Randomized phase III trial of prophylactic cranial irradiation versus observation in patients with fully resected stage IIIA-N2 non-small-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy
Mené sur 156 patients atteints d'un cancer du poumon non à petites cellules de stade IIIA-N2 traité par résection et présentant un risque élevé de métastases cérébrales après une chimiothérapie adjuvante, cet essai de phase III évalue, du point de vue de la survie sans maladie et de la survie globale, l'intérêt d'une radiothérapie prophylactique du cerveau
Background : This study compared prophylactic cranial irradiation (PCI) with observation in patients with resected stage IIIA-N2 non–small-cell lung cancer (NSCLC) and high risk of cerebral metastases after adjuvant chemotherapy. Patients and methods : In this open-label, randomized, phase III trial, patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high cerebral metastases risk without recurrence after postoperative adjuvant chemotherapy were randomly assigned to receive PCI (30 Gy in 10 fractions) or observation. The primary end point was disease-free survival (DFS). The secondary end points included the incidence of brain metastases, overall survival (OS), toxicity and quality-of-life. Results : This trial was terminated early after the random assignment of 156 patients (81 to PCI group and 75 to control group). The PCI group had significantly lengthened DFS compared with the control group, with a median DFS of 28.5 months versus 21.2 months (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.46-0.98; P=0.037). PCI was associated with a decrease in risk of brain metastases (The actuarial 5-year brain metastases rate, 20.3% vs 49.9%; HR, 0.28; 95% CI, 0.14 to 0.57; P<0.001). The median OS was 31.2 months in the PCI group and 27.4 months in the control group (HR, 0.81; 95% CI, 0.56-1.16; P=0.310). While main toxicities were headache, nausea/vomiting and fatigue in the PCI group, they were generally mild. Conclusion : In patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.