The evidence supporting this protocol is provided by a multicentre international individual patient data meta-analysis involving 2103 patients comparing chemotherapy plus thoracic radiation therapy with chemotherapy alone in patients with limited stage small cell lung cancer. Up until 1989, 1111 patients were randomised to receive chemotherapy plus radiation therapy and 992 patients were randomised to receive chemotherapy alone. The primary end point was survival. At three year survival in patients randomised to combined therapy was 14.3 +/- 1.1%, and in patients randomised to chemotherapy alone it was 8.9+/-0.9% (P=0.001).r With modern radiation therapy techniques survival rates have improved; 24% at 5 years with conventional radiation therapy (52.5 Gy in 25 daily fractions over 5 weeks).r
A phase III study by Takada et al. comparing concurrent CRT (using cisplatin and etoposide) to RT alone demonstrated an absolute gain of 5% in overall survival at 5 years (23.7% versus 18.3%) with concomitant chemoradiation therapy.r In this study radiation therapy started on day 2 of the first cycle of chemotherapy and BD fractionation was used.
Despite controversial findings in the literature, most data supports early thoracic radiation therapy beginning with the first or second cycle when cisplatin-based chemotherapy is used. A meta-analysis by Pijls-Johannesma et al. concluded that when platinum-based chemotherapy was used, overall survival rates at both 2 and 5 years were significantly improved when radiation therapy was commenced within 30 days of starting chemotherapy (2 year survival: HR: 0.73, 95% CI 0.57–0.94, p = 0.01; 5-year survival: HR: 0.65, 95% CI 0.45–0.93, p= 0.02).r
The more recent CONVERT trial compared concurrent once daily thoracic radiation therapy (TRT) with 66Gy in 33 fractions to 45Gy in 30 fractions twice daily TRT as per the Turrisi regime, in patients with limited-stage SCLC.r Median overall survival in the twice daily group was 30 months versus 25 months in favour of the twice daily group (HR for death in the once daily group, 1.18, 95% CI: 0.95-1.45, p= 0.14). Toxicity was similar between groups. The trial was designed to show superiority of once daily CRT and was not powered to show equivalence. Arguably therefore if resources permit, twice daily CRT remains superior.
Alternative dose fractionation schedule including in 15 fractions have been commonly used as per Murray et al. and Spiro et al.rr This fractionation schedule allows for the overall treatment time to remain short which has been shown to contribute towards improved outcomes.