S340
were higher in patients with vs without events (mean 22Gy vs 11Gy, V5Gy 60% vs 35%, V30Gy 35% vs 14%). On multivariate pair analysis accounting for baseline risk, heart doses remained significant predictors of cardiac events (e.g. Heart mean dose, p¼0.001, HR 1.05 / 1Gy). 2-year competing risk-adjusted rate of symptomatic cardiac events was 11.1% vs 1.5% for Heart mean dose 15Gy vs <15Gy (p¼0.003, HR 6.7). 34 patients (30%) had asymptomatic pericardial effusions. There was no association between heart doses and OS. Conclusion: Clinically significant symptomatic cardiac events following high-dose thoracic RT for Stage III NSCLC occurred in 13% of patients at a median 2 years post-RT, with the rate appearing to be heart dose dependent. RT-associated cardiac toxicity in the definitive treatment of Stage III NSCLC may occur earlier than historically understood, and heart doses should be minimized. Supported in part by NIH grant CA69579. Keywords: radiation heart toxicity, Stage III NSCLC, cardiac, dose escalation
OA24.05 The Nordic HILUS-Trial - First Report of a Phase II Trial of SBRT of Centrally Located Lung Tumors Karin Lindberg,1 Per Bergström,2 Odd Terje Brustugun,3 Silke Engelholm,4 Vitali Grozman,5 Morten Hoyer,6 Kristin Karlsson,5 Azza Khalil,6 Charlotte Kristiansen,7 Ingmar Lax,5 Britta Löden,8 Jan Nyman,9 Gitte Persson,10 Lotte Rogg,11 Peter Wersäll,5 Rolf Lewensohn1 1 Oncology and Pathology, Karolinska Institutet, Stockholm/Sweden, 2Norrlands University Hospital, Umeå/Sweden, 3Department of Oncology, OuhRadiumhospitalet, Oslo/Norway, 4Skånes University Hospital, Lund/Sweden, 5Karolinska University Hospital, Stockholm/Sweden, 6Oncology, Aarhus University Hospital, Aarhus C/Denmark, 7Department of Clinical Oncology, Odense University Hospital, Odense C/Denmark, 8 Centralsjukhuset, Karlstad/Sweden, 9Sahlgrenska University Hospital, Gothenburg/Sweden, 10Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen/Denmark, 11Oslo University Hospital Ullevål, Oslo/Norway Background: Early attempts of stereotactic body radiation therapy (SBRT) of centrally located lung tumors resulted in high toxicity, questioning the utility of the method in this situation. Since then, different risk adapted fractionation schedules with acceptable toxic effects have been reported from various institutions. However, consensus on the tolerability of centrally
Journal of Thoracic Oncology
Vol. 12 No. 1S
located structures to high-fraction doses is still lacking and the clinical toxic effects in relation to dose to organs at risk (OAR) need to be evaluated. Methods: We here report a first toxicity analysis of the HILUS-trial e a prospective Nordic multicenter non-randomized phase II trial of SBRT to centrally located lung tumors. Patients with a centrally located tumor (defined as 1cm from the proximal bronchial tree) from either a primary non-small cell lung cancer (NSCLC) or a progressive metastasis from another solid tumor were eligible for the trial. Maximum tumor diameter was 5 cm. Patients receiving concomitant systemic anticancer therapy or with tumors reaching through the wall of a main bronchus were not eligible. All the patients were treated with 7Gyx8 and stratified to either arm A (¼tumors close to a main bronchus) or arm B (¼tumors close to a lobar bronchus). The aim was to include 30 patients in each arm. Follow-up was conducted every 3rd month during the first 2 years and thereafter every 6th month. The trial was approved by ethical committees in each country. Results: Seventy-four patients (42 in arm A and 31 in arm B) were included between 2011 and 2016. Sixty-five patients experienced side effects from the study treatment; the most common being grade 1-2 dyspnea, grade 1-2 cough and grade 1-2 fatigue. Twenty-one patients (28%) experienced grade 3-5 side effects (atrioventricular block, bleeding, dyspnea, empyema, fatigue, fever, fistula, lung infection, pain, pneumonitis, pneumothorax and ventricular arrhythmia). Seven patients (6 in group A and 1 in group B) may have suffered grade 5 side effects; six patients experienced lethal hemoptysis after a median of 15.5 months (2.5-21months) and one patient suffered from a lethal pneumonitis 5 months post study treatment. Grade 4-5 side effects occurred more frequently in group A than in group B (19% vs 3%). Further analyses of risk factors for serious toxicity in relation to dose-volume parameters and patient- and tumor characteristics will be presented. Conclusion: SBRT of centrally located tumors may be afflicted with high risk of serious toxicity and further evaluation of clinical and dose-volume dependent risk factors are highly warranted. Keywords: side effects, SBRT, stereotactic, central lung tumors
