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Patients (pts) affected by locally advanced rectal cancer (LARC) may respond differently to neoadjuvant chemoradiotherapy (nCRT). The identification of reliable biomarkers for oncologic outcomes could help in the development of risk-adapted treatment strategies. There is evidence of a role of inflammation parameters as prognostic factors for survival outcomes in different cancer types. Hemo-eosinophils inflammation (HEI) index, comprising systemic inflammation index (SII), hemoglobin (Hb) and eosinophils levels, was recently highlighted as a predictor of disease-free survival (DFS) and overall survival (OS) in anal cancer pts treated with CRT. The aim of the present study is to evaluate baseline inflammatory markers as prognostic factors in a large cohort of LARC pts.

Pts undergoing nCRT for LARC from January 2010 to December 2019 were retrospectively analyzed. Pts underwent long-course RT with chemotherapy based on fluoropyrimidine ± oxaliplatin. Surgery was performed after re-evaluation at least 8 weeks after the end of CRT. Adjuvant chemotherapy was an option, depending on risk factors. Pts with a follow-up time of less than 2 years were excluded. We collected data related to clinical and laboratory parameters, disease stage, treatments characteristics, pathological staging and patients’ status. Pre-treatment blood samples were taken and inflammatory markers were calculated including HEI, SII, NLR (neutrophil/lymphocyte ratio), PLR (platelet/lymphocyte ratio) and MLR (monocyte/lymphocyte ratio). The inflammatory marker values were discretized into a variable number of equal-sized buckets and processed through logistic regressions in order to determine optimal bucket numbers and respective cut-offs in reference to the explored risk factors: OS, DFS, metastasis-free survival (MFS) and local control (LC). 

A total of 679 pts were eligible for analysis: 408 (6.1%) were males, median age was 65 years (range 23-91) [Table 1]. RT was delivered with a median dose of 55 Gy (range 19.8-58.5). In our analysis [Table 2] we found a significative association between SII, NLR and HEI with OS (p-value of 0.04, 0.01, and 0.002 respectively). We identified a cut-off value for SII and NLR (615.08 and 2.55, respectively); pts with a lower value showed a worse OS compared with those with higher baseline values. Regarding HEI index, pts were divided into 2 groups according to their score (0-1 and 2-3 respectively); pts with ≥2 had a worse OS. PLR and MLR failed to show significative association with OS; we also failed to observe association between all markers and DFE, MFS and LC.

These data suggest a possible correlation between baseline inflammatory parameters and oncological outcomes, in particular OS, possibly related to host response to the tumor. A deeper insight into both systemic and local inflammatory markers could lead to the development of decision making tools.