Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach

Dear Editor,Hepatoid adenocarcinoma(HAC)is a rare pathological subtype of extrahepatic tumor,featured by hepatoid differentiation andα-fetoprotein(AFP)-production[1,2].Hepatoid adenocarcinoma of the stomach(HAS),accounting for 0.3%to 1.0%of all gastric cancers(GCs),has attracted increasing attention due to its high degree of malignancy[3].Compared with classic GC,HAS showed a higher rate of vascular invasion,lymph node metastasis,and liver metastasis,with only 9.0%survival rate at 5 years[4].Currently,there is no effective treatment for HAS,and little is known about its pathogenesis.Herein,we investigated the molecular features of HAS and identified potential therapeutic targets for HAS.

Toripalimab in advanced biliary tract cancer

Gemcitabine combined with platinum/fluorouracil drugs is the standard firstline treatment for advanced biliary tract cancers(BTCs).We explored the safety and efficacy of toripalimab plus gemcitabine and S-1(GS)as the first-line treatment for advanced BTCs.At a one-sided significance level of 0.025,a total of 50 patients could provide 80%power to show the efficacy at targeted progression-free survival(PFS)rate at 6 months of 70%versus 40%for the combined treatment.This single-arm,phase II study enrolled 50 patients with advanced BTCs who previously received no systemic treatment.The regimen was as follows:toripalimab(240 mg,i.v.,d1),gemcitabine(1,000 mg/m2,i.v.,d1 and d8),and S-1(40–60 mg bid p.o.,d1–14,Q21d).The primary endpoint was progression-free survival.The secondary endpoints included overall survival(OS),objective response rate(ORR),duration of response(DOR),and safety.The associations between response with PDL1 expression,tumor mutational burden(TMB),and genetic variations were explored.Patients were enrolled from January 2019 to August 2020,with a median follow-up time of 24.0 months(IQR:4.3–31.0 months).