| Primary liver cancer is the third leading cause of cancer-related death worldwide,mainly including hepatocellular carcinoma(HCC),intrahepatic cholangiocarcinoma(ICC)and combined hepatocellular-cholangiocarcinoma(cHCC-CCA).Unlike HCC and ICC,cHCC-CCA is a rare primary liver cancer,accounting for 0.4%-14.2%of primary liver cancers,and huge heterogeneity exists in morphology,immunophenotype,molecular,radiological,and clinical features,and it is a rare type of tumor that is worth studying.However,there is currently no clear treatment guideline for this type of tumor.Radical resection is the only curative option for patients,relapse usually occurs very quickly,and the factors that affect postoperative recurrence and survival are not yet clear.For patients with recurrent or initially unresectable cHCC-CCA,systemic therapy is the main treatment option.However,compared with the rapidly developing research on immunotherapy in the fields of HCC and ICC,immunotherapy is still blank in the field of cHCC-CCA and lacks relevant information of clinical cohort reports.This thesis mainly includes a retrospective study on the prognosis analysis of cHCC-CCA patients after radical resection and the efficacy and safety analysis of immunotherapy-based systemic therapy in patients with advanced unresectable cHCC-CCA.In the surgical cohort,the median overall survival(mOS)of 95 patients after curative resection was 26.8 months,and the median recurrence-free survival(mRFS)was 7.27 months.Most patients relapsed within 1 year after operation.Independent predictors of OS were CA19-9 level(p=0.002),Child-Pugh score(p=0.027),tumor number(p=0.002),tumor size,and postoperative transhepatic arterial chemotherapy and embolization(TACE)(p=0.005).TACE can prolong postoperative recurrencefree survival.In the systemic therapy cohort,we collected the data of 34 patients who received first-line systemic therapy,21 patients received immunotherapy combined with targeted/chemotherapy,most of them were immunotherapy with lenvatinib(19 patients),11 patients only received targeted therapy,and 2 patients received chemotherapy alone(gemcitabine combined with paclitaxel/cisplatin),and these patients were divided into immunotherapy group(n=21)and the other group(n=13)according to whether they received immunotherapy.The overall objective response rate of these 34 patients was 23.5%(95%CI:11.4%-41.6%),the disease control rate was 58.8%(95%CI:40.8%-74.9%).Median overall survival(mOS)was 18.0 months(95%CI:12.4-NA),and the median progression-free survival(mPFS)was 6.0 months(95%CI:3.2-11.1).Compared with the other group,the mPFS of patients in the immunotherapy group was significantly prolonged(7.7m vs 3.2m,p=0.042),and the mOS also showed a trend of prolongation(21.3m vs 14.2m).Multivariate Cox analysis showed that the factor affecting OS was whether they had received local treatment before systemic treatment.Adverse events(AEs)occurred in all patients,and 48.5%of patients experienced grade 3-4 AEs.The most common AEs included hypertension(54.5%),decreased appetite(39.4%),fatigue(39.4%),rash(27.3%),hypoalbuminemia(27.3%),hand-foot syndrome(24.2%),and pain(21.2%).For the treatment of combined hepatocellular-cholangiocarcinoma,this study conducted a comprehensive exploration from the aspects of radical resection and systemic therapy.We studied the factors related to the prognosis and survival of surgical patients,and analyzed the efficacy and safety of first-line systemic therapy based on immunotherapy in unresectable combined hepatocellularcholangiocarcinoma patients for the first time.We found that immunotherapy combined with other therapy has good efficacy and safety in these patients,can significantly prolong the PFS,and improve the prognosis. |
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