Data guiding selection of nonsurgical treatment of hepatocellular carcinoma (HCC) are lacking. We therefore compared outcomes between stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) for HCC. Patients and MethodsFrom 2004 to 2012, 224 patients with inoperable, nonmetastatic HCC underwent RFA (n = 161) to 249 tumors or image-guided SBRT (n = 63) to 83 tumors. We applied inverse probability of treatment weighting to adjust for imbalances in treatment assignment. Freedom from local progression (FFLP) and toxicity were retrospectively analyzed.Results RFA and SBRT groups were similar with respect to number of lesions treated per patient, type of underlying liver disease, and tumor size (median, 1.8 v 2.2 cm in maximum diameter; P = .14). However, the SBRT group had lower pretreatment Child-Pugh scores (P = .003), higher pretreatment alpha-fetoprotein levels (P = .04), and a greater number of prior liver-directed treatments (P , .001). One-and 2-year FFLP for tumors treated with RFA were 83.6% and 80.2% v 97.4% and 83.8% for SBRT. Increasing tumor size predicted for FFLP in patients treated with RFA (hazard ratio [HR], 1.54 per cm; P = .006), but not with SBRT (HR, 1.21 per cm; P = .617). For tumors $ 2 cm, there was decreased FFLP for RFA compared with SBRT (HR, 3.35; P = .025). Acute grade 3+ complications occurred after 11% and 5% of RFA and SBRT treatments, respectively (P = .31). Overall survival 1 and 2 years after treatment was 70% and 53% after RFA and 74% and 46% after SBRT. ConclusionBoth RFA and SBRT are effective local treatment options for inoperable HCC. Although these data are retrospective, SBRT appears to be a reasonable first-line treatment of inoperable, larger HCC.

IMPORTANCE Black men are more likely to die of prostate cancer than white men. In men with similar stages of disease, the contribution of biological vs nonbiological differences to this observed disparity is unclear. OBJECTIVE To quantify the association of black race with long-term survival outcomes after controlling for known prognostic variables and access to care among men with prostate cancer. DESIGN, SETTING, AND PARTICIPANTS This multiple-cohort study included updated individual patient-level data of men with clinical T1-4N0-1M0 prostate cancer from the following 3 cohorts: Surveillance, Epidemiology, and End Results (SEER [n = 296 273]); 5 equal-access regional medical centers within the Veterans Affairs health system (VA [n = 3972]); and 4 pooled National Cancer Institute-sponsored Radiation Therapy Oncology Group phase 3 randomized clinical trials (RCTs [n = 5854]). Data were collected in the 3

Purpose Radiation therapy is a critical component in the care of patients with non–small-cell lung cancer (NSCLC), yet cardiac injury after treatment is a significant concern. Therefore, we wished to elucidate the incidence of cardiac events and their relationship to radiation dose to the heart. Patients and Materials Study eligibility criteria included patients with stage II to III NSCLC treated on one of four prospective radiation therapy trials at two centers from 2004 to 2013. All cardiac events were reviewed and graded per Common Terminology Criteria for Adverse Events (v4.03). The primary end point was the development of a grade ≥ 3 cardiac event. Results In all, 125 patients met eligibility criteria; median follow-up was 51 months for surviving patients. Median prescription dose was 70 Gy, 84% received concurrent chemotherapy, and 27% had pre-existing cardiac disease. Nineteen patients had a grade ≥ 3 cardiac event at a median of 11 months (interquartile range, 6 to 24 months), and 24-month cumulative incidence was 11% (95% CI, 5% to 16%). On multivariable analysis (MVA), pre-existing cardiac disease (hazard ratio [HR], 2.96; 95% CI, 1.07 to 8.21; P = .04) and mean heart dose (HR, 1.07/Gy; 95% CI, 1.02 to 1.13/Gy; P = .01) were significantly associated with grade ≥ 3 cardiac events. Analyzed as time-dependent variables on MVA analysis, both disease progression (HR, 2.15; 95% CI, 1.54 to 3.00) and grade ≥ 3 cardiac events (HR, 1.76; 95% CI, 1.04 to 2.99) were associated with decreased overall survival. However, disease progression (n = 71) was more common than grade ≥ 3 cardiac events (n = 19). Conclusion The 24-month cumulative incidence of grade ≥ 3 cardiac events exceeded 10% among patients with locally advanced NSCLC treated with definitive radiation. Pre-existing cardiac disease and higher mean heart dose were significantly associated with higher cardiac event rates. Caution should be used with cardiac dose to minimize risk of radiation-associated injury. However, cardiac risks should be balanced against tumor control, given the unfavorable prognosis associated with disease progression.

