Decreased metastasis and improved survival with early thoracic radiotherapy and prophylactic cranial irradiation in combined-modality treatment of limited-stage small cell lung cancer

Abstract

In an attempt to verify the relative efficacy of early concurrent vs. sequential timing of thoracic radiotherapy (TRT) and platinum/etoposide chemotherapy, 48 patients with limited-stage small cell lung cancer treated with either early-concurrent (29 patients) or sequential (19 patients) TRT and platinum/etoposide chemotherapy were evaluated. Disease-specific prognostic variables and the role of prophylactic cranial irradiation (PCI) were also analyzed. Thirty-four patients (71%) received TRT to a dose of 45 Gy in 25 fractions (range, 30-55 Gy). Most patients (75%) received 4-6 cycles of chemotherapy. Twenty-one of 27 patients achieving a complete response after completion of TRT and chemotherapy received PCI. Median follow-up was 29.3 months (range, 12-98 months). Variables of potential prognostic significance were evaluated by both univariate and multivariate analysis. The absolute and relapse-free survival rates for all patients were 42% and 35% at 2 years and 32% and 31% at 5 years, respectively. Thirty-six sites of failure were observed in 27 patients. Thoracic recurrence occurred in nine patients, and the central nervous system (CNS) was the most common site of distant failure (15 patients). Multivariate analysis demonstrated that (a) early concurrent TRT and chemotherapy vs. chemotherapy followed by sequential TRT and (b) disease volume [less than or greater than one-third of the thoracic width] were significantly predictive for survival (P=0.036 and P=0.05, respectively). Rates of control of thoracic disease were 79% for patients with a disease volume less than one-third of the thoracic width vs. 36% for disease volumes greater than one-third of the thoracic width (P=0.0009). Early concurrent TRT and chemotherapy resulted in a significantly lower incidence of distant metastasis (26% for concurrent vs. 63% for sequential; P=0.008). In patients who received PCI, the CNS control rate was 86% vs. 56% in patients not treated with PCI. Our findings suggest that (a) treatment with early concurrent TRT and platinum/etoposide chemotherapy may improve survival when compared with sequential treatment and (b) PCI for patients with complete systemic responses is effective in preventing CNS recurrence. We also conclude that thoracic disease volume is a significant prognostic factor for both local control and overall survival.