Abstract
BackgroundThe 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).MethodsThe 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.ResultsPeripheral 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.ConclusionsHigher 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.
Highlights
The decrease in peripheral blood lymphocytes induced by radiation lessens the antitumour effect of the immune response, which might cause immunosuppression
In this study, we observed that a higher Min Minimum lymphocyte cell (ALC) after RT predicts better 1-year overall survival based on 59 hepatocellular carcinoma (HCC) patients
We demonstrated that Min ALCs during RT have an independent predictive value for the overall survival in HCC patients [11]
Summary
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). Ionizing radiation is one of the mainstay treatments in oncologic diseases, and its effects can lead to apoptosis of circulating lymphocytes, which lessens the antitumour effect of the immune response [4, 5]. The minimum value of absolute peripheral lymphocyte counts during RT treatment (Min ALC) has been considered a prognostic factor for recurrence and survival in several cancers [7,8,9,10]. We verified the value of Min ALC in predicting survival in hepatocellular carcinoma (HCC) patients [11]. The spleen, as a critical component of the immune system, plays an exclusive role in both the innate and adaptive immune systems [13]
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