Circulating CD4:CD8 Ratio is Prognosticator of Response to Total Skin Electron Beam Radiation in Mycoses Fungoides

Abstract

A lower proportion of CD8+ tumor infiltrating lymphocytes in mycoses fungoides (MF) patients is associated with poorer survival. However, whether circulating lymphocyte subsets, as reflected by circulating CD4:CD8 ratio, is a prognostic factor for radiotherapy response is not known. We hypothesized CD4:CD8 ratio is prognostic of outcomes in MF patients treated with total skin electron beam therapy (TSEBT) and performed multi-institutional retrospective analysis. We retrospectively examined 124 MF patients from MD Anderson Cancer Center (MDACC) and Yale Cancer Center (YCC) treated with TSEBT from 2001-2014. Circulating CD4:CD8 ratio (103/μL) was based on serum analysis obtained before TSEBT. TSEBT was delivered with 9mEV electrons from low (12 Gy) to conventional (≥12 Gy) doses. Cutaneous clinical treatment response was assessed with the modified Severity Weighted Assessment Tool (mSWAT). Post-treatment mSWAT decrease of ≥75% was classified as near complete response (CR) and mSWAT decrease of <75% was considered as having a partial response (PR). Receiver operating characteristic analysis determined an optimal CD4:CD8 threshold value to predict TSEBT response in discovery cohort. Multivariate logistic regression examined the association between CD4:CD8 and TSEBT response. 71.8% and 28.2% of all patients achieved CR and PR to TSEBT, respectively. Higher CD4:CD8 ratio predicted poorer response: Median CD4:CD8 in patients with PR was 4.59 (interquartile range: 2.50-4.59) vs. 1.95 (1.10-3.09) in patients with CR (p=0.002). A threshold CD4:CD8 value of 4.4 optimally discriminated patients with CR vs. PR (sensitivity 90% specificity 59% AUC =0.71; P=0.002). 34.5% of patients with CD4:CD8 ≥4.4 (n=29), achieved CR compared to 83.2% of patients with CD4:CD8 < 4.4 (n=95). Among patients with low CD4:CD8 <4.4 (n=73), 74% achieved CR with low dose TSEB vs. 93% with conventional dose TSEB (Chi-square P=0.02); (Breslow Day P=0.26 for the modifying effect of CD4:CD8 on TSEB dose). After adjusting for baseline mSWAT, stage, and TSEB dose, CD4:CD8 remained a significant predictor of TSEB response (OR=0.113, 95% CI 0.04-0.31, p<0.001 for low vs. high CD4:CD8). For MF patients treated with TSEBT, CD4:CD8 ratio was an important prognostic factor of TSEBT treatment response at two high-volume academic centers. The potential for CD4:CD8 ratio’s modifying effect on the efficacy of low- vs. conventional-dose TSEBT warrants further investigation as a possible biomarker to inform radiation treatment decisions.