Final report of the 70.2-Gy and 75.6-Gy dose levels of a phase I dose escalation study using three-dimensional conformal radiotherapy in the treatment of inoperable non-small cell lung cancer

PURPOSE AND OBJECTIVE Three-dimensional conformal radiotherapy (3D-CRT) is a mode of high-precisi on radiotherapy designed to increase the tumor dose and decrease the dose t o normal tissues. This study reports the final results of the first two dos e levels (70.2 Gy and 75.6 Gy) of a phase I dose-escalation study using 3D- CRT for the treatment of non-small cell lung cancer. PATIENTS AND METHODS Fifty-two patients were treated with 3D-CRT without chemotherapy. The media n age was 67 years (range, 39-82 years). The majority of patients had local ly advanced cancer. Tumor was staged as I/II in 10%, IIIA in 40%, and IIIB in 50%. Radiation was delivered in daily fractions of 1.8 Gy, 5 days a week A radiation dose level was considered complete when 10 patients received t he intended dose nithout unacceptable acute morbidity. Toxicity was scored according to the Radiation Therapy Oncology Group grading scheme. RESULTS Twenty patients were initially assigned to the 70.2-Gy la-el; 14 of them re ceived the intended dose. Three patients experienced severe acute toxicity, two with grade 3 (requiring steroids or oxygen) and a third with grade 5 ( Eatal) acute radiation pneumonitis. Because of the grade 5 pulmonary toxici ty, the protocol was modified, and only patients with a calculated risk of normal tissue complication of less than 25% were eligible For dose escalati on. Patients who had a normal tissue complication probability (NTCP) of gre ater than 259/0 received a lower dose of radiation. An additional 18 patien ts were entered on the modified study; 11 of them received 70.2 Gy. One pat ient experienced grade 3 acute pneumonitis. Despite dose reduction in four patients because of an unacceptably high NTCP, two additional patients deve loped grade 3 pulmonary toxicity. Fourteen patients were accrued to the 75. 6-Gy dose level, and 10 received the intended dose. One of the 10 patients experienced grade 3 pulmonary toxicity and one developed grade 3 esophageal toxicity. Three patients were treated to lower doses as a result of their calculated NTCP without toxicity; and one patient refused treatment The 2-y ear local control, disease-free survival, and overall survival rates were 3 7%, 12%, and 24%, respectively The median survival time was 11 months. DISCUSSION Treatment to 70.2 Gg and 75.6 Gy using SD-CRT,vas delivered with acceptable morbidity when NTCP constraints were observed. Local control was encouragi ng in these patients with locally advanced disease. Patients are currently being accrued to the 81-Gp level of the study.