H epatocellular carcinoma (HCC) is the sixth leading type of cancer and the second most fatal tumor worldwide (1). For patients with early stage HCC as defined by the Milan criteria (solitary nodule 5 cm or as many as three nodules 3 cm, without macrovascular invasion and extrahepatic spread), both liver resection and liver transplant are the mainstay curative options (1,2). Although liver transplant offers definite advantages of extirpating both the tumor and the diseased liver, demand for organs far exceeds supply. Therefore, liver resection is accepted as the first-line treatment option for patients with early stage HCC and preserved liver function, whereas liver transplant is the recommended treatment for patients with decompensated cirrhosis (3). Unfortunately, HCC recurrence, including true recurrence by means of tumor dissemination and development of de novo tumors in the cirrhotic liver, occurs in 50%-60% of these patients at 5 years (4,5).Currently, HCC staging systems (eg, Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, Cancer of the Liver Italian Program, and TNM systems) occupy the central role in prognosis and therefore treatment allocation (1). Accurate risk prediction allows optimal surveillance, prevention, and management strategies for tumor recurrence; however, these systems are inadequate for predicting recurrence, and none of them provide quantifiable risk measures. Recently, a few statistical models, such as the Korean model ( 6) and pre-and postoperative Early Recurrence After Surgery for Liver Tumor (ERASL) models ( 7), have been established specifically to predict HCC
BackgroundImmune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response.MethodsIn this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m2) and oxaliplatin (85 mg/m2). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment.Results54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS <1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p>0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28).ConclusionCamrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX.Trial registration numberNCT03486678.
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