OA24.06 Histologic Subtype of Early-Stage Lung Adenocarcinoma is a Predictor of Failure Patterns after Stereotactic Body Radiation Therapy Jonathan Leeman,1 Andreas Rimner,2 Joseph Montecalvo,2 Meier Hsu,2 Zhigang Zhang,2
January 2017
Donata Von Reibnitz,2 Kelly Panchoo,2 Ellen Yorke,2 Prasad Adusumilli,3 William Travis,4 Abraham Wu5 1 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, Ny/United States of America, 2Memorial Sloan Kettering Cancer Center, New York, NY/NY/United States of America, 3Memorial Sloan Kettering Cancer Center, New York/United States of America, 4Memorial Sloan Kettering Cancer Center, New York, Ny/United States of America, 5Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York/ United States of America Background: Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for earlystage lung cancer. Histologic subtyping in surgically resected lung adenocarcinomas is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. Herein, we describe outcomes following SBRT for early-stage lung adenocarcinoma by histologic subtype. Methods: We identified 119 consecutive patients (124 lesions) with stage I-IIA lung adenocarcinoma who were treated with definitive SBRT at our institution between August 2008 and August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 WHO Classification. Thirty-seven tumors (30%) were of high risk subtype, defined as containing a component of solid and/or micropapillary pattern. Cumulative incidences of local, nodal, regional and distant failure were compared between high risk vs. non-high risk adenocarcinoma subtypes with Gray’s test, and multivariable-adjusted hazard ratios were estimated from propensity score-weighted Cox regression models. Results: Median follow-up for the entire cohort was 17 months and 21 months for surviving patients. The 1-year cumulative incidence of local, nodal, regional and distant failure, respectively, in high risk and non-high risk lesions were 7.3%, 14.8%, 4.0%, 22.7% and 2.7%, 2.6%, 1.2%, 3.6%. Hazard ratios for local, nodal, regional and distant failure, respectively, of high risk lesions compared to non-high risk were 16.8 (95% CI 3.5-81.4), 3.8 (95% CI 0.95-15.0), 20.9 (95% CI 2.3-192.3), 6.9 (95% CI 2.2-21.1). No significant difference was seen with regard to overall survival. Conclusion: Outcomes following SBRT for early-stage adenocarcinoma of the lung are highly correlated with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, histologic subtype based on core biopsies is a novel prognostic factor and may have important implications for patient selection, adjuvant treatment, biopsy methods and clinical trial design.
Abstracts
S341
Keywords: early stage NSCLC, Patterns of failure, SBRT, Adenocarcinoma
OA24.07 The Impact of Population Heterogeneity on the Efficacy of SBRT to the Lung Neil Woody,1 Chandana Reddy,1 Mohamed Abazeed2 Radiation Oncology, Cleveland Clinic, Cleveland/OH/ United States of America, 2Translational Hematology Oncology Research, Cleveland Clinic, Cleveland/OH/United States of America 1
Background: Stereotactic Body Radiation Therapy (SBRT) is the standard of care for medically inoperable patients with early-stage non-small cell lung cancer (NSCLC). However, NSCLC is comprised of several histological subtypes and the impact of this heterogeneity on SBRT treatments has yet to be established. Methods: We analyzed 740 early-stage NSCLC patients treated definitively with SBRT from 2003 through 2015. We calculated cumulative incidence curves using the competing risk method and identified predictors of local failure using Fine and Gray regression. Results: Overall, 72 patients had a local failure with a cumulative incidence of local failure at three years of 11.8%. On univariate analysis, squamous histology, younger age, fewer medical comorbidities, higher BMI, higher PET SUV, central tumors and lower radiation dose were associated with an increased risk of local failure. On multivariable analysis, squamous histology (HR 2.4 p ¼ 0.008) was the strongest predictor of local failure. Patients with squamous cancers fail SBRT at a significantly higher rate than those with adenocarcinomas or NSCLC-not otherwise specified, with three-year cumulative incidences of local failure of 18.9% (95% CI¼ 12.7-25.1%), 8.7% (95% CI¼ 4.6-12.8%), 4.1% (95% CI¼ 0-9.6%), respectively. Conclusion: Our results demonstrate an increased rate of local failure after SBRT in patients with squamous cell carcinoma. Standard approaches for radiotherapy that demonstrate efficacy for a population may not achieve optimal results for individual patients. Establishing the differential dose-responses of SBRT across histological groups is likely to improve efficacy and inform ongoing and future studies that aim to expand indications for SBRT. Keywords: SBRT, Squamous cell carcinoma, precision medicine, local failure