Tumor Control and Toxicity Following SBRT for Ultracentral, Central and Paramediastinal Lung Tumors

Abstract

Increased rates of toxicity have been described following stereotactic body radiotherapy (SBRT) for centrally located lung tumors within 2 cm of the central airways. Recent studies have defined a new class of “ultracentral” lung tumors directly abutting the proximal airways. We hypothesize that rates of toxicity for ultracentral tumors will exceed that of other central tumors. We report our institutional experience treating ultracentral, central, and paramediastinal lung tumors with SBRT and compare toxicity, disease control, and survival for each cohort. Following institutional review board approval, we retrospectively reviewed the records for all patients with centrally located lung tumors treated with SBRT between September 2009 and July 2017 at our institution. Tumors were classified as central if located within 2 cm of the proximal bronchial tree (PBT), ultracentral if the planning target volume (PTV) touched or overlapped the PBT or esophagus, and paramediastinal if touching the mediastinal pleura but not meeting criteria as central. Actuarial rates of grade 2+ and 3+toxicity, in-field local tumor control (LC), and overall survival (OS) were assessed using the Kaplan-Meier method and compared using a log-rank test. Toxicity was scored using CTCAE V4.03. We identified 68 patients with 69 centrally located lung tumors, including 14 ultracentral, 15 paramediastinal, and 39 central tumors. 53 patients were treated for early stage NSCLC and 15 patients for limited metastases involving the lungs. The median prescription dose was 50 Gy (range: 40-60 Gy) over 5 fractions (range: 3-8) and was similar between cohorts. Median follow up for living patients was 19.7 months (range: 3.3-78.3). Two-year estimates of LC (89%, 85%, and 93%; p=0.72) and OS (76%, 73%, and 72%; p=0.75) for ultracentral, central, and paramediastinal tumors, respectively, were similar between cohorts. Ultracentral tumors were at higher risk of developing grade 2+ toxicity (57.6% vs. 14.2% vs. 7.1%, p= 0.007) at 2 years compared to central and paramediastinal patients. We recorded 2 cases of grade 3 post-obstructive pneumonia in one central and one ultracentral case, and one grade 5 respiratory failure in an ultracentral case. Mean maximum PBT doses were higher for ultracentral cases (55.9 Gy) as compared to central (28.9 Gy) and paramediastinal (12.5 Gy) cases (p <0.001). Oncologic outcomes following SBRT for ultracentral, central, and paramediastinal lung tumors were similar, with LC exceeding 85% at 2 years using a predominantly 5-fraction regimen. Ultracentral lung tumors were associated with increased risk of toxicity in our patient cohort. Additional studies are needed to minimize SBRT toxicity for ultracentral tumors.