease. Given the findings, “it seems possible not for all but probably for half, maybe more.” As in the two subjects who opted out of surgery, preop endoscopic biopsies could be used to identify complete responders with active surveillance afterwards, he said.
The study included 16 patients with gastric cancer and 16 with esophagogastric adenocarcinoma. They were mismatch repair deficient, which Dr. Andre said predicts response to immunotherapy.
At baseline, 22 had stage T3 disease and four had stage T2 disease, and stage was not evaluable by echo-endoscopy in 6. Nodal status was unknown, but the patients had no metastases at baseline.
They underwent six nivolumab 240-mg infusions and two ipilimumab 1–mg/kg infusions over 12 weeks, followed by R0 resections a median of 5 weeks after the last nivolumab injection.
Surgical specimens from 17 patients (59%) showed a complete pathological response to neoadjuvant immunotherapy (Becker tumor regression grade (TRG) 1a, ypT0N0). TRG was 1b – less than 10% residual tumor in tumor bed in four patients. TRG was 2 in two patients with 10%-50% of residual tumor remaining, and six had a TRG of 3 with more than half of the tumor remaining after immunotherapy.
Based on tumor response, 25 patients had nine additional nivolumab infusions after surgery with 480 mg infused monthly.
Dr. Andre explained that people want to avoid surgery because of the substantial morbidity that was shown in the study, plus 54% of patients had complications, including anastomotic leaks, pancreatitis, pneumonia, and other problems.
There were no new safety signals with neoadjuvant therapy; 25% of patients had grade 3 or 4 events.
The study was conducted in 10 centers in France. About three-quarters of the subjects were men and the median age was 65 years.
Bristol Meyers Squibb supplied the nivolumab and ipilimumab and partially funded the work. Many of the investigators had ties to the company, including Dr. Andre, who is a consultant for BMS and reported payments from the company.
FROM GI CANCERS SYMPOSIUM 2022
Oxaliplatin add-on not recommended for elderly with colon cancer
A Japanese study finds that the addition of oxaliplatin (Eloxatin, Sanofi-Aventis) to fluoropyrimidine with bevacizumab, does not extend progression-free survival in elderly patients with metastatic colorectal cancer and in fact, can lead to more severe adverse events.
The results of the trial were presented by Tetsuya Hamaguchi, MD, PhD, at the 2022 Gastrointestinal Cancers Symposium.
Fluoropyrimidine with oxaliplatin and bevacizumab is a standard intensive initial therapy for metastatic colorectal cancer, but how well this combination works in elderly patients isn’t known because few clinical trials include senior-aged patients. It is known that the combination of fluoropyrimidine and bevacizumab can lead to significantly longer progression-free survival in elderly patients with metastatic colorectal cancer.
Dr. Hamaguchi, an oncologist with Saitama Medical University International Medical Center in Hidaka, Japan, included 251 patients (93% were at least 75 years old) with newly diagnosed metastatic colorectal cancer in a randomized, phase 3 trial of modified FOLFOX7 (folinic acid, fluorouracil, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) plus bevacizumab versus 5-fluorouracil/l-LV or capecitabine plus bevacizumab.
The patients were treated between September 2012 and March 2019. 125 patients received combination therapy and 126 received the addition of oxaliplatin. Researchers found the addition of oxaliplatin to fluoropyrimidine with bevacizumab did not extend progression-free survival and it was associated with more frequent and severe adverse events, including neutropenia, nausea, stomatitis, diarrhea, fatigue, sensory neuropathy, and hypertension.
Triggering sensory neuropathy
At issue is neuropathy caused by oxaliplatin. Grade 3 neuropathy can occur in 25% of patients after 12 cycles of FOLFOX. It has also been recorded in more than 20% of patients at 18 months, according to Gabriel Brooks, MD, an oncologist with the Dartmouth-Hitchcock Norris Cotton Cancer Center, Lebanon, N.H., who served as the discussant for the oral abstract session featuring the study presented by Dr. Hamaguchi.
“Even if we carefully ask our patients about their symptoms, and even if we stop oxaliplatin as soon as they have evidence of grade 2 neuropathy, many of those patients who didn’t have any neuropathy when the oxaliplatin is stopped will go on to develop it. And many of those patients who have grade 2 neuropathy will have worsening of their neuropathy and it will become a grade 3 neuropathy, even if we try to stop conscientiously,” Dr. Brooks said during his presentation.
