The Incidence of Severe Radiation-Induced Lymphopenia during Chemoradiotherapy for Stage Ⅲ Non-Small Cell Lung Cancer: A Comparative Study of Proton Versus Photon-Based Radiotherapy

To investigate the incidence of severe radiation-induced lymphopenia (SRL) and the survival in patients with stage Ⅲ non-small cell lung cancer treated with concurrent chemoradiotherapy with passive scattering proton beam (PSPT) or photon-based radiotherapy (XRT) including 3D-CRT and IMRT.We conducted a retrospective cohort study including 355 patients who received definitive concurrent chemoradiotherapy with PSPT (n = 38) or XRT (n = 317) at our institution between January 2010 and December 2020. SRL during concurrent chemoradiotherapy was defined as absolute lymphocyte counts (ALCs) of <500 cells/mm3. Propensity score matching (PSM) analysis was performed to adjust for the patient characteristics between the PSPT and XRT groups. Propensity scores were calculated using age, sex, PS (0-1 vs. 2), primary tumor location (upper/middle vs. lower lobe), pathology (Adeno vs. Others), PTV volume, ALCs at pretreatment, year of treatment (before vs. after July 2018, when durvalumab approved in Japan), and platinum-based chemotherapy regimen (CDDP based vs. CBDCA based). After PSM, the incidence of SRL and the overall survival (OS) were analyzed.The GTV and PTV volumes were significantly lower in the PSPT group than in the XRT group (median, 57 vs. 103 mm3; p < 0.05, 322 vs. 399 mm3; p < 0.05, respectively). ALCs at pretreatment were significantly lower in the PSPT group than in the XRT group (median, 1531 vs. 1718 cells/mm3; p < 0.05). SRL was observed in 275 patients (87%) in the XRT group and 27 patients (71%) in the PSPT group (p < 0.05). After PSM, PSPT significantly reduced the incidence of SRL compared to XRT (68.6 % vs. 88.6 %, p < 0.05), and the patients without SRL may have better 3-year OS than those with SRL (71.1 % vs. 55.3 %; p = 0.062).Compared with XRT, PSPT significantly reduced the incidence of SRL, and the patients without SRL had a good prognosis.