Results of a phase I dose-escalation study using single-fraction stereotactic radiotherapy for lung tumors

Background: The purpose of this study was to report initial results of a phase I study using single-fraction stereotactic radiotherapy (RT) in patients with inoperable lung tumors. Methods: Eligible patients included those with inoperable T1-2N0 non-small cell lung cancer (NSCLC) or solitary lung metastases. Treatments were delivered by means of the CyberKnife. All patients underwent computed tomography-guided metallic fiducial placement in the tumor for image-guided targeting. Nine to 20 patients were treated per dose cohort starting at 15 Gy/fraction followed by dose escalation of 5 to 10 Gy to a maximal dose of 30 Gy/fraction. A minimal 3-month period was required between each dose level to monitor toxicity. Results: Thirty-two patients (21 NSCLC and 11 metastatic tumors) were enrolled. At 25 Gy, pulmonary toxicity was noted in patients with prior pulmonary RT and treatment volumes greater than 50 cc; therefore, dose escalation to 30 Gy was applied only to unirradiated patients and treatment volume less than 50 cc. Ten patients received doses less than 20 Gy, 20 received 25 Gy, and two received 30 Gy. RT-related complications were noted for doses greater than 25 Gy and included four cases of grade 2 to 3 pneumonitis, one pleural effusion, and three possible treatment-related deaths. The 1-year freedom from local progression was 91% for dose greater than 20 Gy and 54% for dose less than 20 Gy in NSCLC (p = 0.03). NSCLC patients had significantly better freedom from relapse (p = 0.003) and borderline higher survival than those with metastatic tumors (p = 0.07). Conclusions: Single-fraction stereotactic RT is feasible for selected patients with lung tumors. For those with prior thoracic RT, 25 Gy may be too toxic. Higher dose was associated with improved local control. Longer follow-up is necessary to determine the treatment efficacy and toxicity.