The Association Between Absolute Lymphocyte Counts With Outcomes During Radiotherapy In Unresectable Hepatocellular Carcinoma

Part ? Minimum absolute lymphocyte counts during radiation are associated with a worse prognosis in patients with unresectable hepatocellular carcinomaObjectives:Peripheral blood lymphocytes play an important role in anti-tumour immunity.We examined the relationship between the minimum absolute lymphocyte counts(Min ALCs)during radiotherapy(RT)and clinical outcomes in patients with hepatocellular carcinoma(HCC).Methods:Data from a total of 69 HCC patients who had received RT were retrospectively analysed.Peripheral blood lymphocytes were measured before RT,weekly during RT and after RT.Regression and mixed effects models were used to assess the relationships with and potential predictors of overall survival(OS).Receiver operating characteristic curve analysis was used to define optimal cut-off points of continuous variables for outcomes.Results:The median follow-up was 30 months(range,4-68 months).The median survival time(MST),1-year OS rate and 2-year OS rate of the whole group were 25 months,51%and 39%,respectively.The average circulating lymphocyte counts declined during RT(1493.19 vs.503.48 cells/?l,P<0.001).A lower Min ALC was associated with worse OS(P=0.001),with a cut-off value of 450 cells/?l(sensitivity and specificity,50%and 70.6%,respectively).The MSTs,1-year OS rates and 2-year OS rates were 15 months vs.47 months,27%vs.78%and 4%vs.71%for patients with relatively lower(?450 cells/?l)and higher Min ALCs(>450 cells/?l),respectively(P<0.001).After adjusting for potential confounders,multivariate Cox regression analysis demonstrated that Min ALC independently predicted patients overall survival(HR,0.32;95%CI,0.15-0.69).Conclusions:Lower Min ALCs during RT may act as a worse prognostic factor for HCC after RT.Part ? Radiation-related lymphopenia is associated with spleen irradiation dose during radiotherapy in patients with hepatocellular carcinomaBackground: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).Methods:The subjects were 56 patients with HCC who had received RT from 2009 to 2015.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.Results: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%Cl,6.91 to 9.07)of the spleen significantly predicted the Min ALC.Conclusions: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.