Easily adoptable methods to improve outcomes in treatment of gastroesophageal cancers

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July 9th 2021: During the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2021, two scientists from Roswell Park Comprehensive Cancer Center were asked to share new findings on the treatment of gastroesophageal malignancies. The Roswell Park physician-researchers highlighted easily adoptable strategies that may assist other doctors provide treatment that supports improved patient outcomes in their lectures, both of which were presented on July 1.

Sarbajit Mukherjee, MD, MS, Assistant Professor of Oncology at the Department of Medicine, presented findings from a study that found a link between inflammation, cell proliferation, and prognosis in gastroesophageal cancer patients treated with immunotherapy (Abstract SO-5).

“Immune checkpoint inhibitors (ICI) have transformed the landscape of cancer treatment in recent years,” says Dr. Mukherjee, “but only a small percentage of patients react to this therapy.” “As a result, it is critical that we investigate the possibilities further to determine which patients may benefit the most from immunotherapy.”

Obese people respond better to immune checkpoint inhibitor (ICI) medication than nonobese patients, according to previous study by Dr. Mukherjee and colleagues. They hypothesized that obesity causes inflammation, which can be treated with ICI, and that obesity is linked to a superior response to ICI treatment.

To test this theory, the researchers looked at the gene expression profiles of tumours from individuals with metastatic gastroesophageal cancer. Overweight individuals accounted for 61 percent of the study’s participants, with a BMI of 25 or more.

“We discovered that the tumor’s inflammatory condition was connected with outcomes irrespective of obesity,” he says. “The innovation of our work is the utilization of a unique gene-expression profile to evaluate the tumor’s inflammation status, which can be employed as a biomarker for ICI therapy,” says the researcher.

The researchers assessed gene expression using a routine FDA-approved assay, indicating that this method can be widely used. “Such tests can assist identify patients who are likely to respond to immune checkpoint inhibitors and minimize unnecessary harm in others,” says Dr. Mukherjee, who adds that more research is needed to better understand the function of these processes in ICI therapeutic response.

Researchers looked at the prognostic and predictive impact of preoperative chemotherapy sensitivity in gastric adenocarcinoma in another study led by Dr. Mukherjee’s mentee, Lei Deng, MD, Hematology/Oncology Fellow at Roswell Park (Abstract SO-7).

The researchers found 2,952 patients with stomach adenocarcinoma diagnosed between 2006 and 2017 using the National Cancer Database. The findings demonstrated that sensitivity to preoperative chemotherapy is not only linked to survival in these patients, but that sensitivity can also predict postoperative chemotherapy benefit.

The researchers took a novel technique, determining treatment sensitivity based on changes in stage before and after preoperative chemotherapy and surgery. Sensitivity was classified as very sensitive (no residual disease at the time of surgery after treatment), sensitive (lower stage after treatment), or refractory (no residual disease at the time of surgery after treatment) (no stage change or more advanced disease after treatment).

Patients with sensitive illness were found to benefit significantly from postoperative chemotherapy in this trial. Overall survival in sensitive patients improved after postoperative chemotherapy, with a 5-year survival rate of 73.9 percent compared to 65 percent in those who did not receive it. Very sensitive or refractory patients showed no improvement with postoperative chemotherapy.

These data imply that preoperative chemotherapy sensitivity is prognostic and can predict postoperative chemotherapy benefit in this patient population, although further research is needed.

“While this research is still in its early stages, if our findings are confirmed in prospective trials, this strategy could assist better select patients who should get postoperative chemotherapy while avoiding undue toxicity in those who do not,” Dr. Deng says. “The study’s straightforward sensitivity criteria will also allow for rapid clinical adoption.”

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