Peer review of structure contouring resulted in significant changes in lung SBRT plans. Recontouring of several plans revealed violations of dose limits, most often involving inadequate PTV coverage. Peer review, especially of target volume delineation, is warranted to improve consistency and quality in lung SBRT planning.

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Introduction Stereotactic ablative radiotherapy (sabr) is a relatively new technique for the curative-intent treatment of patients with inoperable early-stage non-small-cell lung cancer (nsclc). Previous studies have demonstrated a prognostic value for positron emission tomography–computed tomography (pet/ct) parameters, including maximal standardized uptake value (suvmax), metabolic tumour volume (mtv), and total lesion glycolysis (tlg) in lung cancer patients. We aimed to determine which pet/ct parameter is most prognostic of local control (lc) and overall survival (os) in patients treated with sabr for nsclc.Methods We conducted a retrospective review of patients treated with sabr for stage i inoperable nsclc at BC Cancer between 2009 and 2013. The Akaike information criterion was used to compare the prognostic value of the various pet/ct parameters.Results The study included 134 patients with a median age of 76 years. Median tumour diameter was 2.2 cm, gross tumour volume was 8.1 mL, suvmax was 7.9, mtv was 2.4 mL, and tlg was 10.9 suv•mL. The 2-year lc was 92%, and os was 66%. On univariate and multivariate analysis, imaging variables including tumour size, gross tumour volume, suvmax, mtv, and tlg were all associated with worse lc. Tumour size was not associated with significantly worse os, but other imaging variables were. The pet/ct parameter most prognostic of lc was mtv. Compared with suvmax, tlg and mtv were more prognostic of os.Conclusions In patients with early-stage nsclc treated with sabr, mtv appears to be prognostic of lc and os.

BackgroundOligometastases refer to a state of disease where cancer has spread beyond the primary site, but is not yet widely metastatic, often defined as 1–3 or 1–5 metastases in number. Stereotactic ablative radiotherapy (SABR) is an emerging radiotherapy technique to treat oligometastases that require further prospective population-based toxicity estimates.MethodsThis is a non-randomized phase II trial where all participants will receive experimental SABR treatment to all sites of newly diagnosed or progressing oligometastatic disease. We will accrue 200 patients to assess toxicity associated with this experimental treatment. The study was powered to give a 95% confidence on the risk of late grade 4 toxicity, anticipating a < 5% rate of grade 4 toxicity.DiscussionSABR treatment of oligometastases is occurring off-trial at a high rate, without sufficient evidence of its efficacy or toxicity. This trial will provide necessary toxicity data in a population-based cohort, using standardized doses and organ at risk constraints, while we await data on efficacy from randomized phase III trials.Trial RegistrationRegistered through clinicaltrials.gov NCT02933242 on October 14, 2016 prospectively before patient accrual.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4859-7) contains supplementary material, which is available to authorized users.

ImportanceAfter the publication of the landmark SABR-COMET trial, concerns arose regarding high-grade toxic effects of treatment with stereotactic ablative body radiotherapy (SABR) for oligometastases.ObjectiveTo document toxic effects of treatment with SABR in a large cohort from a population-based, provincial cancer program.Design, Setting, and ParticipantsFrom November 2016 to July 2020, 381 patients across all 6 cancer centers in British Columbia were treated in this single-arm, phase 2 trial of treatment with SABR for patients with oligometastatic or oligoprogressive disease. During this period, patients were only eligible to receive treatment with SABR in these settings in trials within British Columbia; therefore, this analysis is population based, with resultant minimal selection bias compared with previously published SABR series.InterventionsStereotactic ablative body radiotherapy to up to 5 metastases.Main Outcomes and MeasuresRate of grade 2, 3, 4, and 5 toxic effects associated with SABR.FindingsAmong 381 participants (122 women [32%]), the mean (SD; range) age was 68 (11.1; 30-97) years, and the median (range) follow-up was 25 (1-54) months. The most common histological findings were prostate cancer (123 [32%]), colorectal cancer (63 [17%]), breast cancer (42 [11%]), and lung cancer (33 [9%]). The number of SABR-treated sites were 1 (263 [69%]), 2 (82 [22%]), and 3 or more (36 [10%]). The most common sites of SABR were lung (188 [34%]), nonspine bone (136 [25%]), spine (85 [16%]), lymph nodes (78 [14%]), liver (29 [5%]), and adrenal (15 [3%]). Rates of grade 2, 3, 4, and 5 toxic effects associated with SABR (based on the highest-grade toxic effect per patient) were 14.2%; (95% CI, 10.7%-17.7%), 4.2% (95% CI, 2.2%-6.2%), 0%, and 0.3% (95% CI, 0%-0.8%), respectively. The cumulative incidence of grade 2 or higher toxic effects associated with SABR at year 2 by Kaplan-Meier analysis was 8%, and for grade 3 or higher, 4%.Conclusions and RelevanceThis single-arm, phase 2 clinical trial found that the incidence of grade 3 or higher SABR toxic effects in this population-based study was less than 5%. Furthermore, the rates of grade 2 or higher toxic effects (18.6%) were lower than previously published for SABR-COMET (29%). These results suggest that SABR treatment for oligometastases has acceptable rates of toxic effects and potentially support further enrollment in randomized phase 3 clinical trials.Trial RegistrationClinicalTrials.gov Identifier: NCT02933242

