Two Roswell Park Comprehensive Cancer Center experts were invited to present new insights on treatment of gastroesophageal cancers during the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2021. In their talks, both presented July 1, the Roswell Park physician-researchers highlighted easily adoptable methods that may help other clinicians to provide care supporting improved patient outcomes.
Sarbajit Mukherjee, MD, MS, Assistant Professor of Oncology in the Department of Medicine, shared findings of a study showing a significant association between inflammation, cell proliferation and outcomes in patients with gastroesophageal cancer who received immunotherapy (Abstract SO-5).
“Immune checkpoint inhibitors (ICI) have changed the landscape of cancer treatment in recent years, yet very few patients respond to this therapy,” notes Dr. Mukherjee. “So it is of utmost importance that we pursue the possibilities further to see which patients can benefit most from immunotherapy.”
Earlier research from Dr. Mukherjee and colleagues shows that obese patients respond better to immune checkpoint inhibitor (ICI) therapy, compared to non-obese patients. They hypothesized that obesity leads to inflammation, which can be reversed by ICI, and that obesity is associated with better treatment response to ICI.
To test this hypothesis, the team here examined the gene expression profile of the tumors from metastatic gastroesophageal cancer patients. Overweight patients — with a body-mass index (BMI) of 25 or more — represented 61 percent of the study cohort.
“We found that the inflammation status of the tumor was independently associated with outcomes, regardless of obesity,” he reports. “The novelty of our work lies in the use of a unique gene-expression profile to determine the inflammation status of the tumor, which can be used as a biomarker for ICI therapy.”
The researchers used a standard FDA-approved test to assess gene expression, which suggests that this approach can be adopted broadly. “Such tests can help preselect patients who are likely to respond to immune checkpoint inhibitors and avoid unnecessary toxicity in others,” Dr. Mukherjee says, noting that further study to better understand the role of these mechanisms in response to ICI therapy is needed.
In another study, spearheaded by Dr. Mukherjee’s mentee, Lei Deng, MD, Hematology/Oncology Fellow at Roswell Park, researchers explored the prognostic and predictive role of preoperative chemotherapy sensitivity in gastric adenocarcinoma (Abstract SO-7).
Using the National Cancer Database, the researchers identified 2,952 patients with gastric adenocarcinoma diagnosed between 2006 to 2017. The data revealed that, among these patients, sensitivity to preoperative chemotherapy is not only associated with survival, but also that sensitivity can predict benefit from postoperative chemotherapy.
The team used a novel approach, defining sensitivity to treatment based on stage change before and after preoperative chemotherapy and surgery. Sensitivity was defined as very sensitive (no residual disease at time of surgery after treatment), sensitive (lower stage after treatment) or refractory (no stage change or more advanced disease after treatment).
In this study, patients with sensitive disease were shown to have a significant survival benefit from postoperative chemotherapy. Postoperative chemotherapy improved overall survival in sensitive patients with a 5-year survival rate of 73.9% compared to 65% among those who did not receive this treatment. No improvement with postoperative chemotherapy was observed among very sensitive or refractory patients.
These findings suggest that sensitivity to preoperative chemotherapy is prognostic and can predict benefit from postoperative chemotherapy in this patient population, but validation is required.
“While this work is at an early stage, if our findings are validated in prospective studies, this approach may help better select patients who should receive postoperative chemotherapy and avoid unnecessary toxicity in those who do not need these treatments,” notes Dr. Deng. “The simple sensitivity definition utilized in this study will also enable rapid clinical adoption.”