The decrease in peripheral blood lymphocytes induced by radiation lessens the antitumour effect of the immune response, which might cause immunosuppression. We aimed to investigate the correlation between the decrease in peripheral blood lymphocytes during radiotherapy (RT) and the spleen irradiation dose in patients with hepatocellular carcinoma (HCC). The subjects were 59 patients with HCC who had received RT from 2005 to 2014. The Min ALC (minimum value of absolute counts for peripheral blood lymphocytes) was collected from the routine workup for each patient prior to RT and weekly during RT. Spleen dose-volume variables, including the percentage of the organ volume receiving ≥ n Gy (Vn) and the mean spleen dose (MSD), were calculated using Eclipse treatment planning. Potential associations between dosimetric variables and the Min ALC were assessed by multiple linear regression analysis. Peripheral lymphocytes decreased during RT (P < 0.001). The Min ALC correlated with the MSD (P = 0.005), spleen V5 (P = 0.001), spleen V25 (P = 0.026) and spleen V30 (P = 0.018). Controlling for the Karnofsky performance status (KPS), sex, age, Child-Pugh grade, total dose and tumour stage, a multiple linear regression model with bootstrap analysis of 1000 replicates showed that only the spleen V5 was correlated with the decrease in the Min ALC (P < 0.05). According to the receiver-operating characteristic (ROC) curve analysis, the predictive cutoff values of the MSD, V5, V25 and V30 of the spleen for the Min ALC were 227.72 cGy, 17.84, 0.98 and 0.42%, respectively (P = 0.002, P = 0.004, P = 0.007 and P = 0.002, respectively). Furthermore, an MSD ≥ 227.72 cGy (OR = 14.39; 95% CI, 12.18 to 16.60) and V5 (OR = 7.99; 95% CI, 6.91 to 9.07) of the spleen significantly predicted the Min ALC. Higher spleen irradiation doses were significantly correlated with lower Min ALC during RT for HCC. V5 should be limited in clinical practice. Maximum sparing for spleen irradiation during RT is recommended to preserve peripheral blood lymphocytes, which may decrease immunosuppression.

To investigate the potential impact of fractionation regimes and overall treatment time (OTT) on lymphopenia during definitive radiotherapy (RT) and its associations with patient outcomes in non-small cell lung cancer (NSCLC). Subjects consisted of 115 patients who had received definitive chemoradiation therapy (CRT) with different doses and fractions for unresectable stage III NSCLC. Clinical and laboratory records were reviewed to assess the changes in total lymphocyte counts (TLCs) during definitive RT. The associations of the TLCs with the clinical and treatment features, and outcomes were analyzed. The median reduction of TLCs in the entire cohort was 1300 cells/μL (interquartile range [IQR], 950–1510 cells/μL). Of all patients, 63 (54.8%) experienced severe lymphopenia (SL) (TLC nadir < 500 cells/μL), which occurred at a median of the 5th week following RT initiation, not at the completion of RT or upon treatment with maximal doses. SL risk was increased over the first 5 weeks (odds ratio [OR] = 3.455, P = 0.007), after which, no increased risk was observed (OR = 0.562, P = 0.216). The median TLCs remained low and failed to recover to the initial normal values of their pre-RT level after 2 months of RT completion. Patients without SL exhibited significantly improved progression-free survival (hazard ratio [HR] = 0.544, P = 0.010) and overall survival (HR = 0.463, P = 0.011) after controlling for confounding variables in multivariate analyses. The incidence of SL was significantly lower (71.1% reduction in risk (OR = 0.289, P = 0.007)) in patients who received hypofractionated RT with an OTT within 4 weeks, compared to those who had an OTT of more than 4 weeks (32.1% vs 62.1%, P = 0.006). Multivariate analyses revealed that OTT within 4 weeks (OR = 0.322, P = 0.032) was significantly associated with a decreased risk of developing SL after controlling for confounding factors. Hypofractionated RT was significantly associated with a decreased risk of SL and improved survival during definitive radiotherapy for unresectable stage III NSCLC.