Impact of Immune, Inflammatory, and Nutritional Indices on Outcome in Patients with Cervical Cancer Treated with Definitive (Chemo)radiotherapy

Abstract

Systemic immune, inflammatory, and nutritional indices have been shown to be prognostic for outcome across a range of tumor sites. However, a comprehensive analysis of these markers in patients with cervical cancer treated with definitive (chemo)radiotherapy [(C)RT] has not been performed. We hypothesized that systemic immune, inflammatory, and nutritional indices may be associated with progression free survival (PFS) and overall survival (OS) in patients undergoing definitive (C)RT for cervical cancer. Patients with cervical cancer treated with definitive (C)RT from 1999 - 2015 were identified from a single cancer institution's retrospective clinicopathological database. Pre-treatment immune, inflammatory, and nutritional parameters were collected, and indices derived. Systemic immune-inflammation index (SII) = neutrophil count x platelet count / lymphocyte count(10^9/L); PLR = platelet count / lymphocyte count(10^9/L), NLR = neutrophil count / lymphocyte count (10^9/L); MLR = monocyte count / lymphocyte count (10^9/L); albumin to alkaline phosphatase ratio (AAPR) = serum albumin level (g/L)/alkaline phosphatase level (U/L) and prognostic nutritional index (PNI) = serum albumin (g/L) + 5 x lymphocyte count (10^9/L). Univariate analysis was first performed on each parameter as continuous variables for PFS and OS. For variables with statistically significant associations, ROC curves were analyzed to determine if an optimal cut point could be established for each outcome. Common cut points were then defined for each variable. PFS and OS were analyzed by the Kaplan-Meier method and the Log-Rank test. Multivariate analysis was performed using Cox regression with covariates of tumor stage, histology, and age. P-values of <0.05 were considered statistically significant. A total of 196 patients were identified; median follow-up 7 years. 131 (67%) had stage I-II and 65 (33%) stage III-IV disease. 187 (95%) received CRT and 9 (5%) RT alone. Higher SII (≤700 vs >700; p = 0.01), higher PLR (≤ 250 vs >250; p<0.001) and higher NLR (≤ 5 vs >5; p = 0.003) were associated with worse PFS. Higher SII [≤700 vs >700: 5y OS 74.9 vs 55.8; p = 0.02], higher PLR [≤ 250 vs >250: 5y OS 69.9% vs 42.0%; p<0.001] and higher NLR [≤ 5 vs >5: 5y OS 65.3% vs 51.0%; p = 0.01] were associated with worse OS. MLR, AAPR and PNI were not associated with outcome on univariate analysis. On multivariate analysis, SII and PLR were independently associated with both PFS [SII: HR 1.647 (CI 1.029-2.639), p = 0.038; PLR: HR 2.301 (95% CI 1.507 - 3.512), p = <0.001], and OS [SII: HR 1.649 (95% CI 1.009-2.696), p = 0.046; PLR: HR 2.212 (95% CI 1.416-3.455), p<0.001]; NLR did not remain statistically significant. SII and PLR, but not nutritional indices, were independently associated with PFS and OS in patients with cervical cancer treated with definitive (C)RT. Further evaluation of these systemic immune and inflammatory indices in a validation set will be required to better define their clinical utility.