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Purpose Use of stereotactic ablative radiation therapy (SABR) for subcentimeter lung tumors is controversial. We report our outcomes for tumors with diameter ≤1 cm and their visibility on cone beam computed tomography (CBCT) scans and retrospectively evaluate the planned dose using a deterministic dose calculation algorithm (Acuros XB [AXB]). Methods and Materials We identified subcentimeter tumors from our institutional SABR database. Tumor size was remeasured on an artifact-free phase of the planning 4-dimensional (4D)-CT. Clinical plan doses were generated using either a pencil beam convolution or an anisotropic analytic algorithm (AAA). All AAA plans were recalculated using AXB, and differences among D95 and mean dose for internal target volume (ITV) and planning target volume (PTV) on the average intensity CT dataset, as well as for gross tumor volume (GTV) on the end respiratory phases were reported. For all AAA patients, CBCT scans acquired during each treatment fraction were evaluated for target visibility. Progression-free and overall survival rates were calculated using the Kaplan-Meier method. Results Thirty-five patients with 37 subcentimeter tumors were eligible for analysis. For the 22 AAA plans recalculated using AXB, Mean D95 ± SD values were 2.2 ± 4.4% (ITV) and 2.5 ± 4.8% (PTV) lower using AXB; whereas mean doses were 2.9 ± 4.9% (ITV) and 3.7 ± 5.1% (PTV) lower. Calculated AXB doses were significantly lower in one patient (difference in mean ITV and PTV doses, as well as in mean ITV and PTV D95 ranged from 22%-24%). However, the end respiratory phase GTV received at least 95% of the prescription dose. Review of 92 CBCT scans from all AAA patients revealed that the tumor was visualized in 82 images, and its position could be inferred in other images. The 2-year local progression-free survival was 100%. Conclusions Patients with subcentimeter lung tumors are good candidates for SABR, given the dosimetry, ability to localize tumors with image guidance, and excellent local control.

Purpose The clinical benefits and risks of dose escalation (DE) for stage III non–small-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74 Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database. Methods and Materials An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2 groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy ≤ BED 10 ≤ 76.8 Gy (eg 60-64 Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy 64 Gy/32 fr and Results Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89 months; ID were 40 months). Median dose fractionation was 60 Gy/30 fr in SD (BED 10 IQR: 72.0-75.5 Gy) and 66 Gy/33 fr (BED 10 IQR: 78.6-79.2 Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar ( P =.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15 months (median survival SD: 19.3 months; ID: 21.0 months). There was an increase in grades III to V lung toxicity associated with ID (13.0% vs 4.9%, respectively). Conclusions No significant overall survival benefits were found with intermediate DE; however, more grade III or greater lung toxicity was observed. The separation of survival curves after 15 months of follow-up suggests that a small overall survival improvement associated with intermediate DE cannot be excluded.

Summary Cancer is a substantial health burden for Inuit populations, an Indigenous peoples who primarily inhabit the circumpolar regions of Alaska, Canada, Greenland, and Russia. Access to radiotherapy is lacking or absent in many of these regions, despite it being an essential component of cancer treatment. This Review presents an overview of factors influencing radiotherapy delivery in each of the four circumpolar Inuit regions, which include population and geography, health-systems infrastructure, and cancer epidemiology. This Review also provides insight into the complex patient pathways needed to access radiotherapy, and on radiotherapy use. The unique challenges in delivering radiotherapy to circumpolar Inuit populations are discussed, which, notably, include geographical and cultural barriers. Recommendations include models of care that have successfully addressed these barriers, and highlight the need for increased collaboration between circumpolar referral centres in Alaska, Canada, Greenland, and Russia to ultimately allow for better delivery of cancer treatment.

Thoracic radiotherapy (TRT) has been evaluated as a means of improving overall survival and progression-free survival in patients with extensive stage small-cell lung cancer (ES-SCLC).A systematic review of Medline and Embase (inception to January 2015) was undertaken to identify studies of extensive stage SCLC patients receiving platinum-based chemotherapy and randomized to receive TRT versus no TRT. Studies were screened by title (n = 2343) and then abstract (n = 72), with subsequent full-text review (n = 16). Effect estimates (hazard ratios [HR] and confidence intervals) were abstracted, with a random-effects model created to estimate treatment effects. Cochrane's Q and I(2) statistics were used to assess study heterogeneity.Two randomized studies were identified, including a total of 604 patients (302 TRT; 302 non-TRT). All patients received prophylactic cranial irradiation. The weighted median age was 62 years, and 56% were male. TRT was delivered as 30 Gy/10 fractions (n = 247) or 54 Gy twice daily/36 fractions (n = 55). Overall, the delivery of TRT was associated with improved overall survival (HR, 0.81; 95% confidence interval, 0.69-0.96; P = .014) and progression-free survival (HR, 0.74; 95% confidence interval, 0.64-0.87, P .001). For both end points, the studies were not found to be heterogeneous (P = .439 and P = .638 respectively, I(2) = 0). Bronchopulmonary toxicity (grade 3 or higher) was similar in both groups (≤ 2%). Esophageal toxicity (grade 3 or higher) was 6.6% in the TRT arm and 0% in the non-TRT arm (P .001).This systematic review with meta-analysis of 2 randomized trials indicates that TRT improves overall survival and progression-free survival in patients with extensive stage SCLC, with a small incremental risk of esophageal toxicity.

