Results from a Prospective Phase 2 Trial Evaluating Safety and Efficacy of Combining Stereotactic Body Radiation Therapy with Radiofrequency Ablation for Centrally Located Lung Tumors

Stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) are both potentially safe and effective alternatives to surgery for primary and metastatic lung tumors. Both strategies are less than optimal however for centrally located tumors with SBRT having higher risks for significant toxicity (damage to serial central structures) and RFA with lower efficacy (heat sink effects). In this study, we evaluated the safety and efficacy of combination SBRT and RFA at lower intensities to see if combined treatments can produce superior outcomes than to each treatment alone. Patients with one or two primary or metastatic lung tumors measuring up to 5 cm in size were enrolled on a prospective phase II trial and treated with SBRT in 3 fractions followed by RFA. The radiotherapy dose was determined based on distance from the proximal bronchial tree, with tumors < 1 cm away receiving a total of 36 Gy and tumors 1-2 cm away receiving 42 Gy. RFA was delivered within 10 days after the last fraction of SBRT. The primary endpoints were local control, toxicity, and degree of decline in lung function. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Sixteen patients with 17 tumors were treated in the study. The median follow-up time was 18 months. Fifteen tumors were evaluable for local control. Local progression was scored for two lesions. The 1-year and 2-year actuarial local control rates were 92% and 80%. Three patients (18.8 %) experienced grade ≥ 3 toxicity (grade 3 chest pain, grade 3 bronchial stenosis, and grade 5 pulmonary hemorrhage). The percent predicted forced expiratory volume in 1 second (FEV1) and functional vital capacity (FVC) decreased by 9% and 8% at 3 months post-treatment, respectively (P = .002 for both). There was not a statistically significant decline in the diffusion capacity of the lungs for carbon monoxide (DLCO) post-treatment. Combining SBRT and RFA for centrally located lung tumors appears to offer reasonable local control and toxicity profile despite the anatomical challenges of this tumor location. RFA may be a reasonable supplement to SBRT when trachea/bronchus, large vessels, or esophageal constraints cannot be met with full dose SBRT, and a biological effective dose of < 100 Gy is delivered due to an ultra-central location or large tumor size.