Combined modality treatment for resected advanced non-small cell lung cancer: local control and local recurrence

The purpose of this study was to compare the effect of post-operative thoracic radiation with or without systemic chemotherapy on survival and recurrence patterns in patients subjected to thoracotomy with curative intent, but subsequently found to have residual tumor in the resected margin or metastasis in the highest paratracheal lymph node. All patients were treated with postoperative mediastinal irradiation and randomized to receive or not receive combination chemotherapy (cytoxan, adriamycin, and platinum) for 6 months beginning concurrently with radiation. Of the 172 patients randomized, 164 were eligible for analysis. The mean time since randomization for the eligible patients is 4.2 years. Radiation therapy was administered to all patients by split course regimen [20 Gy in 5 fractions over 5 days]. Two such courses were given with a 3-week interval. The initial recurrence rates for both in-field recurrence and distant relapse were reduced in the combined postoperative radiation therapy and chemotherapy group, although only the latter difference achieved statistical significance (p = 0.01). Also, local recurrence overall (not restricted to initial recurrences) is examined as a function of histology, extent of residual disease after resection, and T and N status. The treatment effect achieves statistical significance only for patients with macroscopic residual (p = .023) or T3 tumor (p = .010). The combined therapy group of patients have a significantly longer recurrence-free survival [p = 0.006 by the two-sided Mantel-Haenszel logrank test] which fails, however, to translate to a significant difference in overall survival (p = 0.146). Median survival of the entire group is 14.5 months with 34% alive 2 years after resection. Most of the initial recurrences (82%) have been systemic, with brain being the most common site. Distant failure, therefore, remains an important problem even in the favorable prognosis subset of patients with advanced NSCLC, but combined modality approaches can produce improved recurrence-free survival.