• Branislav Jeremic, Biljana Milicic, Aleksandar Dagovic, Jasna Aleksandrovic, and Slobodan Milisavljevic.
• Department of Oncology, University Hospital, Kragujevac, Yugoslavia. bjeremic@lrz.tu-muenchen.de
• Am. J. Clin. Oncol. 2004 Dec 1; 27 (6): 616-25.

AbstractWe investigated the influence of interfraction interval (IFI) on treatment outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy (Hfx RT) with or without concurrent chemotherapy (CHT). During 3 randomized phase III and 1 phase II study, a total of 536 patients were treated with Hfx RT alone or with concurrent carboplatin/etoposide. Two hundred eighty-five patients were treated with IFI of 4.5-5.0 hours, while 251 patients were treated with IFI of 5.5-6.0 hours. "Shorter" (4.5-5.0 hours) IFI led to better overall survival (OS) (P = 0.0000) and local recurrence-free survival (LRFS) (P = 0.0000). Multivariate analyses showed IFI to be an independent prognosticator of both OS and LRFS. These results were confirmed when we separated all patients (n = 536) into those treated with Hfx RT only (n = 127) and those treated with concurrent RT/CHT (n = 409). Various RT-related high-grade acute toxicity was not different between the 2 IFI, but patients treated with shorter IFI had a significantly higher incidence of hematological toxicity (P = 0.002). None of the late high-grade toxicities were different between the 2 interfraction intervals. Using regression analysis, it was shown that IFI was not a significant predictor of any of acute or late high-grade (> or =3) toxicity. IFI is an important prognosticator of OS and LRFS in patients with stage III NSCLC treated with Hfx RT with or without concurrent carboplatin/etoposide. IFI led to higher incidence only of hematological toxicity, but was not predictive of any acute or late high-grade (> or =3) toxicity. A carefully designed randomized trial seems necessary to give better insight into the issue of optimal IFI in this disease.

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