Abstract

High baseline neutrophil-lymphocyte ratio (NLR) ≥ 3.5 was shown to be a negative prognostic factor in several solid cancers including MCC. The present study explores the prognostic and predictive role of basal NLR and its variations after adjuvant radiotherapy (RT) in stage II-III MCC patients (pts). We retrospectively identified 95 stage II-III MCC pts referred to our Institution from 2004 to 2019. All pts had Eastern Cooperative Oncology Group Performance Status 0 or 1 and were negative for active infections and autoimmune disease. No pts received concomitant immunosuppressive/immunostimulating drugs. We collected NLR values at the following timepoints: baseline at diagnosis, within one month before RT start and within one month after RT completion. Hazard ratios (HRs) were calculated using Cox’s proportional hazards regression model. Overall DFS and OS were 17,9 and 42.1 months (mos) respectively. All pts underwent radical surgery, followed by RT treatment (28.5%, 27 pts) or follow up (FU) alone (71,5%, 68 pts). Median FU was 42.6 (4.6 - 235.5) mos. Baseline NLR was significantly associated with DFS (HR 1.71 95%CI 1.43-2.05, p<0.001) and OS (HR 1.40 95%CI 1.11-1.77 p=0.004). In 11 out 27 (40.7%) pts who underwent RT, a decrease of post-RT NRL values was observed in comparison to pre-RT NLR values. There was a trend towards worse mDFS in pts whose NLR increased after RT compared to those whose NLR decreased after RT (mPFS 13.1 vs 52 mos, 95%CI 0.86- 8.62; HR 2.73; p= 0.087). In the multivariate model, older age and baseline NLR were both strongly associated with worse DFS (HR_NLR 1.63; 95%CI 1.34-1.99 p<0.001) and OS (HR_NLR 1.44; 95%CI 1.10-1.90 p=0.008). Despite being a retrospective study design, RT seems to be able to modulate the frequencies of peripheral immune subsets and correlates with the shift to a more favorable peripheral immune profile. Further studies are needed to determine the role of NLR as potential prognostic and predictive biomarkers to consider when selecting MCC pts for adjuvant treatment.

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