Lymphocyte-Sparing Effect of Proton Therapy in Patients with Esophageal Cancer Treated with Definitive Chemoradiation

Purpose: To assess whether radiation treatment modality with proton beam therapy (PBT) or intensity-modulated radiation therapy (IMRT) is associated with lymphopenia in patients treated with definitive chemoradiation for esophageal cancer.

Methods and materials: Patients with esophageal cancer treated with bimodality therapy (n = 448) between 2004 and 2016 were retrospectively reviewed. Patients treated with PBT were matched by propensity score with those treated with IMRT, based on key patient and disease factors, and stratified by clinical disease stage. Patients who developed early, distant metastatic disease within 1 month of completing radiation were excluded. Univariable and multivariable logistic regression were used to identify variables associated with increased risk of grade 4 lymphopenia. Multivariable Cox proportional hazards regression was used to assess factors associated with overall survival, disease-free survival, and locoregional relapse-free survival.

Results: Patients who had IMRT and PBT matched by propensity score (n = 220) were not different with respect to age, sex, stage, performance status, tumor location, histology, tumor target volume, or induction chemotherapy. Treatment with IMRT, compared with PBT (odds ratio [OR], 2.13; 95% confidence interval [95% CI], 1.19-3.81; P = .01), increased age (OR, 1.039/y increase; 95% CI, 1.003-1.076; P = .03), and greater planning target volume (OR, 3.47 per 1-unit increase in log (planning target volume); 95% CI, 1.67-7.21; P < .001), was associated with increased risk of grade 4 lymphopenia. Radiation modality was associated with lymphocyte reduction in patients with tumors in the lower esophagus (P = .005) but not for those with tumors in the upper or middle esophagus (P = 0.32).

Conclusions: In patients with esophageal cancer treated with definitive chemoradiation, PBT reduces the risk of severe, treatment-related lymphopenia, particularly in tumors of the lower esophagus.