Stereotactic body radiation therapy for early-stage lung cancer: are we "all in".

Stereotactic body radiation therapy (SBRT) has rapidly been adopted into clinical practice as an option for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) based on reports of excellent outcomes, often with local tumor control 90%, from centers in North America, Europe, and Asia.1 Although data for metastatic lung tumors are less robust, experience supporting SBRT as a viable alternative to surgical resection in this patient population is growing, and Siva et al.2 provide a comprehensive review of SBRT for pulmonary (oligo) metastases in this issue of the journal. They conclude that SBRT seems both effective and safe in the metastatic setting as a 2-year local tumor control approached 80%, whereas severe toxicity was observed in less than 5% of patients. Although several prospective single-arm SBRT trials have been conducted, the recently reported results of the multicenter prospective Radiation Therapy Oncology Group (RTOG) 0236 trial for early-stage NSCLC are nothing short of remarkable— particularly for a treatment approach just starting to appear on the radar screen at the start of this decade. Fifty-five high-risk patients with T1 or T2 N0 NSCLC were treated with SBRT to a dose of 6000 cGy in three fractions of 2000 cGy (a 10-fold increase in the dose per fraction given with conventionally fractionated radiotherapy).3 With intermediateterm follow-up of 34.4 months (range 4.8–49.4 months), only one relapse in the primary site was observed. Local tumor control in the involved lobe was 90.6% and estimated 3-year survival exceeded 50%. At the same time, treatment seemed tolerable with protocol-specified grade 3 and grade 4 toxic events in 14% and 4% of patients, respectively. It should be kept in mind in assessing these results that all patients had FDG-PET imaging as a part of initial staging evaluation, only lesions located in the lung periphery were treated, and institutions were required to undergo a rigorous quality assurance process to participate.4 The treated population consisted predominantly of women (62%) and T1 lesions (80%). Although many reports suggest SBRT for early-stage NSCLC is associated with limited toxicity, mature prospective results are just starting to appear in the literature. Perhaps the most influential SBRT data come from a prospective phase II study performed at Indiana University.5,6 This trial in essence served as the basis for RTOG 0236, but unlike RTOG 0236 tumor location (e.g., central versus peripheral) was not a condition for eligibility. An increased risk of toxic deaths after SBRT for centrally located lesions was initially reported, although a statistically significant difference in severe toxicity was not seen between central and peripheral lesions with longer follow-up. In addition to tumor location, size of the gross tumor volume was a significant predictor of severe toxicity in the Indiana University trial. In other experiences, pulmonary fatalities after SBRT have been observed secondary to fistula (tracheoesophageal or bronchopulmonary), pneumonitis, and hemoptysis, and tumor location as well as a history of prior radiotherapy and/or