POTENTIAL IMPACT ON SURVIVAL OF IMPROVED TUMOR DOWNSTAGING AND RESECTION RATE BY PREOPERATIVE TWICE-DAILY RADIATION AND CONCURRENT CHEMOTHERAPY IN STAGE IIIA NON-SMALL-CELL LUNG-CANCER

Purpose: The main objectives of this study were (a) to ascertain the f easibility and toxicity of preoperative twice-daily radiation therapy and concurrent chemotherapy, surgery, and postoperative therapy in sta ge IIIA (N2) non-small-cell lung cancer (NSCLC), and (b) to evaluate t umor response, resection rate, pathologic tumor downstaging, and survi val. Methods: Eligibility included biopsy-proven N2 lesion (stage IIIA ) by mediastinoscopy, Karnofsky performance score greater than or equa l to 70, and weight loss less than 5% in the 3 months before diagnosis . The treatment program consisted of two courses of preoperative cispl atin, vinblastine, and fluorouracil (5-FU); 42 Gy concurrent radiation at 1.5 Gy per fraction in two fractions per day; surgery on day 57; a nd one more course of postoperative chemotherapy and 12 to 18 Gy of co ncurrent twice-daily radiation. Results: Forty-two patients with stage IIIA (N2) NSCLC (27 men and 15 women, age 38 to 77 years) were enroll ed onto this prospective study. Forty of 42 patients tolerated the int ended dose (42 Gy) of preoperative radiation and 37 of 39 resected pat ients received prescribed postoperative radiation. The intended dose o f chemotherapy was given in 100%, 70%, and 60% of patients for the fir st, second, and third courses of chemotherapy. Marked dysphagia that r equired intravenous hydration was noted in 14% of patients (six of 42) . Myelotoxicities included grade greater than or equal to 3 granulocyt openia in 23% and thrombocytopenia in 6% of 113 chemotherapy courses. Febrile neutropenia that required hospital admission was noted in 9% o f 113 chemotheropy courses. Surgical resection was performed in 93% of patients. Treatment-related mortality was noted in 7% of patients. Th e overall survival rates by the Kaplan-Meier method were 66%, 37%, and 37% at 2, 3, and 5 years, respectively, with a median follow-up time of 48 months. pathologic examination of the surgical specimen showed a downward shift in tumor extent from stage IIIA (N2) to stage II (N1) in 33%, to stage I (N0) in 24% (10 of 42), and to stage 0 (T0N0) in 9. 5%, for a total of 67%. The degree of tumor downstaging was also trans lated into a survival benefit: 5-year survival rates from the time of surgery were 79%, 42%, and 18% for postoperative tumor stages 0 and I, II, and III, respectively (P = .04). Conclusion: Concurrent chemoradi otherapy using twice-daily radiation is an effective induction regimen that resulted in 67% tumor downstaging, and an encouraging 37% 5-year survival rate. The degree of tumor downstaging may be a useful interm ediate end point for survival benefit in stage IIIA (N2) NSCLC. (C) 19 97 by American Society of Clinical Oncology.