The Prognostic Study Of Circulating Lymphocyte Subtypes In The Treatment Of Liver Cancer With Radiotherapy Combined With Tirelizumab And Arotinib

Objective: Combination of immunotherapy with targeted therapy has been established as an effective approach for advanced hepatocellular carcinoma(HCC).The purpose of this study is to investigate the efficacy of radiotherapy combined with tislelizumab and anlotinib in patients with advanced liver cancer,as well as the relationship between circulating lymphocyte subtypes and tumor response and prognosis.Methods: A total of 46 patients with advanced HCC were enrolled from January 1,2019 to July 1,2022.Radiotherapy,the prescribed dose ranged from15 to 48 gray in 5 to 16 fractions for gross tumor volume,was initiated on days2-3 after tislelizumab plus anlotinib.Circulating lymphocyte subtypes pre-and post-treatment CD3+,CD3+CD4+,CD3+CD8+,CD16+CD56+,and CD19+were detected by flow cytometry.Results:(1)A total of 46 patients were included in this study.We observed a median follow-up time of 16.7 months and a m OS of 19.7 months.Complete remission(CR)was found in 2 cases(4.3%)and partial remission(PR)in 19 cases(41.3%).Disease stability(SD)was found in 9 cases(19.6%)and disease progression(PD)in 16 cases(34.8%).The ORR was 45.7%.(2)Mann-Whitney U test showed that the level of CD3+CD8+cells in the response group was significantly higher than that in the non-response group(p=0.016),while the level of CD4+/CD8+cells in the non-response group was significantly higher than that in the response group(p=0.017).The levels of CD3+,CD3+CD4+and CD19+cells in the response group were also higher than those in the non-response group(p>0.05).(3)Logistic model showed that CD3+CD8+,CD4+/CD8+were related to the objective remission rate of patients.(p=0.049,p=0.046,respectively);(4)The univariate COX analysis,AFP(p=0.041),lymph node metastasis(p=0.036),distant metastasis(p<0.001),and CD3+CD8+(p=0.038)were high-risk factors leading to poor prognosis of HCC.In multivariate COX analysis,lymph node metastasis(p=0.009),distant metastasis(p=0.006),and CD3+CD8+(p=0.009)are the key factors affecting the prognosis of patients with advanced liver cancer.(5)The level of CD3+CD8+cells was correlated with OS(p<0.05).Taking 145.0cells/u L as the critical value of CD3+CD8+,OS above the critical value is longer than OS below the critical value(21.0 months and 9.1 months respectively).P=(0.029),the risk of death decreased by 67.0%(HR 0.33,95% CI 0.12-0.94).(6)Radiotherapy combined with tirelizumab+arotinib in the treatment of advanced HCC mainly showed acute toxicity of grade 1-2,which was well tolerated by most patients.The most common were grade 1-2 Fatigue(47.8%),liver dysfunction(Aspartate transaminase and alanine transaminase increased by19.6% and 21.7% respectively)and Thrombo-cytopenia(17.4%).Conclusion:(1)The patients with advanced HCC treated by radiotherapy combined with tirelizumab+arotinib showed better survival benefits and lower toxicity;Triple therapy may be a feasible treatment for patients with advanced HCC.(2)The level of CD3+CD8+before treatment is an independent prognostic factor that affects ORR and OS of patients with advanced HCC treated with radiotherapy combined with tirelizumab and arotinib.(3)The curative effect of patients with high CD3+CD8+level before treatment is better than those with low CD3+CD8+level.(4)The change of CD3+CD8+level after treatment is closely related to the ORR of patients with advanced HCC treated by radiotherapy combined with tirelizumab+arotinib.