ALNCR.TNM as a Novel Prognostic Tool for Cancer Survival.

BACKGROUND

Systemic inflammation is associated with cancer prognosis, but commonly used inflammatory indices show limited discrimination across heterogeneous malignancies. We developed and validated a novel inflammatory burden index, ALNCR, and tested whether integrating ALNCR with TNM stage improves overall survival (OS) prediction.

METHODS

We analysed 6374 adults with cancer from the multicentre INSCOC cohort (2013-2021), randomly split into a training cohort (n = 4464) and internal validation cohort (n = 1910), and an external validation cohort from Fujian Cancer Hospital (n = 759). Female proportions were 39.0%, 41.2% and 32.0%, and median ages were 60, 60 and 58 years, respectively; Stage IV disease accounted for 45.4%, 45.8% and 64.8%. ALNCR was defined as (albumin × lymphocyte) / (neutrophil × C-reactive protein). Discrimination was assessed using C-index and time-dependent AUC, with comparisons to NLR, PLR, CAR, SII and PNI. A combined model (ALNCR.TNM) used ALNCR (cutoff 3.21) and TNM stage (I/II vs. III/IV); incremental value was quantified by net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

RESULTS

ALNCR showed the highest discrimination for OS among evaluated indices (C-index 0.645 [95% CI 0.631-0.658] in training; 0.666 [0.645-0.686] in internal validation; and 0.657 [0.624-0.690] in external validation). High ALNCR (≥ 3.21) was associated with longer OS than low ALNCR (median OS not reached vs. 22.3 months; log-rank p < 0.001). After multivariable adjustment, high ALNCR remained associated with lower mortality (HR 0.56 [0.51-0.61], 0.50 [0.43-0.58] and 0.53 [0.42-0.67] across the three cohorts; all p < 0.001). Adding ALNCR to TNM improved prediction over TNM alone (ΔC-index +0.021; NRI 0.067, p = 0.010; IDI 0.004, p < 0.001) and stratified patients into four risk groups (p < 0.0001), with consistent associations across major cancer types and clinical strata.

CONCLUSIONS

ALNCR is a simple inflammation-based prognostic index that outperforms conventional inflammatory markers for OS prediction. Integrating ALNCR with TNM stage improves risk stratification and prognostic accuracy, supporting clinical implementation via a nomogram and web-based calculator.