Screening for hepatocellular carcinoma (HCC) is clinically important given that its early detection has remarkable survival benefits. We investigated the possible role of FIB-4, a recently developed noninvasive marker for liver fibrosis based on routine laboratory tests, as a clinical indicator for predicting future HCC among hepatitis B surface antigen (HBsAg) carriers. Our retrospective cohort study involved 986 Korean HBsAg carriers 40 years of age or older who visited Seoul National University Hospital for a health checkup. National medical service claims data were used to determine HCC incidence. Median follow-up time was 5.4 years (interquartile range: 4.4 years). Adjusted for age, sex, body mass index, smoking, alcohol, and antiviral medication for hepatitis B, compared to subjects with FIB-4 <1.25, subjects with 1.7 £ FIB-4 <2.4 showed an adjusted hazard ratio (aHR) of 4.57 (95% confidence interval [CI]: 1.50-13.92) and subjects with FIB-4 2.4 showed an aHR of 21.34 (95% CI: 7.73-58.92) for HCC incidence. FIB-4 was shown to have incremental predictive value to ultrasonographic liver cirrhosis for HCC incidence (C-index: 0.701 vs. 0.831; P 5 0.001). FIB-4 was also better predictive of HCC incidence, compared to that of ultrasonographic liver cirrhosis (C-index: 0.775 vs. 0.701; P 5 0.040). Conclusion: High FIB-4 is a highly predictive risk factor for HCC incidence among Korean HBsAg carriers. FIB-4 is a promising, easily applicable, and cost-effective clinical tool in identifying a subpopulation of HBsAg carriers who are at heightened risk. Our study needs to be replicated in larger future studies on various ethnic groups; nonetheless, our study suggests that FIB-4 may play a valuable role in HCC screening among HBsAg carriers. (HEPATOLOGY 2015;61:1261-1268 L iver cancer is the fifth-most frequently diagnosed cancer worldwide in men, also the secondleading cause of cancer mortality in the world. 1 For females, it is the seventh-most common cancer and sixth-leading cause of cancer mortality. 1 Liver cancer incidence is increasing in many parts of the world, including in the United States and Europe. 2,3 In Korea, liver cancer represents the second-highest cause of cancer mortality and is the fifth-most frequently diagnosed cancer. 4 Despite such high incidence and mortality, major risk factors for liver cancer are well established as chronic hepatitis and cirrhosis, 5 similarly in Korea where liver cancer has been attributed to chronic hepatitis B (CHB), C, or cirrhosis in 95% of

ROS1-positive NSCLC has distinct clinical characteristics, with an effective and durable response to both TKIs and pemetrexed-based chemotherapies. Regardless, given its novel characteristics and distinct clinical responses to conventional chemotherapies and TKIs, the treatment strategy for ROS1-positive NSCLC remains to be further developed.

Introduction: Impairment in DNA damage response and repair (DDR) pathway is known as a predictive biomarker of platinum sensitivity. Recently, DDR alteration is reemphasized as a predictive biomarker of immune checkpoint inhibitor due to its positive correlation to tumor mutation burden (TMB). Methods: Target gene sequencing (381 genes) was conducted from 100 extensive disease (ED) and 66 limited disease (LD) patients with SCLC. Detected mutations were classified as double-strand breaks (DSB) (n ¼ 82): homologous recombination (n ¼ 54), non-homologous end joining (n ¼ 19), and Fanconi anemia (n ¼ 32); or singlestrand breaks (SSB) (n ¼ 31): mismatch repair (n ¼ 19), base excision repair (n ¼ 7), and nucleotide excision repair (n ¼ 6). Results: Compared to patients with an intact DDR pathway (n ¼ 70), a higher TMB was observed in patients with homologous recombination (p < 0.001), non-homologous end joining (p ¼ 0.002), mismatch repair (p < 0.001), DSB (p < 0.001), and SSB (p < 0.001). Survival analyses based on TMB level showed no predictive or prognostic values in ED patients. In LD patients, prolonged progression-free survival (hazard ratio [HR] ¼ 0.497, p ¼ 0.015), and overall survival (HR ¼ 0.383, p ¼ 0.010) to concurrent chemoradiotherapy were observed in those with TMB above median. Individual DDR pathway alteration showed no survival benefit in ED patients receiving platinum-based chemotherapy. In LD patients, those with mutations in the Fanconi anemia gene set had shorter progression-free survival (HR ¼ 2.048, p ¼ 0.036) to initial treatment. Conclusions: DDR pathway alterations, both DSB and SSB, in SCLC have a positive correlation with high TMB. However, it has shown limited value in prediction of platinum efficacy.