IMPORTANCE Indoor tanning is a known carcinogen, but the scope of exposure to this hazard is not known. OBJECTIVE To summarize the international prevalence of exposure to indoor tanning. DATA SOURCES Studies were identified through systematic searches of PubMed (1966 to present), Scopus (1823 to present), and Web of Science (1898 to present) databases, last performed on March 16, 2013. We also hand searched reference lists to identify records missed by database searches and publicly available data not yet published in the scientific literature. STUDY SELECTION Records reporting a prevalence of indoor tanning were eligible for inclusion. We excluded case-control studies, reports with insufficient study information, and reports of groups recruited using factors related to indoor tanning. Two independent investigators performed searches and study selection. Our search yielded 1976 unique records. After exclusions, 161 records were assessed for eligibility in full text, and 88 were included. DATA EXTRACTION AND SYNTHESIS Two independent investigators extracted data on characteristics of study participants, inclusion/exclusion criteria, data collection format, outcomes, and statistical methods. Random-effects meta-analyses were used to summarize the prevalence of indoor tanning in different age categories. We calculated the population proportional attributable risk of indoor tanning in the United States, Europe, and Australia for nonmelanoma skin cancer (NMSC) and melanoma. MAIN OUTCOMES AND MEASURES Ever and past-year exposure to indoor tanning. RESULTS The summary prevalence of ever exposure was 35.7% (95% CI, 27.5%-44.0%) for adults, 55.0% (33.0%-77.1%) for university students, and 19.3% (14.7%-24.0%) for adolescents. The summary prevalence of past-year exposure was 14.0% (95% CI, 11.5%-16.5%) for adults, 43.1% (21.7%-64.5%) for university students, and 18.3% (12.6%-24.0%) for adolescents. These results included data from 406 696 participants. The population proportional attributable risk were 3.0% to 21.8% for NMSC and 2.6% to 9.4% for melanoma, corresponding to more than 450 000 NMSC cases and more than 10 000 melanoma cases each year attributable to indoor tanning in the United States, Europe, and Australia. CONCLUSIONS AND RELEVANCE Exposure to indoor tanning is common in Western countries, especially among young persons. Given the large number of skin cancer cases attributable to indoor tanning, these findings highlight a major public health issue.

We retrospectively analyzed non-small cell lung cancer (NSCLC) patients from a single center treated with pembrolizumab on the KEYNOTE-001 trial and evaluated the association between treatment-related adverse events (trAEs) and clinical outcomes. Investigators reported AEs on trial and graded them according to Common Terminology Criteria for Adverse Events v4.0, labeling them as unlikely, possibly, or probably treatment-related. AEs labeled as possibly/probably related were considered trAEs for this analysis. The relationship between the incidence of a trAE and clinical outcomes was evaluated. Ninety-seven NSCLC patients treated on KEYNOTE-001 at the University of California, Los Angeles were evaluated. Ten percent (85/826) of AEs were trAEs, occurring in 40% (39/97) of patients. The most frequent trAEs were rash (21% patients), fatigue (6% patients), and hypothyroidism (6% patients). The 39 patients that experienced a trAE had increased objective response rate (ORR, 38.5%), progression-free survival (PFS: median, 248 days), and overall survival (OS: median, 493 days), compared with the 58 patients that did not (ORR: 8.9%, PFS: median 60 days, OS: median 144.5 days). The observed association between trAEs and improved clinical outcome persisted when using Cox proportional hazards regression models to assess the confounding effect of covariates and mitigate guarantee-time bias. The association also remained when data were substratified by grade, degree of association, and treatment-related select AE designation. This single-center analysis revealed that trAEs predicted for improved clinical outcome with pembrolizumab, and when controlling for guarantee-time bias and plausible confounders, this association remained. This observed relationship adds to our understanding of anti-PD-1 therapy and could aid clinicians in identifying patients most likely to benefit from therapy.

Background Clinical trials in lung cancer increasingly require subjects to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and subject selection have not been fully elucidated. Methods We retrospectively reviewed data generated by patients who consented to one or more interventional lung cancer clinical trials the UCLA Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment. Results: 311 patients underwent 368 screening incidents for one or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs. 14 days) than trials that did not require a biopsy (p<0.001). Trials requiring a biopsy had a greater screen failure rate (49.1% v. 26.5%, p<0.001), largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker-eligible patients. Conclusions: Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, it leads to a lengthening of the screening period, which, in some cases, is associated with clinical decline prior to enrollment. Implications for the interpretation of data from studies of this design should be explored.

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Lung cancer is the leading cause of cancer mortality. Great advances in non-small cell lung cancer therapy have been seen in the last decade, beginning with the success in treating lung cancer harboring EGFR mutations and ALK-gene rearrangements. The potential of these biomarker-driven therapies has propelled research in biomarker targeted approaches to the forefront of lung cancer research. The successful development of immunotherapeutic agents targeting PD-L1 and PD-1 with an associated non-genomic biomarker has opened a new front in the effort for targeted approaches. Although early-phase lung cancer studies have hinted at the potential to use biomarkers to select patients for allocation to treatment in the conduct of clinical trials, data from late-phase studies have tempered expectations. The data leave unclear the wisdom of routinely restricting enrollment on lung cancer clinical trials to biomarker restricted populations, particularly non-genomic biomarkers.

<p>Table S3: The occurrence of a treatment related AE (trAE) in the 97 patients treated at UCLA on the KEYNOTE-001 clinical trial, stratified by a history of thoracic radiation therapy (TRT) or prior radiation therapy to any location. P values computed via Fisher's exact test.</p>

<p>Table S1: All adverse events occurring in > 5% of patients in the UCLA NSCLC cohort of 97 patients treated on KEYNOTE-001.</p>

<p>Supplementary Table S5a: Cox proportional hazards models for progression-free survival (PFS) with number of treatment related select adverse events included as a time-varying covariate. Listed are results from both unadjusted models and adjusted models. Hazard ratio estimates marked '(+1)' correspond to the incremental effect of a unit increase in the relevant predictor.</p>