Prediction of severe lymphopenia during chemoradiotherapy for esophageal cancer: development and validation of a pretreatment nomogram

Abstract Introduction In esophageal cancer patients, occurrence of severe radiation-induced lymphopenia during chemoradiotherapy has been associated with worse progression-free and overall survival. The aim of this study was to develop and validate a pretreatment clinical nomogram for the prediction of grade 4 lymphopenia. Methods A development set of consecutive patients who underwent chemoradiotherapy for esophageal cancer and an independent validation set of patients from another institution were identified. Grade 4 lymphopenia was defined as an absolute lymphocyte count (ALC) nadir during chemoradiotherapy of Results Among 860 included patients, 322 (37%) experienced grade 4 lymphopenia. Higher age, larger planning target volume in interaction with lower BMI, photon- rather than proton-based therapy, and lower baseline ALC were predictive in the final model (corrected c-statistic 0.76). External validation in 144 patients in whom 58 (40%) had grade 4 lymphopenia yielded a c-statistic of 0.71. Four nomogram-based risk groups yielded predicted risk rates of 10%, 24%, 43%, and 70%, respectively. Conclusions A pretreatment clinical nomogram was developed and validated for the prediction of grade 4 radiation-induced lymphopenia during chemoradiotherapy for esophageal cancer. The nomogram can risk stratify individual patients suitable for lymphopenia-mitigating strategies or potential future therapeutic approaches to ultimately improve survival.