Thoracic radiotherapy for limited-stage small cell lung cancer: issues of timing, volumes, dose, and fractionation.

Although meta-analysis of randomized trials comparing chemotherapy alone versus chemotherapy plus thoracic irradiation demonstrated that thoracic radiotherapy reduced mortality by 14%, this analysis probably underestimates the effect of optimally delivered thoracic irradiation integrated with appropriate chemotherapy. However, there remains much debate as to the optimal timing of the radiotherapy and the radiotherapy volume, dose, and fractionation. Theoretically, early use of radiotherapy should reduce the probability of chemotherapy and radiation resistance, accelerated repopulation, and metastatic events. Deferred or sequential radiotherapy potentially allows smaller radiotherapy fields. Of the seven randomized controlled trials examining timing, only those with early chemoradiation have 5-year survival rates in excess of 20%. The "chemoradiation package" can be defined as the time from the start of chemotherapy until the completion of radiotherapy. The best median survival and long-term survival rates have been observed in trials with a chemoradiation package time of less than 6 weeks. Protocols combining chemotherapy and radiotherapy must respect radiobiologic principles concerning the time factor derived from radiotherapy fractionation studies. Copyright 2003, Elsevier Science (USA). All rights reserved.