Early Outcomes from a Prospective Phase II Trial Evaluating Safety and Efficacy of Combining SBRT with RFA for Centrally Located Lung Tumors

Lung tumors near central airways are difficult to treat with SBRT or radiofrequency ablation (RFA) due to safety and technical considerations. Lower control rates or unacceptable toxicity to central organs have been seen when treating central compared to peripheral tumors. We hypothesized a combined approach (SBRT/RFA), at lower intensity for each, can have synergistic effects to improve local control (LC) while reducing treatment-related morbidity. An IRB-approved, single-arm Phase II study was designed for medically inoperable patients with primary or recurrent central lung tumors. Tumors 1 - 2 cm from the tracheal-bronchial tree (TBT) received 14 Gy x 3, and those within 1 cm of TBT received 12 Gy x 3 followed by RFA (within 10 days). Patients with tumors that were > 5 cm and those with prior thoracic RT near the target were ineligible. Primary endpoints were to achieve no more than 20% grade 3 thoracic, esophageal, or cardiac toxicity and at least 80% one-year LC rate using a Bayesian sequential monitoring design. Data monitoring was performed by the institutional Data Safety Monitoring Board. Serum was collected for biomarker studies pre, during, and post-treatment. PFTs were obtained pre, and at 3 and 12 months post-treatment to assess impact on lung function. Follow-up included clinical exams, PET-CTs at 6 weeks and one year, as well as CTs at 3, 6, and 9 months post-treatment. A local failure (LF) was defined on follow-up CT by RECIST (v1.0) or serial increase in FDG at 6 weeks and 1 year. Toxicity was defined by CTACE (v3.0). From 2010 - 2013, 13 patients were enrolled, with 12 patients (13 lesions) eligible for analysis (one withdrew consent). Four patients had primary NSCLC with the remaining patients having metastatic lesions. Median follow-up time was 20.1 months (range: 2.7-42.9), and median overall survival was 32 months by Kaplan-Meier method. There was one LF at 20 months with 2 and 3-year LC rates of 85.7%. Increase tumor volume (median 22 cc) did not predict for LF. There were no grade 3 - 5 cardiac or esophageal toxicities. There was one grade 3 chest-wall toxicity, and one fatal hemoptysis (thoracic toxicity) possibly related to injury to the TBT at 7 months (14 Gy x 3, max bronchus dose = 34.3 Gy, V30Gy = 0.11 cc, V20Gy = 0.22 cc). This patient met the protocol specified dose limits for trachea/ipsilateral bronchus (Max 37.5 Gy, V21 Gy < 1 cc). Cumulative rates of grade 3 - 5 thoracic toxicities were 8.3%. Neither increase TBT dose nor lung V20Gy correlated with higher rates of thoracic toxicity (p > 0.05). SBRT/RFA treatment appears effective for centrally located lung tumors. Early results suggest an acceptable safety profile. However, due to potential untoward and poorly understood interactions between the two modalities, further investigation is required. Caution is advised when SBRT/RFA is offered outside of a clinical trial.