In a study reported in JAMA Oncology, Cheng et al found that higher levels of inflammatory biomarkers measured after surgery—but before receipt of chemotherapy—were associated with poorer outcomes in patients with stage III colon cancer enrolled in the CALGB/SWOG 80702 trial of adjuvant chemotherapy.
Study Details
In the trial, patients were randomly assigned in a 2 × 2 design to adjuvant (1) fluorouracil, leucovorin, and oxaliplatin for 3 months vs 6 months and (2) daily celecoxib (COX-2 inhibitor, nonsteroidal anti-inflammatory drug [NSAID]) vs placebo for 3 years between June 2010 and November 2015; follow-up was continued through August 2020. No significant difference in survival among groups was observed, with patients thus being combined for the current analysis.
A total of 1,494 patients with plasma samples available for inflammatory biomarker assays were included in the analysis. Levels of interleukin 6 (IL-6), soluble tumor necrosis factor α receptor 2 (sTNF-αR2), and high-sensitivity C-reactive protein (hsCRP) were measured 3 to 8 weeks after surgery but prior to chemotherapy random assignment. The primary outcome measure was disease-free survival according to biomarker levels. Analyses were adjusted for disease and patient characteristics, including use of low-dose aspirin and other NSAIDs.
Key Findings
Compared to patients with biomarker levels in the lowest quintile, those with levels in the highest quintile had significantly poorer disease-free survival for IL-6 (adjusted hazard ratio [HR] = 1.52, 95% confidence interval [CI] = 1.0–-2.14, P = .01 for trend), sTNF-αR2 (adjusted HR = 1.77, 95% CI = 1.23–2.55, P < .001 for trend), and hsCRP (adjusted HR = 1.65, 95% CI = 1.17–2.34, P = .006 for trend). No significant interaction was observed between biomarkers and celecoxib treatment for disease-free survival.
For recurrence-free survival, adjusted hazard ratios for the highest vs lowest quintile were 1.68 (95% CI = 1.07–2.65, P = .08 for trend) for IL-6, 1.54 (95% CI = 1.04–2.28, P = .001 for trend) for sTNF-αR2, and 1.73 (95% CI = 1.11–2.68, P = .03 for trend) for hsCRP. For overall survival, adjusted hazard ratios for the highest vs lowest quintile were 1.54 (95% CI = 1.05–2.25, P = .03 for trend) for IL-6, 2.33 (95% CI = 1.40–3.89, P = .02 for trend) for sTNF-αR2, and 1.56 (95% CI = 1.07–2.26, P = .003 for trend) for hsCRP.
The investigators concluded, “This cohort study found that higher inflammation after diagnosis was significantly associated with worse survival outcomes among patients with stage III colon cancer. This finding warrants further investigation to evaluate whether anti-inflammatory interventions may improve colon cancer outcomes.”
Jeffrey A. Meyerhardt, MD, MPH, of Dana-Farber Cancer Institute, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the National Cancer Institute, Pfizer, and others. For full disclosures of the study authors, visit jamanetwork.com.
