Elevated levels of inflammatory biomarkers after surgery are associated with worse outcomes for patients with stage III colon cancer, according to research published in JAMA Oncology

Researchers found that elevated levels of interleukin 6 (IL-6), soluble tumor necrosis factor α receptor 2 (sTNF-αR2), and high sensitivity C reactive protein (hs CRP) were associated with an increased risk of colon cancer recurrence and death. 

This study included 1494 patients with stage III colon cancer who were enrolled in an adjuvant chemotherapy trial (ClinicalTrials.gov Identifier: NCT01150045). 


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Researchers measured the aforementioned inflammatory biomarkers — IL-6, sTNF-αR2, and hsCRP — 3 to 8 weeks after patients underwent surgery but before they were randomly assigned to chemotherapy. Patients were divided into quintiles according to plasma concentration levels of the biomarkers.  

For all 3 biomarkers, patients in the highest inflammation quintile had a significantly higher risk of death or recurrence than patients in the lowest quintile: 

  • For IL-6, the adjusted hazard ratio (aHR) was 1.52 (95% CI, 1.07-2.14; P =.01) 
  • For sTNF-αR2, the aHR was 1.77 (95% CI, 1.23-2.55; P <.001)
  • For hsCRP, the aHR was 1.65 (95% CI, 1.17-2.34; P =.006). 

When the researchers looked at recurrence alone, they found that increased inflammation was generally associated with an increased risk of recurrence:

  • For IL-6, the aHR for recurrence was 1.68 (95% CI, 1.07-2.65; P =.08) 
  • For sTNF-αR2, the aHR was 1.54 (95% CI, 1.04-2.28; P =.001)
  • For hsCRP, the aHR was 1.73 (95% CI, 1.11-2.68; P =.03). 

Increased inflammation was also associated with an increased risk of death alone:

  • For IL-6, the aHR for death was 1.54 (95% CI, 1.05-2.25; P =.03) 
  • For sTNF-αR2, the aHR was 2.33 (95% CI, 1.40-3.89; P =.02)
  • For hsCRP, the aHR was 1.56 (95% CI, 1.07-2.26; P =.003). 

“Our findings from a large, well-designed, prospective cohort study provide compelling observational evidence that higher inflammation after diagnosis was significantly associated with worse survival among patients with stage III colon cancer,” the researchers wrote. “Further investigation is warranted to evaluate whether anti-inflammatory interventions may improve colon cancer outcomes.”  

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 

Reference

Cheng E, Shi Q, Shields AF, et al. Association of inflammatory biomarkers with survival among patients with stage III colon cancer. JAMA Oncol. Published online January 26, 2023. doi:10.1001/jamaoncol.2022.6911