Abstract Background Stereotactic ablative radiotherapy (SABR) is effective for thoracic cancer and metastases; however, adverse effects are greater for central tumors. We evaluated factors affecting outcomes and toxicities after SABR for patients with primary lung and oligometastatic tumors. Patients and methods We retrospectively identified consecutive patients with centrally located lung tumors that were treated at our hospital from 2009-2016. The effects of patient, disease, and treatment-related parameters on local control (LC), overall survival (OS), and toxicity-free survival (TFS) were evaluated with multivariate analyses. Results Among 65 consecutive patients identified with 70 centrally located tumors, 20 tumors (28%) were reirradiated. Median (range) total dose for all tumors was 55 (30–60) Gy in 5 (3–10) fractions. Radiographic complete response was obtained in 43 lesions (61%). None of the analyzed factors were correlated with complete response. After a median follow-up of 57 (95% CI, 48–65) months, 10 tumors (14%) relapsed and 37 patients (57%) died; the actuarial 2- and 5-year OS rates were 52% and 28%, respectively. Median OS was significantly lower in patients with grade 3 or higher toxicity vs . lower toxicity (5 vs . 39 months; P < 0.001). Among 17 severe toxicities, 5 were grade 5, and 3 of them were reirradiated to the same field. Grade 3 to 5 TFS was lower with vs . without reirradiation (2-year TFS, 63% vs . 96%; P = 0.02). Conclusions Our study showed that modern SABR is effective for central lung tumors, and toxicities are acceptable. SABR for reirradiated central lung lesions and possibly for lesions abutting the tracheobronchial tree may result in higher risk of serious toxicities.
Objective Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome‐wide association analysis of Takayasu arteritis. Methods Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1‐Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. Results We identified genetic susceptibility loci for Takayasu arteritis with a genome‐wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10 −9 ), RPS9 / LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10 −8 ), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10 −10 ). The genetic susceptibility locus in RPS9 / LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin‐like receptor gene LILRB3 ( P = 2.29 × 10 −8 ). In addition, we identified candidate susceptibility genes with suggestive levels of association ( P < 1 × 10 −5 ) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1 , and PTK2B . Conclusion Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.