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Jaswal JS, Lund CR, Keung W, Beker DL, Rebeyka IM, Lopaschuk GD. Isoproterenol stimulates 5=-AMP-activated protein kinase and fatty acid oxidation in neonatal hearts. Am J Physiol Heart Circ Physiol 299: H1135-H1145, 2010. First published July 23, 2010 doi:10.1152/ajpheart.00186.2010.-Isoproterenol increases phosphorylation of LKB, 5=-AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC), enzymes involved in regulating fatty acid oxidation. However, inotropic stimulation selectively increases glucose oxidation in adult hearts. In the neonatal heart, fatty acid oxidation becomes a major energy source, while glucose oxidation remains low. This study tested the hypothesis that increased energy demand imposed by isoproterenol originates from fatty acid oxidation, secondary to increased LKB, AMPK, and ACC phosphorylation. Isolated working hearts from 7-day-old rabbits were perfused with Krebs solution (0.4 mM palmitate, 11 mM glucose, 0.5 mM lactate, and 100 mU/l insulin) with or without isoproterenol (300 nM). Isoproterenol increased myocardial O 2 consumption (in J·g dry wt Ϫ1 ·min Ϫ1 ; 11.0 Ϯ 1.4, n ϭ 8 vs. 7.5 Ϯ 0.8, n ϭ 6, P Ͻ 0.05), and the phosphorylation of LKB (in arbitrary density units; 0.87 Ϯ 0.09, n ϭ 6 vs. 0.59 Ϯ 0.08, n ϭ 6, P Ͻ 0.05), AMPK (0.82 Ϯ 0.08, n ϭ 6 vs. 0.51 Ϯ 0.06, n ϭ 6, P Ͻ 0.05), and ACC-␤ (1.47 Ϯ 0.14, n ϭ 6 vs. 0.97 Ϯ 0.07, n ϭ 6, P Ͻ 0.05), with a concomitant decrease in malonyl-CoA levels (in nmol/g dry wt; 0.9 Ϯ 0.9, n ϭ 8 vs. 7.5 Ϯ 1.3, n ϭ 8, P Ͻ 0.05) and increase in palmitate oxidation (in nmol·g dry wt Ϫ1 ·min Ϫ1 ; 272 Ϯ 45, n ϭ 8 vs. 114 Ϯ 9, n ϭ 6, P Ͻ 0.05). Glucose and lactate oxidation were increased (in nmol·g dry wt Ϫ1 ·min Ϫ1; 253 Ϯ 75, n ϭ 8 vs. 63 Ϯ 15, n ϭ 9, P Ͻ 0.05 and 246 Ϯ 43, n ϭ 8 vs. 82 Ϯ 11, n ϭ 6, P Ͻ 0.05, respectively), independent of alterations in pyruvate dehydrogenase phosphorylation, but occurred secondary to a decrease in acetyl-CoA content and acetyl-CoA-to-free CoA ratio. As acetyl-CoA levels decrease in response to isoproterenol, despite an acceleration of the rates of palmitate and carbohydrate oxidation, these data suggest net rates of acetyl-CoA utilization exceed the net rates of acetyl-CoA generation.inotropes; neonatal heart; adenosine 5=-monophosphate-activated protein kinase; malonyl-coenzyme A; palmitate oxidation; carbohydrate oxidation THE NEWBORN (1-DAY OLD) RABBIT heart derives 44 -60% of its ATP requirements from glycolysis, while lactate oxidation meets the remainder of ATP demand (35). There is a maturational increase in the contribution of fatty acid ␤-oxidation to cardiac ATP generation (26). The maturational increase in fatty acid ␤-oxidation is accompanied by the increased expression and activity of cardiac 5=-AMP-activated protein kinase (AMPK) (39) and a decrease in the activity of acetyl-CoA carboxylase (ACC) (37), the enzyme that synthesizes malonylCoA. During this time period (between 1 and 7 days), there is also an increase in the activity of malonyl-CoA decarboxylase (MCD), the enzyme that degrades malo...