Here, we report a case of postoperative recurrence of gallbladder carcinoma (GBC) in a patient who declined systemic chemotherapy. ATM S1905Ifs*25 and STK11 K262Sfs*25 mutations were detected by next-generation sequencing. Oral administration of olaparib was initiated. One month later, the patient experienced relief of clinical symptoms, a decrease in CA19-9 level, and a reduction in abnormal signal in the subcapsular region. The tumor response remained stable for approximately 13 months. This is the first case to demonstrate the clinical benefits of olaparib treatment in a patient with GBC harboring an ATM-inactivating mutation. This observation helps to better inform treatment options to enhance the care of patients with advanced GBC. The Oncologist 2020;25:375-379 KEY POINTS • A patient with gallbladder carcinoma harboring an ATM-inactivating mutation responded to olaparib with a progression-free survival of 13 months. • This is the first report that demonstrates the clinical benefits of olaparib treatment in a patient with gallbladder carcinoma with an ATM-inactivating mutation. • It also highlights the importance of next-generation sequencing, which can provide valuable information for planning effective targeted therapies for gallbladder carcinoma. • Evidence-based decisions help determine the best choice of treatment for individualized patient care.

Background and Objective: IDH1/2, BAP1, ARID1A and PBRM1 have been reported as the most frequent mutant genes in ICCs, and their relationships with clinicopathological features and prognosis were researched in this study.Methods: We collected clinical data of 130 ICC patients from January 2012 to December 2017. The IDH1/2 mutation and loss of BAP1, ARID1A and PBRM1 expressions were detected by DNA sequencing or IHC methods, and histological subtype of ICCs was determined by HE, Alcian blue and S100P staining.Results: IDH1/2 mutation was related to decreased TBIL (P=0.039), ferritin (P=0.000) and higher histological differentiation (P=0.024), and was associated with prolonged DFS (P=0.009) and a trend toward increased OS (P=0.126) in small duct type of ICCs. IHC result of MsMab-1 was generally consistent with DNA sequencing for IDH1/2 mutant in ICCs (κ= 0.691). Only BAP1 expression loss was correlated to prolonged DFS (P=0.031) and OS (P=0.041) in large duct type of ICCs.Conclusions: IDH1/2 mutation may be a favorable predictor and be related to iron metabolism in small duct type of ICCs. Furthermore, we suggest that the detection of IDH1/2 mutation is indispensable to determine targeted therapy in small duct of ICCs, while it is not necessary in large duct of ICCs. MsMab-1 was a relatively effective multi-specific antibody against IDH1/2 mutant in ICCs. BAP1 expression loss was related to an improved prognosis in large duct type of ICCs.

No abstract

Background: Isocitrate dehydrogenase 1/2 (IDH1/2), BAP1, ARID1A and PBRM1 have been reported as the most frequent mutant genes in intrahepatic cholangiocarcinoma (ICC), and their relationships with clinicopathological features and prognosis were researched in this study. Methods: We collected clinical data of 130 ICC patients from January 2012 to December 2017. The IDH1/2 mutation and loss of BAP1, ARID1A and PBRM1 expressions were detected by DNA sequencing or immunohistochemical methods, and histological subtype of ICCs was determined by hematoxylin-eosin, Alcian blue and S100P staining. Results: IDH1/2 mutation was related to decreased preoperative serum total bilirubin (P=0.039), ferritin (P=0.000) and higher histological differentiation (P=0.024), and was associated with prolonged disease-free surviva l (P=0.009) and a trend toward increased overall survival (P=0.126) in small duct type of ICCs. Immunohistochemical staining results of MsMab-1 were generally consistent with DNA sequencing for IDH1/2 mutant in ICCs (κ= 0.691). Only BAP1 expression loss was correlated to prolonged disease-free survival (P=0.031) and overall survival (P=0.041) in large duct type of ICCs. Conclusions : IDH1/2 mutation is a favorable predictor and may be related to iron metabolism in small duct type of ICCs. Furthermore, we suggest that the detection of IDH1/2 mutation is indispensable to determine targeted therapy in small duct type ICCs, while it is not necessary in large duct of ICCs. MsMab-1 is a relatively effective multi-specific antibody against IDH1/2 mutant in ICCs. BAP1 expression loss was correlated with improved prognosis only in large duct type ICCs.