The Prognostic and Predictive Value of Pre-Treatment Total Lymphocyte Count in HPV+ Oropharyngeal Carcinoma Receiving Definitive (Chemo-) Radiation

Abstract

Evidence of prognostic importance of pre-radiotherapy (RT) total lymphocyte counts (TLC) and interaction with addition of cisplatin (CRT) in HPV-positive oropharyngeal carcinoma (HPV+OPC) is conflicting. Recent data suggest patients with high TLC may not benefit from the addition of chemotherapy (Price et al, JCO 2022). We assess the prognostic and predictive value of TLC in a large single center HPV+OCP cohort. All HPV+OPC patients treated at a single academic center with definitive RT/CRT between 2005-2018 were included. Pre-treatment TLC up to 6 weeks prior to RT start were considered. Multivariable analysis (MVA) was applied to assess the prognostic importance of TLC (continuous variable), adjusted for age, gender, performance status, TNM-8 stage, and smoking status in the CRT and RT subgroups. The actuarial rates of locoregional control (LRC), distant control (DC), and overall survival (OS) were calculated using Kaplan-Meier and competing risk methods, stratified by low vs high TLC (determined using Contal and O'Quigley method for optimal cutoff). Among 1153 eligible patients, 707 (61%) were treated with CRT. Median age was 59.7 (range 22.7-92.2) years. 526 patients were (46%) TNM-8 stage I, 366 (32%) stage II and 261 (23%) stage III. Median TLC was 1.6 x 109/L (range 0.1-8.5). Median follow-up was 5.5 years. On MVA, TLC was prognostic for patients receiving CRT (OS [adjusted hazard ration (aHR) 0.55 (0.38-0.79), p = 0.002], DC [aHR 0.57 (0.37-0.88), p = 0.011], LRC [aHR 0.57 (0.36-0.89), p = 0.014]) but not RT (OS [aHR 1.04 (0.82-1.31), p = 0.74], LRC [aHR 1.26 (0.86-1.85), p = 0.23], DC [aHR 0.87 (0.64-1.19), p = 0.4)]. The optimal TLC cut-off for OS with CRT was 1.9 x 109/L. Low vs high TLC patients receiving CRT had significantly inferior 5-year DC (87% vs 93%, p = 0.017) and OS (84% vs 90%, p = 0.026). The benefit of higher TLC was most evident in stage II disease (table 1). CRT vs RT improved OS for stage II/III disease at high and low TLC. Pre-treatment TLC is prognostic in a large cohort of HPV+OPC patients receiving CRT but not RT alone. Further investigation of the interaction of cisplatin and immune response during RT is warranted. The omission of chemotherapy based on TLC is not supported.