Say‐Beng Tan

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 ( 90 Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

OBJECTIVE: To compare microvascular invasion (McVI) with parameters defined by the Milan criteria in predicting tumor recurrence and overall survival (OS) in patients with surgical resection (SR) for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Although the Milan criteria is discriminatory for selecting patients with good outcomes in liver transplantation and SR for HCC, it neither adequately predict tumor recurrence nor explain differences in survival for patients with good liver function. McVI is a strong indicator of intrahepatic metastasis in HCC, but its relative significance for predicting clinical outcomes compared to the Milan criteria is unclear. METHODS: Patients undergoing SR with curative intent from January 2000 to March 2009 at the Singapore General Hospital were followed up for long-term outcomes till January 1, 2010. They were stratified first by the Milan criteria and then by the presence of McVI and compared relative to OS. RESULTS: Altogether, 454 of the 515 patients received curative SR. There were stratified into 4 groups (Milan+, McVI-), (Milan+, McVI+), (Milan-, McVI-), and (Milan-, McVI+). All pair-wise comparisons between groups relative to OS were significant except (Milan+, McVI-) (OS, 90%, 73%, and 60% at 1, 3, and 5 years) with (Milan-, McVI-) (OS, 86%, 71%, and 61% at 1, 3, 5 years) and (Milan+, McVI+) with (Milan-, McVI+). Multivariate Cox regression analysis showed that McVI was predictive of OS, after which Milan status did not add additional discriminative information. CONCLUSIONS: McVI is a better predictor of tumor recurrence and OS than the Milan criteria after SR for HCC. Assessment of McVI should aid in patient selection for adjuvant treatments to improve outcomes after SR.

PURPOSE: To determine the risk factors of incident myopia in a school-based cohort study in Singaporean children. METHODS: A 3-year prospective cohort study was conducted in Singaporean school children aged 7 to 9 years in three schools at entry. Chinese children without myopia at baseline (n = 994) were included in the analysis. The main outcome was incident myopia, defined as spherical equivalent (SE) at least -0.75 D based on cycloplegic autorefraction. Other definitions of incident myopia, at least -0.5 D and at least -1.0 D, were also assessed. RESULTS: After controlling for school, age, gender, income, reading in books per week and intelligence quotient (IQ) test scores, we found the relative risk (RR) of incident myopia defined as -0.75 D to be 1.55 (95% confidence interval [CI] 1.18-2.04) for two versus no myopic parents. The multivariate RR of myopia for IQ in the third versus first tertile was 1.50 (95% CI, 1.19-1.89). However, the RR of incident myopia was 1.01 (95% CI, 0.97-1.05) for every unit increase in books read per week. Similar results were obtained with definitions of -0.5 and -1.0 D for incident myopia. CONCLUSIONS: These data provide new prospective evidence of essential links between parental myopia, IQ scores and subsequent myopia development. However, reading in books per week was not associated with incident myopia.

Purpose.: To describe and compare ocular component growth curves among different refractive error groups in Singaporean children. Methods.: Data collected yearly in 1775 Asian children aged 6 to 10 years with at least three visits were analyzed. Cycloplegic refractive error and biometry variables were measured by autorefractor and A-scan ultrasound machine. Growth curves were compared between five groups: persistent hyperopia of spherical equivalent (SE) > +1.00 D, emmetropizing hyperopia of SE > +1.00 D on the first visit and between −0.50 D and +1.00 D subsequently, persistent emmetropia of SE between −0.50 D and +1.00 D, incident myopia of SE ≤ −0.50 D at subsequent visits, and persistent myopia of SE ≤ −0.50 D. Results.: The axial length and vitreous chamber elongated faster in the children younger than 10 years, but elongation slowed with age. Growth patterns of axial length and vitreous chamber in the children with newly developed or persistent myopia (P < 0.01) showed faster elongation than in the emmetropic children. The anterior chamber deepened until approximately 9 or 10 years of age but became shallower as the myopic and emmetropic children grew older. Conversely, the lens thinned at younger ages and thickened at older ages for all except the persistently hyperopic children. Conclusions.: In young Asian children, the axial length and vitreous chamber depth increased, but the elongation slowed with age. There was a U-shaped growth curve for lens thickness and an inverted U-shaped curve for anterior chamber depth. The findings of early lens thinning followed by thickening suggest a two-phase growth of the lens.

PURPOSE: To evaluate the association between intelligence and myopia in children. METHODS: Cycloplegic refraction and ocular biometry parameters, including axial length, vitreous chamber depth, lens thickness, anterior chamber depth, and corneal curvature were obtained in 1204 Chinese school children aged 10 to 12 years from three schools who were participants in the Singapore Cohort Study Of the Risk Factors for Myopia (SCORM). Intelligence quotient (IQ) was assessed using the nonverbal Raven Standard Progressive Matrix test. RESULTS: After controlling for age, gender, school, parental myopia, father's education, and books read per week, myopia (spherical equivalent [SE]) of at least -0.5 D was associated with high nonverbal IQ (highest quartile) versus low IQ (lowest quartile) (odds ratio = 2.4; 95% confidence interval, 1.7-3.4). Controlling for the same factors, children with higher nonverbal IQ scores had significantly more myopic refractions (-1.86 D for children with nonverbal IQ in the highest quartile compared with -1.24 D for children with nonverbal IQ in the lowest quartile; P = 0.002) and longer axial lengths (24.06 mm versus 23.80 mm; P = 0.022). Nonverbal IQ accounted for a greater proportion of the variance in refraction compared with books read per week. CONCLUSIONS: Nonverbal IQ may be an independent risk factor of myopia, and this relationship may not be explained merely by increased reading (books per week) among myopes. An interesting observation is that nonverbal IQ may be a stronger risk factor for myopia compared with books read per week. The complexity of the relationships between nonverbal IQ, reading, and myopia warrant additional studies to clarify any cause-effect relationship.