Prognostic and Predictive Value of Circulating Inflammation Signature in Non-Metastatic Nasopharyngeal Carcinoma: Potential Role for Individualized Induction Chemotherapy.

Abstract

PurposeWe sought to assess the prognostic and predictive value of a circulating inflammation signature (CISIG) and develop CISIG-based tools for predicting prognosis and guiding individualized induction chemotherapy (ICT) in non-metastatic nasopharyngeal carcinoma (NPC).Patients and MethodsWe retrospectively collected a candidate inflammatory biomarker panel from patients with NPC treated with definitive radiotherapy between 2012 and 2017. We developed the CISIG using candidate biomarkers identified by a least absolute shrinkage and selection operator (LASSO) Cox regression model. The Cox regression analyses were used to evaluate the CISIG prognostic value. A CISIG-based prediction model was constructed, validated, and assessed. Potential stratified ICT treatment effects were examined.ResultsA total of 1149 patients were analyzed. Nine biomarkers selected by LASSO regression in the training cohort were used to construct the CISIG, including hyaluronidase, laminin, procollagen III, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, high-density lipoprotein, lactate dehydrogenase, and C-reactive protein-to-albumin ratio. CISIG was an independent prognostic factor for disease-free survival (DFS; hazard ratio: 2.65, 95% confidence interval: 1.93–3.64; P < 0.001). High CISIG group (>−0.2) was associated with worse 3-year DFS than low CISIG group in both the training (67.5% vs 88.3%, P < 0.001) and validation cohorts (72.3% vs 85.1%, P < 0.001). We constructed and validated a CISIG-based nomogram, which showed better performance than the clinical stage and Epstein–Barr virus DNA classification methods. A significant interaction between CISIG and the ICT treatment effect was observed (P for interaction = 0.036). Patients with high CISIG values did not benefit from ICT, whereas patients with low CISIG values significantly benefited from ICT.ConclusionThe developed CISIG, based on a circulating inflammatory biomarker panel, adds prognostic information for patients with NPC. The proposed CISIG-based tools offer individualized risk estimation to facilitate suitable ICT candidate identification.