J. Li; Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an, China., China
Purpose/Objective(s): Inflammation biomarkers (IBs) at various cancers, including esophageal squamous cell carcinoma (ESCC), is associated with prognosis. The impact of definitive (chemo)radiotherapy (CRT) on IBs is unknown. In addition, the prognostic value of the longitudinal dynamic trajectories of IBs before, during, and after CRT is unclear. This multi-center study aimed to investigate the longitudinal dynamic trajectories of IBs and its prognostic value in ESCC. Materials/
Methods: 944 patients with ESCC receiving CRT between 2008-2021 in two high-volume centers were included. At four distinct time points (pre-CRT, during CRT at week 2, during CRT at week 4, and post-CRT), IBs were calculate, including systemic immune-inflammatory index (SII), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR). Group-based trajectory modelling (GBTM) was used to analyze IBs at four timepoints and identify distinct longitudinal dynamic subgroups. Kaplan-Meier was used for survival analysis. Primary outcomes were overall survival (OS) and Local recurrence-free survival (LRFS). Nomograms based on Least Absolute Shrinkage and Selection Operator (LASSO) regression-selected variables predicted survival and were cross-validated. Results: Similar change trend in SII, NLR, and PLR pre-/during-/post-CRT were observed. These IBs increased significantly from baseline levels at week 2 and week 4 during CRT (P<0.001), and return or near to baseline levels after CRT. GBTM identified two trajectories of SII and LMR, three trajectories of NLR and PLR. The longitudinal dynamic trajectories of SII, NLR and PLR were significantly correlated with OS and LRFS in ESCC patients (P<0.05). Using LASSO regression method, 11 variables were identified: age, tumor length, tumor location, T stage, N stage, PS, radiotherapy technique, concurrent chemotherapy, as well as the trajectory groups of SII, NLR and PLR, all of which were recognized as prognostic factors associated with survival. In multivariable survival analysis, tumor location (HR, 1.400 and 1.370), T stage (HR, 2.670 and 2.510), current chemotherapy (HR, 0.490 and 0.500) and the longitudinal trajectories of SII (HR, 1.250 and 1.310) were independently associated with OS and LRFS (all P<0.05). The C-index of the nomograms was 0.661 for OS and 0.655 for LRFS. After being cross-validated, the C-index were 0.647 and 0.646 for OS and LRFS, respectively, which were inferior to those models performance conducted by directly combining IBs at multiple static time points (0.641 for OS, and 0.640 for LRFS). The AUC values for predicting 1-, 3-, and 5-year OS and LRFS were 0.707, 0.711, 0.706, and 0.703, 0.706, 0.684, respectively. The calibration curve for the probability of survival showed good agreement between Predicted probability and actual survival. Conclusion: The longitudinal dynamic trajectories of IBs have the potential to serve as more accurate prognostic indicators for ESCC patients undergoing CRT.
