The relationship of lymphocyte recovery and prognosis of esophageal cancer patients with severe radiation-induced lymphopenia after chemoradiation therapy

Introduction: Radiation-induced lymphopenia (RIL) during therapy is associated with poor prognosis but is often temporary and resolves after treatment completion in esophageal cancer. How lymphocyte recovery contributes to prognosis is unknown. Methods: We reviewed 755 patients with stage I-III esophageal carcinoma who received concurrent chemoradiation therapy (CRT) with or without surgery in 2004–2015. Complete blood counts were obtained before, during, and at first follow-up after CRT. Lymphopenia was graded per the Common Terminology Criteria for Adverse Events v4.03 during CRT (G) and as recovery after CRT (G _r ). Clinical factors and lymphopenia grade were tested for association with survival in univariable and multivariable Cox proportional hazard regression analyses. Results: During CRT, 294 patients (38.9%) had G4 lymphopenia; by the first follow-up, 406 patients (53.8%) had recovered (G _r 0-1). Relative to patients with G0-3 lymphopenia during CRT, G4 lymphopenia independently predicted worse OS in multivariable analyses. However, lymphocyte recovery was not associated with a better prognosis. Patients with G4 lymphopenia during CRT and recovery (G _r 0-1) afterward still had poorer 5-year OS rate than patients with G0-3 during CRT without recovery (G _r 2-4) afterward (36.6% vs. 51.9%, HR = 1.40, 95% CI 1.04–1.89, P = 0.027). Moreover, the lymphocyte recovery ability (post-CRT ALC divided by pre-CRT ALC) was not affected by lymphopenia grade during CRT (0.66 in G0-3 vs. 0.65 in G4, p = 0.473). Among patients with G4 lymphopenia during treatment, lymphocyte recovery was only associated with pre-CRT lymphocyte counts. Conclusion: Lymphocyte count recovery after CRT does not alter the poor long-term outcomes brought about by high-grade lymphopenia during CRT.