The MOSAIC trial demonstrated that oxaliplatin improved disease-free and overall survival when added to 5-fluorouracil in the adjuvant treatment of stage II/III colon cancer. However, neuropathy concerns led to studies examining shortened regimens in an effort to reduce neuropathy incidence. In 2018, the IDEA study compared 3 months versus 6 months of oxaliplatin with fluoropyrimidine as adjuvant therapy for stage III colon cancer. The study found that the 6-month regimen was superior with respect to disease-free survival, but the benefit was very small, according to Dr. Brooks.
“What was not small was the difference in the incidence of [grade] 3-4 neuropathy, which was only 2.5% among patients who received 3 months of adjuvant chemotherapy with oxaliplatin, and it was 15.9% among people randomized to 6 months of adjuvant chemotherapy,” he said. The same study suggested that 3 months of the CapeOX regimen is noninferior to 6 months.
The new study included patients aged 70-74 years with Performance Status 2, or 75 or older with PS 0-2. They were randomized to receive fluoropyrimidine plus bevacizumab (arm A) or fluoropyrimidine, bevacizumab, and oxaliplatin (arm B). The study had to be terminated because of poor accrual, and the study was later amended to include a smaller required sample size. After a recruitment of 251 patients and a 2-year minimum follow-up, there was no significant difference in progression-free survival between the two groups (hazard ratio, 0.837; one-sided P = .086), overall survival, or objective response rate.
Adverse events were more common in the oxaliplatin group, including neutropenia (24% vs. 15%), nausea (22% vs. 10%), diarrhea (16% vs. 7%), fatigue (32% vs. 21%), and sensory neuropathy (57% vs. 15%).
Subgroup analyses did identify a subgroup of patients with KRAS wild type benefited from oxaliplatin (HR, 0.578; 95% confidence interval, 0.380-0.879), and Dr. Brooks said that this echoes findings from other studies.
Dr. Brooks advocated for deintensification of oxaliplatin. “The benefits of oxaliplatin are less than are often assumed in multiple settings, and the harms of oxaliplatin are well described. We are probably overly aggressive in our use of oxaliplatin. I submit that we should use oxaliplatin cautiously and sparingly in a couple of situations: We should use it very cautiously and sparingly beyond the third month of adjuvant therapy for colon cancer, and we should use it cautiously and sparingly in elderly or frail patients with metastatic colorectal cancer.”
The study was funded, in part, by the National Cancer Center Research and Development Fund, Grant-in-Aid for Clinical Cancer Research, and the Agency for Medical Research and Development in Japan. Dr. Brooks has consulted for CareCentrix, Ipsen, and UnitedHealthcare and has received research funding from Boston Biomedical and Roche/Genentech. Dr. Hamaguchi has received honoraria from Bayer, Bristol-Myers Squibb Japan, and other pharmaceutical companies. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
A Japanese study finds that the addition of oxaliplatin (Eloxatin, Sanofi-Aventis) to fluoropyrimidine with bevacizumab, does not extend progression-free survival in elderly patients with metastatic colorectal cancer and in fact, can lead to more severe adverse events.
The results of the trial were presented by Tetsuya Hamaguchi, MD, PhD, at the 2022 Gastrointestinal Cancers Symposium.
Fluoropyrimidine with oxaliplatin and bevacizumab is a standard intensive initial therapy for metastatic colorectal cancer, but how well this combination works in elderly patients isn’t known because few clinical trials include senior-aged patients. It is known that the combination of fluoropyrimidine and bevacizumab can lead to significantly longer progression-free survival in elderly patients with metastatic colorectal cancer.
Dr. Hamaguchi, an oncologist with Saitama Medical University International Medical Center in Hidaka, Japan, included 251 patients (93% were at least 75 years old) with newly diagnosed metastatic colorectal cancer in a randomized, phase 3 trial of modified FOLFOX7 (folinic acid, fluorouracil, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) plus bevacizumab versus 5-fluorouracil/l-LV or capecitabine plus bevacizumab.
The patients were treated between September 2012 and March 2019. 125 patients received combination therapy and 126 received the addition of oxaliplatin. Researchers found the addition of oxaliplatin to fluoropyrimidine with bevacizumab did not extend progression-free survival and it was associated with more frequent and severe adverse events, including neutropenia, nausea, stomatitis, diarrhea, fatigue, sensory neuropathy, and hypertension.
