Research Article: Development and validation of a pre-chemotherapy nomogram integrating systemic immune-inflammation index and prognostic nutritional index to predict severe adjuvant toxicity in colorectal cancer
Abstract:
Severe toxicities frequently complicate adjuvant chemotherapy for stage II/III colorectal cancer (CRC), leading to dose reductions and compromised outcomes. While the Systemic Immune-Inflammation Index (SII) and Prognostic Nutritional Index (PNI) are established prognostic markers, their value in predicting chemotherapy tolerance, reflecting physiological reserve, remains understudied. This study evaluated baseline pre-chemotherapy SII and PNI to construct a validated nomogram for predicting severe chemotherapy-induced toxicity (CIT).
We retrospectively analyzed 306 patients with stage II/III CRC receiving oxaliplatin-based adjuvant chemotherapy (CAPOX or mFOLFOX6). The primary endpoint was grade 3–4 adverse events. Optimal pre-chemotherapy cut-off values were determined via ROC analysis and the Youden index. Independent predictors from multivariate logistic regression were integrated into a nomogram. Performance was assessed via discrimination (apparent and optimism-corrected AUC via 500 bootstrap resamples), calibration (plots and Brier score), and clinical utility (Decision Curve Analysis, DCA).
Severe CIT occurred in 78 (25.5%) patients. Baseline high SII (adjusted OR = 8.56, P < 0.001) and low PNI (adjusted OR = 4.69, P < 0.001) were independent risk factors. The nomogram (Age, SII, PNI) showed excellent discrimination (apparent AUC: 0.868; optimism-corrected AUC: 0.867) and strong calibration (Brier score: 0.1114). Patients in the high-risk group (probability ?37.4%) experienced a significantly shorter median therapy duration (4.1 vs. 4.8 months) and a markedly lower oxaliplatin relative dose intensity (median 76.7% vs. 100.0%) compared to the low-risk group (both P < 0.001). DCA confirmed the nomogram offered greater net clinical benefit than single markers or traditional assessments.
Pre-chemotherapy elevated SII and decreased PNI are robust predictors of severe toxicity. The proposed nomogram is a reliable, cost-effective tool for risk stratification, enabling risk-adapted strategies like nutritional prehabilitation, dose adjustment, and prophylactic growth factor support for high-risk CRC patients.
Introduction:
Severe toxicities frequently complicate adjuvant chemotherapy for stage II/III colorectal cancer (CRC), leading to dose reductions and compromised outcomes. While the Systemic Immune-Inflammation Index (SII) and Prognostic Nutritional Index (PNI) are established prognostic markers, their value in predicting chemotherapy tolerance, reflecting physiological reserve, remains understudied. This study evaluated baseline pre-chemotherapy SII and PNI to construct a validated nomogram for predicting severe…
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