Effect of Perioperative Interleukin-6 and Tumor Necrosis Factor- on Long-Term Outcomes in Locally Advanced Gastric Cancer: Results from the CLASS-01 Trial.

Background: Little is known about the relation between perioperative inflammatory changes and long-term survival in cancer patients. The aim of the study was to assess the association of perioperative serum interleukin-6 (IL6) and tumor necrosis factor- (TNF) levels with the 5-year overall survival in locally advanced gastric cancer.

Methods: The 135 eligible patients in one center of Nanfang Hospital were retrieved from CLASS-01 trial (NCT01609309), an open-label, multicenter, randomized clinical noninferiority trial conducted at 14 centers in China. Serum IL6 and TNF levels were tested before surgery, and on postoperative day (POD) 1, POD3, and POD5, respectively, referring to IL6_0, IL6_1, IL6_3, and IL6_5 and TNF_0, TNF_1, TNF_3, and TNF_5. Kaplan-Meier methods and COX models were used for survival analysis.

Results: High levels of IL6_0 (≥3.67 pg/mL) and TNF_0 (≥14.8 pg/mL) presented worse disease-free survival (DFS) ( = 0.0057 for IL6_0 and = 0.0014 for TNF_0) and overall survival (OS) ( = 0.0021 for IL6_0 and = 0.0019 for TNF_0). Both high IL6_0 and high IL6_5 levels indicated worse prognosis than other combinations ( = 0.0045 for DFS and = 0.0022 for OS). In multivariate analysis, both high IL6_0 and high IL6_5 levels were significantly associated with poor DFS (HR = 4.29, 95% CI: 1.42-12.95, = 0.01) and OS (HR = 4.11, 95% CI: 1.35-12.49, = 0.013) after adjustment of tumor stage and TNF_0. Also, high IL6_5 level was identified as the independent-related factor for postoperative infectious complications (OR = 2.69, 95% CI: 1.03-7.01, = 0.043).

Conclusions: Perioperative high serum IL6 and TNF levels are negatively associated with 5-year survival outcomes in patients with locally advanced gastric cancer, indicating the potential survival benefits from perioperative anti-inflammatory treatment.