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Time Between the First Day of Chemotherapy and the Last Day of Chest Radiation Is the Most Important Predictor of Survival in Limited-Disease Small-Cell Lung Cancer

From the Departments of Radiotherapy and Pulmonology, University Hospital Maastricht, University Maastricht, Groel en Ontwikkeling; Maastro Clinic, Maastricht, the Netherlands; Department of Human Oncology, University of Wisconsin Medical School, Madison, WI; Respiratory Oncology Unit, Department of Pneumology, University Hospital Leuven; and Leuven Lung Cancer Group, Leuven, Belgium.

Address reprint requests to Dirk De Ruysscher, MD, PhD, University Hospital Maastricht, Department of Radiotherapy, Dr Tanslaan 12, 6229 ET Maastricht, the Netherlands; e-mail: dirk.deruysscher{at}maastro.nl

PURPOSE: To identify time factors for combined chemotherapy and radiotherapy predictive for long-term survival of patients with limited-disease small-cell lung cancer (LD-SCLC).

METHODS: A systematic overview identified suitable phase III trials. Using meta-analysis methodology to compare results within trials, the influence of the timing of chest radiation and the start of any treatment until the end of radiotherapy (SER) on local tumor control, survival, and esophagitis was analyzed. For comparison between studies, the equivalent radiation dose in 2-Gy fractions, corrected for the overall treatment time of chest radiotherapy, was analyzed.

RESULTS: The SER was the most important predictor of outcome. There was a significantly higher 5-year survival rate in the shorter SER arms (relative risk [RR] = 0.62; 95% CI, 0.49 to 0.80; P = .0003), which was more than 20% when the SER was less than 30 days (upper bound of 95% CI, 90 days). A low SER was associated with a higher incidence of severe esophagitis (RR = 0.55; 95% CI, 0.42 to 073; P < .0001). Each week of extension of the SER beyond that of the study arm with the shortest SER resulted in an overall absolute decrease in the 5-year survival rate of 1.83% ± 0.18% (95% CI).

CONCLUSION: A low time between the first day of chemotherapy and the last day of chest radiotherapy is associated with improved survival in LD-SCLC patients. The novel parameter SER, which takes into account accelerated proliferation of tumor clonogens during both radiotherapy and chemotherapy, may facilitate a more rational design of combined-modality treatment in rapidly proliferating tumors.

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

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