Pre-Op Chemosensitivity Tied to Post-Op Survival in Patients With Gastric Tumors

By Lorraine L. Janeczko

December 08, 2021

NEW YORK (Reuters Health) - How long patients with resected gastric adenocarcinoma survive is tied to their preoperative sensitivity to chemotherapy, researchers report.

"Interestingly, in patients with sensitive tumors, there was a significant survival advantage for those who received postoperative chemotherapy," said Dr. Afsaneh Barzi, an associate professor in the Department of Medical Oncology & Therapeutics Research at City of Hope Comprehensive Cancer Center in Duarte, California.

"Sensitive tumors required a cumulatively higher dose of chemotherapy and thus achieved a survival benefit from postoperative chemotherapy," Dr. Barzi, who was not involved in the study, told Reuters Health by email.

As reported in JAMA Open Network, Dr. Lei Deng of Roswell Park Comprehensive Cancer Center in Buffalo, New York, conducted a national, hospital-based cohort study based on 12 years' worth of data from the National Cancer Database. They studied patients with clinical stage-II or -III disease treated with preoperative chemotherapy and curative-intent resection, excluding radiotherapy.

Preoperative chemosensitivity was categorized as very sensitive (ypT0N0), sensitive (pathological TNM stage less than clinical, excluding ypT0N0), and refractory (pathological TNM stage greater than or equal to clinical).

The median age of the 2,382 patients in the study was 63 years, 67% were men, and 64% received no postoperative chemotherapy (PC). Overall, 62% of patients had refractory disease, 31% had sensitive disease, and 7% had very sensitive disease.

Some patients were significantly less likely to receive PC, including those who had comorbidities (odds ratio, 0.71), were less sensitive to PC (very sensitive vs. refractory: OR, 0.58), or had longer surgical hospitalization (OR, 0.95).

Patients with refractory disease had significantly shorter survival compared with patients with sensitive disease (hazard ratio, 0.39) or very sensitive disease (HR, 0.12).

Overall, PC was not significantly associated with improved survival (hazard ratio, 0.88). However, preoperative chemosensitivity was significantly linked with survival benefit from PC (P for interaction = 0.03).

PC was significantly associated with longer survival in patients with sensitive disease (five-year survival, 73.8% in the PC group vs. 65.0% in the no PC group; HR, 0.64), but not in those with very sensitive disease (five-year survival, 80.0% in the PC group vs. 90.8% in the no PC group; HR, 2.45) or those with refractory disease (five-year survival, 41.8% in the PC group vs. 40.7% in the no PC group; HR, 0.93).

Dr. Bassam Estfan, a hematologist and medical oncologist at Cleveland Clinic in Ohio, explained by email, "The conventional management of non-metastatic gastric cancer usually involves administration of perioperative chemotherapy. Prior to 2017, the ECF regimen (epirubicin, cisplatin, and fluorouracil) was widely used, after which the FLOT regimen (fluorouracil, leucovorin, oxaliplatin, and docetaxel) showed superiority."

Dr. Estfan, who was not involved in the study, added, "This study evaluated NCDB data from patients with gastric cancer diagnosed between 2006 and 2017 (when ECF was the main perioperative chemotherapy)."

"While the data are intriguing, we do not know if these results hold true for more modern perioperative regimens like the currently used FLOT. We also do not know if a switch chemotherapy regimen for those with refractory disease would be beneficial," he told Reuters Health. "These are among many questions that would be better answered in the setting of controlled clinical trials."

Dr. Barzi noted that strengths of the study are the number of patients and institutions included and the long-term follow up. "The shortcomings include the retrospective nature of the study and the fact this is not a propensity-score-matching study," she added.

"In interpreting the findings of this study, one should keep in mind that the duration of chemotherapy before and after surgery is arbitrary and not driven by science. Therefore, with potential longer duration of chemotherapy prior to operation, the sensitive population could have ended up in the very sensitive population," Dr. Barzi cautioned. "The investigators were not able to look at other variables such as density and intensity of chemotherapy, patient weight, and the reasons for not giving chemotherapy after surgery."

Neither the corresponding author nor the several co-authors at Roswell Park responded to requests for comment.

SOURCE: JAMA Network Open, online November 19, 2021.