PURPOSE Patients with centrally located early-stage non–small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS Medically inoperable patients with biopsy-proven, positron emission tomography–staged T1 to 2 (≤ 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. RESULTS One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively. CONCLUSION The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.

Purpose/Objective(s): To present long-term results of RTOG 0915/NCCTG N0927, a randomized lung stereotactic body radiotherapy (SBRT) trial of 34 Gy in 1 fraction versus 48 Gy in 4 fractions. Materials/Methods: This was a phase II multicenter study of medically inoperable non-small cell lung cancer patients with biopsy-proven peripheral T1 or T2 N0M0 tumors, with 1-year toxicity rates as primary endpoint and selected failure and survival outcomes as secondary endpoints. The study opened in September 2009 and closed in March 2011. Final data were analyzed through May 17, 2018. Results: Eighty four of 94 patients accrued were eligible for analysis: 39 in arm 1 and 45 in arm 2. Median follow-up time was 4.0 years for all patients, and 6.0 years for those alive at analysis. Rates of grade 3 and higher toxicity were 2.6% in arm 1 and 11.1% in arm 2. Median survival times (in years) for 34 Gy and 48 Gy were 4.1 vs. 4.6, respectively. Five-year outcomes as % (95% CI) for 34 Gy and 48 Gy were: primary tumor failure rate of 10.6 (3.3, 23.1) vs. 6.8 (1.7, 16.9); overall survival of 29.6 (16.2, 44.4) vs. 41.1 (26.6, 55.1); and progression-free survival of 19.1 (8.5, 33.0) vs. 33.3 (20.2, 47.0); respectively. Distant failure as the sole failure or a component of first failure occurred in 6 patients (37.5%) in the 34 Gy arm and in 7 (41.2%) in the 48 Gy arm. Conclusions: No excess in late-appearing toxicity was seen in either arm. Primary tumor control rates at 5 years were similar by arm. Median survival times of 4 years for each arm suggest similar efficacy pending any larger studies appropriately powered to detect survival differences.

Purpose The purpose of this paper is to comprehensively analyze the corporate social responsibility (CSR) and sustainability reporting (SR) practices of Indian companies in terms of disclosure quantity and quality, and to investigate the differences in SR practices by SR dimension, industry, ownership structure, firm size and profitability. Design/methodology/approach Data are collected from annual reports/business responsibility reports (BRR)/CSR/sustainability reports of 60 top-listed companies in India. A comprehensive sustainability reporting index is developed. Content analysis technique is used. Inter-coder reliability is established. Findings Altogether, 18 items of the index are not disclosed by the majority of companies in India. SR quality is found significantly lower than the SR quantity. Moreover, SR practices significantly differ by dimension/category, industry-type and firm-size but are not influenced by ownership structure. However, the study fails to establish any conclusive relationship between SR and profitability. Practical implications The present study has several implications for corporates, practitioners, policymakers and stakeholders. The findings underscore the need for amendments in the Global Reporting Initiative guidelines and BRR framework of the Securities and Exchange Board of India to avoid patchy disclosures and ensure complete reporting by companies. Originality/value This study is among the foremost studies in India evaluating SR practices of top-listed companies in the wake of the mandatory BRR requirement from a quantitative as well as qualitative perspective using a multidimensional index.

Nanotoxicology and nanosafety has been a topic of intensive research for about more than 20 years. Nearly 10 000 research papers have been published on the topic, yet there exists a gap in terms of understanding and ways to harmonize nanorisk assessment. In this review, we revisit critically ignored parameters of nanoscale materials (e.g. band gap factor, phase instability and silver leaching problem, defect and instability plasmonic versus inorganic particles) versus their biological counterparts (cell batch-to-batch heterogeneity, biological barrier model design, cellular functional characteristics) which yield variability and nonuniformity in results. We also emphasize system biology approaches to integrate the high throughput screening methods coupled with in vivo and in silico modeling to ensure quality in nanosafety research. We emphasize and highlight the recommendation regarding bridging the mechanistic gaps in fundamental research and predictive biological response in nanotoxicology. The research community has to develop visions to predict the unforeseen problems that do not exist yet in context with nanotoxicity and public health hazards due to the burgeoning use of nanomaterial in consumer's product. ARTICLE HISTORY

Aims Metformin could have benefits on cardiovascular disease and kidney disease progression but is often withheld from individuals with diabetes and chronic kidney disease (CKD) because of a concern that it may increase the risk of lactic acidosis. Materials and methods All‐cause mortality, cardiovascular death, cardiovascular events (death, hospitalization for heart failure, myocardial infarction, stroke or myocardial ischemia), end stage renal disease (ESRD) and the kidney disease composite (ESRD or death) were compared in metformin users and non‐users with diabetes and CKD enrolled in the Trial to Reduce Cardiovascular Events with Aranesp (darbepoeitin‐alfa) Therapy (TREAT) (NCT00093015). Outcomes were compared after propensity matching of users and non‐users and in multivariable proportional hazards models. Results There were 591 individuals who used metformin at baseline and 3447 non‐users. Among propensity‐matched users, the crude incidence rate for mortality, cardiovascular mortality, cardiovascular events and the combined endpoint was lower in metformin users than in non‐users, but ESRD was marginally higher (4.0% vs 3.6%). Metformin use was independently associated with a reduced risk of all‐cause mortality (HR, 0.49; 95% CI, 0.36‐0.69), cardiovascular death (HR, 0.49; 95% CI, 0.32‐0.74), the cardiovascular composite (HR, 0.67, 95% CI, 0.51‐0.88) and the kidney disease composite (HR, 0.77; 95% CI, 0.61‐0.98). Associations with ESRD (HR, 1.01; 95% CI, 0.65‐1.55) were not significant. Results were qualitatively similar in adjusted analyses of the full population. Two cases of lactic acidosis were observed. Conclusions Metformin may be safer for use in CKD than previously considered and may lower the risk of death and cardiovascular events in individuals with stage 3 CKD.