Triggering sensory neuropathy
At issue is neuropathy caused by oxaliplatin. Grade 3 neuropathy can occur in 25% of patients after 12 cycles of FOLFOX. It has also been recorded in more than 20% of patients at 18 months, according to Gabriel Brooks, MD, an oncologist with the Dartmouth-Hitchcock Norris Cotton Cancer Center, Lebanon, N.H., who served as the discussant for the oral abstract session featuring the study presented by Dr. Hamaguchi.
“Even if we carefully ask our patients about their symptoms, and even if we stop oxaliplatin as soon as they have evidence of grade 2 neuropathy, many of those patients who didn’t have any neuropathy when the oxaliplatin is stopped will go on to develop it. And many of those patients who have grade 2 neuropathy will have worsening of their neuropathy and it will become a grade 3 neuropathy, even if we try to stop conscientiously,” Dr. Brooks said during his presentation.
The MOSAIC trial demonstrated that oxaliplatin improved disease-free and overall survival when added to 5-fluorouracil in the adjuvant treatment of stage II/III colon cancer. However, neuropathy concerns led to studies examining shortened regimens in an effort to reduce neuropathy incidence. In 2018, the IDEA study compared 3 months versus 6 months of oxaliplatin with fluoropyrimidine as adjuvant therapy for stage III colon cancer. The study found that the 6-month regimen was superior with respect to disease-free survival, but the benefit was very small, according to Dr. Brooks.
“What was not small was the difference in the incidence of [grade] 3-4 neuropathy, which was only 2.5% among patients who received 3 months of adjuvant chemotherapy with oxaliplatin, and it was 15.9% among people randomized to 6 months of adjuvant chemotherapy,” he said. The same study suggested that 3 months of the CapeOX regimen is noninferior to 6 months.
The new study included patients aged 70-74 years with Performance Status 2, or 75 or older with PS 0-2. They were randomized to receive fluoropyrimidine plus bevacizumab (arm A) or fluoropyrimidine, bevacizumab, and oxaliplatin (arm B). The study had to be terminated because of poor accrual, and the study was later amended to include a smaller required sample size. After a recruitment of 251 patients and a 2-year minimum follow-up, there was no significant difference in progression-free survival between the two groups (hazard ratio, 0.837; one-sided P = .086), overall survival, or objective response rate.
Adverse events were more common in the oxaliplatin group, including neutropenia (24% vs. 15%), nausea (22% vs. 10%), diarrhea (16% vs. 7%), fatigue (32% vs. 21%), and sensory neuropathy (57% vs. 15%).
Subgroup analyses did identify a subgroup of patients with KRAS wild type benefited from oxaliplatin (HR, 0.578; 95% confidence interval, 0.380-0.879), and Dr. Brooks said that this echoes findings from other studies.
Dr. Brooks advocated for deintensification of oxaliplatin. “The benefits of oxaliplatin are less than are often assumed in multiple settings, and the harms of oxaliplatin are well described. We are probably overly aggressive in our use of oxaliplatin. I submit that we should use oxaliplatin cautiously and sparingly in a couple of situations: We should use it very cautiously and sparingly beyond the third month of adjuvant therapy for colon cancer, and we should use it cautiously and sparingly in elderly or frail patients with metastatic colorectal cancer.”
The study was funded, in part, by the National Cancer Center Research and Development Fund, Grant-in-Aid for Clinical Cancer Research, and the Agency for Medical Research and Development in Japan. Dr. Brooks has consulted for CareCentrix, Ipsen, and UnitedHealthcare and has received research funding from Boston Biomedical and Roche/Genentech. Dr. Hamaguchi has received honoraria from Bayer, Bristol-Myers Squibb Japan, and other pharmaceutical companies. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
A Japanese study finds that the addition of oxaliplatin (Eloxatin, Sanofi-Aventis) to fluoropyrimidine with bevacizumab, does not extend progression-free survival in elderly patients with metastatic colorectal cancer and in fact, can lead to more severe adverse events.
The results of the trial were presented by Tetsuya Hamaguchi, MD, PhD, at the 2022 Gastrointestinal Cancers Symposium.
Fluoropyrimidine with oxaliplatin and bevacizumab is a standard intensive initial therapy for metastatic colorectal cancer, but how well this combination works in elderly patients isn’t known because few clinical trials include senior-aged patients. It is known that the combination of fluoropyrimidine and bevacizumab can lead to significantly longer progression-free survival in elderly patients with metastatic colorectal cancer.
