Escalating SBRT Dose to Hypoxic Centers of Large Pulmonary Tumors via Simultaneous Integrated Boost Confers Effective Local Control with Minimal Toxicity

Abstract

Hypoxia confers radio-resistance to tumor cells and drives malignant disease progression. SBRT treatment of large (>5.0 cm) pulmonary tumors pose significant dosimetric challenges in minimizing dose to adjacent organs at risk (OARs). Here, we detail the use of SBRT with simultaneous integrated boost (SIB) to the hypoxic centers of large pulmonary masses with effective local control and minimal normal tissue toxicity. Highly conformal treatment plans utilized 3-4 non-coplanar VMAT arcs with 6MV-FFF (1400 MU/min) and 4D-CT on TrueBeam to deliver 50 Gy in 5 fractions to the planning target volume (PTV). SIB dose of 60 Gy was delivered to a 1-cm internal margin from the gross tumor volume (GTV). Dose was calculated using Acuros-based engine. Pre-treatment Conebeam CT imaging was used for patient setup and verification. Treatments were delivered in < 15 minutes. Patients underwent post-treatment clinical evaluation and CT imaging in 3-month intervals to assess changes in tumor size and post-radiation sequelae. Clinical outcomes reported include treatment response and toxicity. Twenty-six patients with large, centrally (n = 13) or peripherally (n = 13) located tumors were evaluated; this included 16 NSCLC patients with T2-T3N0 disease and 5 with pulmonary metastases from distant sites. One patient had declined surgery, while 25/26 (96.1%) were deemed medically inoperable. All plans met RTOG-0813 requirements for target coverage and dose to OARs. Median follow-up interval was 11 months (0 to 23 months). Twenty-one of 26 (80.7%) patients received post-treatment CT imaging within 6 months of SBRT. Local control was achieved in 20/21 (95.2%) patients; one patient with a peripherally located tumor progressed outside the treatment field. Acute toxicity profile amongst the 25 patients assessed included grade 1 fatigue (n = 2), grade 1 rib pain (n = 1), and grade 2 pulmonary fibrosis (n = 1). Otherwise, 22/25 (88%) patients reported no radiation induced toxicities. Subgroup analysis was performed on patients with centrally located tumors, defined as located <2 cm from the hilum, heart, or bronchial trees. One of 13 (7.6%) patients with central tumors reported grade 1 rib pain; otherwise, no radiation induced adverse effects were observed. All patients with centrally located lung tumors experienced local control on surveillance imaging. SBRT with SIB to the hypoxic centers of large pulmonary masses is a safe, efficacious treatment that confers improved local control while maintaining dose to adjacent OARs. This study demonstrates the feasibility of delivering doses up to 60 Gy to the hypoxic centers of large lung tumors, while decreasing local tumor burden, minimizing treatment mobility, and improving clinic workflow. SBRT with SIB shortens treatment course to 5 fractions (in contrast to the traditional daily 30 fractions), thus improving patient comfort and compliance.