Background Most methodologists recommend intention-to-treat (ITT) analysis in order to minimize bias. Although ITT analysis provides an unbiased estimate for the effect of treatment assignment on the outcome, the estimate is biased for the actual effect of receiving treatment (active treatment) compared to some comparison group (control). Other common analyses include measuring effects in (1) participants who follow their assigned treatment (Per Protocol), (2) participants according to treatment received (As Treated), and (3) those who would comply with recommended treatment (Complier Average Causal Effect (CACE) as estimated by Principal Stratification or Instrumental Variable Analyses). As each of these analyses compares different study subpopulations, they address different research questions. Purpose For each type of analysis, we review and explain (1) the terminology being used, (2) the main underlying concepts, (3) the questions that are answered and whether the method provides valid causal estimates, and (4) the situations when the analysis should be conducted. Methods We first review the major concepts in relation to four nuances of the clinical question, ‘Does treatment improve health?’ After reviewing these concepts, we compare the results of the different analyses using data from two published randomized controlled trials (RCTs). Each analysis has particular underlying assumptions and all require dichotomizing adherence into Yes or No. We apply sensitivity analyses so that intermediate adherence is considered (1) as adherence and (2) as non-adherence. Results The ITT approach provides an unbiased estimate for how active treatment will improve (1) health in the population if a policy or program is enacted or (2) health of patients if a clinician changes treatment practice. The CACE approach generally provides an unbiased estimate of the effect of active treatment on health of patients who would follow the clinician’s advice to take active treatment. Unfortunately, there is no current analysis for clinicians and patients who want to know whether active treatment will improve the patient’s health if taken, which is different from the effect in patients who would follow the clinician’s advice to take active treatment. Sensitivity analysis for the CACE using two published data sets suggests that the underlying assumptions appeared to be violated. Limitations There are several methods within each analytical approach we describe. Our analyses are based on a subset of these approaches. Conclusions Although adherence-based analyses may provide meaningful information, the analytical method should match the clinical question, and investigators should clearly outline why they believe assumptions hold and should provide empirical tests of the assumptions where possible.

Abstract Purpose The quality of stereotactic body radiation therapy (SBRT) treatment plans for early stage lung cancer are unknown outside of peer-reviewed publications. Thus, a study was conducted to crowdsource and analyze a variety of lung SBRT treatment plans from around the world. Methods and Materials This study had 2 parts, planning and contouring, and each was facilitated by a web-based technology platform. For planning, lung SBRT planners were invited to design, score, and submit their treatment plans (prescription of 11 Gy × 5) for a centralized stage I lung cancer case using standardized images and predefined contours. Each plan was scored with 20 weighted metrics adapted from currently recruiting phase 3 lung SBRT trials. For contouring, a separate image set was used to evaluate organ-at-risk contour accuracy using Dice coefficients and a StructSure score. Results For planning 227 plans were submitted in total with 7 different treatment planning systems and 7 different delivery methods represented. Variability was primarily user driven and not associated with the treatment planning system, delivery modality, total monitor units, or estimated beam-on time. Many of the highest-quality plans required the shortest amount of time to deliver, independent of the delivery technique. For contouring, organ-at-risk contours were frequently over- or undercontoured and often included only the luminal air of the trachea, proximal bronchial tree, and esophagus, even when the mucosal linings were within a few centimeters of the target tumor. Conclusions These findings demonstrate the importance of quality assurance to help improve planning and contouring and the value of peer review and comparison. More readily accessible quality evaluation software solutions, such as the one used herein, may help meet this growing need.

Quenched-flow data for propene polymerization with rac-Me2Si(2-Me-4-Ph-1-indenyl)(2)ZrCl2/MAO support a picture where removal of MAO qualitatively changes the kinetic profile from a mainly enthalpic to a mainly entropic barrier. DFT studies suggest that a not previously recognized singly-bridged end-on coordination mode of Me6Al2 to catalytically active centers may be kinetically relevant as a resting state. In contrast, the more traditional doubly-bridged complex of Me3Al is proposed to be more relevant to chain transfer to cocatalyst.

A decade ago, Blair1 pondered the future of physical activity research, much of which has since come to pass. More recently, a BJSM Blog2 invited readers to consider how their future research would look. Given the increased international focus on reducing injury/illness in athletes, it is timely to consider what research needs to be undertaken and acted on to achieve feasible reductions over the next 10 years. ‘Future Studies’3 or ‘Thought Leadership’ happens when a defined group of experts calls attention to what they think will be important for their field in the future. This is common in social science disciplines (eg, finance) and in scientific areas with major implications for policy development (eg, in climate control/environmental science). It has been less commonly applied in medicine, though it has underpinned discussion in areas like cancer research4 and academic medicine.5 Thought leadership involves big picture thinking and can lead to new ideas for major developments over time. There is evidence that such exercises can significantly shape research agenda and priority setting. This novel approach was applied to Sports and Exercise Medicine through asking a select group of international experts to contribute their priority research directions for the next 10 years. This is intended as a starting point only, to stimulate discussion with, and elicit responses from, the broader community interested in the prevention of injury and illness in athletes. International experts were invited to participate if they had delivered ≥1 keynote addresses at the International Olympic Committee (IOC) World Conferences of Prevention of Injury and Illness in Sport in 2011, 2014 or their precursor conferences organised by the Oslo Sports Trauma Research Centre in 2005 and 2008. Of 21 keynote speakers, 12 contributed their views to this paper. The experts covered a range of disciplines, including clinical sports …