Dr. Hamaguchi, an oncologist with Saitama Medical University International Medical Center in Hidaka, Japan, included 251 patients (93% were at least 75 years old) with newly diagnosed metastatic colorectal cancer in a randomized, phase 3 trial of modified FOLFOX7 (folinic acid, fluorouracil, and oxaliplatin) or CapeOX (capecitabine and oxaliplatin) plus bevacizumab versus 5-fluorouracil/l-LV or capecitabine plus bevacizumab.
The patients were treated between September 2012 and March 2019. 125 patients received combination therapy and 126 received the addition of oxaliplatin. Researchers found the addition of oxaliplatin to fluoropyrimidine with bevacizumab did not extend progression-free survival and it was associated with more frequent and severe adverse events, including neutropenia, nausea, stomatitis, diarrhea, fatigue, sensory neuropathy, and hypertension.
Triggering sensory neuropathy
At issue is neuropathy caused by oxaliplatin. Grade 3 neuropathy can occur in 25% of patients after 12 cycles of FOLFOX. It has also been recorded in more than 20% of patients at 18 months, according to Gabriel Brooks, MD, an oncologist with the Dartmouth-Hitchcock Norris Cotton Cancer Center, Lebanon, N.H., who served as the discussant for the oral abstract session featuring the study presented by Dr. Hamaguchi.
“Even if we carefully ask our patients about their symptoms, and even if we stop oxaliplatin as soon as they have evidence of grade 2 neuropathy, many of those patients who didn’t have any neuropathy when the oxaliplatin is stopped will go on to develop it. And many of those patients who have grade 2 neuropathy will have worsening of their neuropathy and it will become a grade 3 neuropathy, even if we try to stop conscientiously,” Dr. Brooks said during his presentation.
The MOSAIC trial demonstrated that oxaliplatin improved disease-free and overall survival when added to 5-fluorouracil in the adjuvant treatment of stage II/III colon cancer. However, neuropathy concerns led to studies examining shortened regimens in an effort to reduce neuropathy incidence. In 2018, the IDEA study compared 3 months versus 6 months of oxaliplatin with fluoropyrimidine as adjuvant therapy for stage III colon cancer. The study found that the 6-month regimen was superior with respect to disease-free survival, but the benefit was very small, according to Dr. Brooks.
“What was not small was the difference in the incidence of [grade] 3-4 neuropathy, which was only 2.5% among patients who received 3 months of adjuvant chemotherapy with oxaliplatin, and it was 15.9% among people randomized to 6 months of adjuvant chemotherapy,” he said. The same study suggested that 3 months of the CapeOX regimen is noninferior to 6 months.
The new study included patients aged 70-74 years with Performance Status 2, or 75 or older with PS 0-2. They were randomized to receive fluoropyrimidine plus bevacizumab (arm A) or fluoropyrimidine, bevacizumab, and oxaliplatin (arm B). The study had to be terminated because of poor accrual, and the study was later amended to include a smaller required sample size. After a recruitment of 251 patients and a 2-year minimum follow-up, there was no significant difference in progression-free survival between the two groups (hazard ratio, 0.837; one-sided P = .086), overall survival, or objective response rate.
Adverse events were more common in the oxaliplatin group, including neutropenia (24% vs. 15%), nausea (22% vs. 10%), diarrhea (16% vs. 7%), fatigue (32% vs. 21%), and sensory neuropathy (57% vs. 15%).
Subgroup analyses did identify a subgroup of patients with KRAS wild type benefited from oxaliplatin (HR, 0.578; 95% confidence interval, 0.380-0.879), and Dr. Brooks said that this echoes findings from other studies.
Dr. Brooks advocated for deintensification of oxaliplatin. “The benefits of oxaliplatin are less than are often assumed in multiple settings, and the harms of oxaliplatin are well described. We are probably overly aggressive in our use of oxaliplatin. I submit that we should use oxaliplatin cautiously and sparingly in a couple of situations: We should use it very cautiously and sparingly beyond the third month of adjuvant therapy for colon cancer, and we should use it cautiously and sparingly in elderly or frail patients with metastatic colorectal cancer.”
The study was funded, in part, by the National Cancer Center Research and Development Fund, Grant-in-Aid for Clinical Cancer Research, and the Agency for Medical Research and Development in Japan. Dr. Brooks has consulted for CareCentrix, Ipsen, and UnitedHealthcare and has received research funding from Boston Biomedical and Roche/Genentech. Dr. Hamaguchi has received honoraria from Bayer, Bristol-Myers Squibb Japan, and other pharmaceutical companies. The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
FROM GI CANCERS SYMPOSIUM 2022