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Systematic Review Evaluating the Timing of Thoracic Radiation Therapy in Combined Modality Therapy for Limited-Stage Small-Cell Lung Cancer

From the Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, and Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC; and Evanston Northwestern Healthcare, Evanston, IL

Address reprint requests to Daniel B. Fried, MD, PhD, Department of Radiation Oncology, University of North Carolina at Chapel Hill, 101 Manning Dr, Chapel Hill, NC 27514; e-mail: friedd{at}med.unc.edu

PURPOSE: We employed meta-analytic techniques to evaluate early (E) versus late (L) timing of thoracic radiation therapy (RT) in limited-stage small-cell lung cancer (LS-SCLC). In addition, we assessed the impact of radiation fractionation and chemotherapeutic regimen on timing.

METHODS: Randomized trials published after 1985 addressing timing of RT relative to chemotherapy in LS-SCLC were included. Trials were analyzed by risk ratio (RR), risk difference, and number-needed-to-treat methods.

RESULTS: Overall survival (OS) RRs for all studies were 1.17 at 2 years (95% CI, 1.02 to 1.35; P = .03) and 1.13 at 3 years (95% CI, 0.92 to 1.39; P = .2), indicating a significantly increased 2-year survival for ERT versus LRT patients and suggestive of a similar trend at 3 years. Subset analysis of studies using hyperfractionated RT revealed OS RR for ERT versus LRT of 1.44 (95% CI, 1.17 to 1.77; P = .001) and 1.39 (95% CI, 1.02 to 1.90; P = .04) at 2 and 3 years, respectively, indicating a survival benefit of ERT versus LRT. Studies using once-daily fractionation showed no difference in 2- and 3-year OS RRs for ERT compared with LRT. Studies using platinum-based chemotherapy had OS RRs of 1.30 (95% CI, 1.10 to 1.53; P = .002) and 1.35 (95% CI, 1.07 to 1.70; P = .01) at 2 and 3 years, respectively, favoring ERT. Studies using nonplatinum-based chemotherapy regimens had nonsignificant differences in OS.

CONCLUSION: A small but significant improvement in 2-year OS for ERT versus LRT in LS-SCLC was observed, similar to the benefit of adding RT to chemotherapy or prophylactic cranial irradiation. A greater difference was evident for hyperfractionated RT and platinum-based chemotherapy.

Presented previously at the 10th World Conference on Lung Cancer, Vancouver, British Columbia, Canada, August 10–14, 2003; and the 45th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, Salt Lake City, UT, October 19–23, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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