The first formal qualification of safety biomarkers for regulatory decision making marks a milestone in the application of biomarkers to drug development. Following submission of drug toxicity studies and analyses of biomarker performance to the Food and Drug Administration (FDA) and European Medicines Agency (EMEA) by the Predictive Safety Testing Consortium's (PSTC) Nephrotoxicity Working Group, seven renal safety biomarkers have been qualified for limited use in nonclinical and clinical drug development to help guide safety assessments. This was a pilot process, and the experience gained will both facilitate better understanding of how the qualification process will probably evolve and clarify the minimal requirements necessary to evaluate the performance of biomarkers of organ injury within specific contexts.

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Background Improved clinical predictors for disease progression are needed for localized prostate cancer, where only a minority of patients experience poor outcomes. We undertake an unbiased large-scale analysis of genes associated with aggressive clinical course. Methods Prostate cancer samples, obtained from patients treated with radical prostatectomy at three academic institutions, were analyzed for gene expression using a clinical-grade, high-density Affymetrix GeneChip platform, encompassing >1 million genomic loci. Nomination of prognostic candidate genes was performed on a discovery cohort (n=545) and validated on three independent cohorts (n=463), totaling 1,008 patients. Molecular assays were performed in a CLIA-certified (Clinical Laboratory Improvement Amendments) laboratory facility. Multivariate analyses were performed for the primary endpoint of metastasis. The top prostate-specific gene was evaluated in urine samples from 230 patients using PCR. Findings Among all known genes, the long noncoding RNA SChLAP1 ranked first for elevated expression in patients with metastatic progression by receiver-operator-curve (ROC) area-under-the-curve (AUC) analyses. Of the top five prognostic genes, SChLAP1 was the only prostate-specific gene. Validation in three independent cohorts confirmed the prognostic value of SChLAP1 for metastasis. On multivariate modeling, SChLAP1 expression independently predicted metastasis within ten years (odds ratio (OR) = 2·45, 95% confidence interval (CI) 1·70 – 3·53), death within ten years (OR = 1·93, 95% CI 1·31 – 2·85), and biochemical recurrence within five years (OR = 1·76, 95% CI 1·28 – 2·41) with odds ratios comparable to Gleason score. Evaluation of SChLAP1 expression in 230 urine sediment samples with either biopsy-confirmed cancer or biopsy-negative tissue demonstrated increased incidence and expression of SChLAP1 RNA in patients at a higher risk for disease progression. Interpretation We perform the largest high-throughput, unbiased study of prostate cancer prognostic biomarkers to date and discover SChLAP1 as one of the best genes for the prediction of metastasis. We validate SChLAP1 extensively using a clinical-grade assay in a CLIA-certified laboratory. We show feasibility of a non-invasive urine test for SChLAP1, and suggest that SChLAP1 represents a very promising biomarker for aggressive clinical course. Funding Prostate Cancer Foundation, National Institutes of Health, Department of Defense, Early Detection Research Network, Doris Duke Charitable Foundation, and Howard Hughes Medical Institute.

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Background Concurrent chemoradiotherapy (concurrent CRT) to treat head and neck cancer is associated with significant reductions of weight, mobility, and quality of life (QOL). An intervention focusing on functional exercise may attenuate these losses. Methods We allocated patients to a 14-week functional resistance and walking program designed to maintain physical activity during cancer treatment (MPACT group; n = 11), or to usual care (control group; n = 9). Outcomes were assessed at baseline, and 7 and 14 weeks. Results Compared to controls, the MPACT participants had attenuated decline or improvement in several strength, mobility, physical activity, diet, and QOL endpoints. These trends were statistically significant (p < .05) in knee strength, mental health, head and neck QOL, and barriers to exercise. Conclusion In this pilot study of patients with head and neck cancer undergoing concurrent CRT, MPACT training was feasible and maintained or improved function and QOL, thereby providing the basis for larger future interventions with longer follow-up.