Phase I study of accelerated conformal radiotherapy for stage I non-small-cell lung cancer in patients with pulmonary dysfunction: CALGB 39904

Purpose: The optimal treatment for medically inoperable stage I non-small-cell lung cancer (NSCLC) has not been defined. Patients and Methods: Cancer and Leukemia Group B trial 39904 prospectively assessed accelerated, once-daily, three-dimensional radiotherapy for early-stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 or T2N0 NSCLC (< 4 cm) and pulmonary dysfunction. The nominal total radiotherapy dose remained at 70 Gy, while the number of daily fractions in each successive cohort was reduced. Results: Thirty-nine eligible patients were accrued (eight patients each on cohorts 1 to 4 and seven patients on cohort 5) between January 2001 and July 2005. One grade 3 nonhematologic toxicity was observed in both cohort 3 (dyspnea) and cohort 4 (pain). The major response rate was 77%. After a median follow-up time of 53 months, the actuarial median survival time of all eligible patients was 38.5 months. Local relapse was observed in three patients. Conclusion: Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further investigation of this approach is warranted.