Chronic Inflammatory Comprehensive Signature Predicts Oxaliplatin and 5-Fluorouracil Benefit in Early Colorectal...

Area of Science:

• Oncology
• Cancer Biomarkers
• Inflammation and Cancer

Background:

• Adjuvant chemotherapy (ACT) improves outcomes in stage II-III colorectal cancer (CRC).
• Predictive biomarkers for 5-fluorouracil (5-FU) and oxaliplatin response are needed.
• Inflammatory indices may offer prognostic and predictive value.

Purpose of the Study:

• To evaluate the prognostic role of 12 inflammatory indices in stage II-III CRC.
• To develop and validate a novel Chronic Inflammatory Comprehensive Signature (CICS) for predicting ACT response.
• To guide personalized ACT regimen selection based on CICS stratification.

Main Methods:

• Analysis of three independent cohorts (1676 patients).
• Development of CICS using multivariable Cox regression.
• Comparison of recurrence-free survival (RFS) and overall survival (OS) between CICS-L and CICS-H subgroups.

Main Results:

• Novel inflammatory ratios and scores independently predicted prognosis.
• CICS predicted outcomes, with improved accuracy when combined with CEA-CA19-9.
• CICS-H patients showed reduced chemosensitivity; benefits were mainly in CICS-L.
• Optimal ACT regimens varied by stage and CICS status.
• CICS strategy improved ACT selection and therapeutic efficacy.

Conclusions:

• CICS-quantified inflammation inversely correlates with 5-FU/oxaliplatin responsiveness.
• A CICS-guided strategy maximizes survival and enables precision de-escalation of chemotherapy.
• CICS establishes a biomarker-driven paradigm for personalized CRC postoperative management.