Patterns of failure after prophylactic cranial irradiation in small-cell lung cancer:: analysis of 505 randomized patients

Background: Prophylactic cranial irradiation (PCI) has a beneficial effect on overall survival in patients with small-cell lung cancer (SCLC) in complete remission as shown in a worldwide meta-analysis. The current analysis aimed to evaluate PCI effects on patterns of failure in this patient category. Patients and methods: The Institut Gustave-Roussy coordinated two parallel randomized studies including a total of 511 patients with SCLC. Patients were randomly assigned to either PCI (24 Gy in eight fractions and 12 days) or no PCI. Patterns of failure were analyzed according to (i) total event rates and (ii) isolated First site of relapse using a competing risk approach. Results: Five hundred and five patients were analyzed. The 5-year cumulative rate of brain metastasis as an isolated first site of relapse was 37% in the control group and 20% in the PCI group (P <0.001). The overall 5-year rates of brain metastasis were 59% and 43%, respectively [relative risk (RR) 0.50 P <0.001]. The 5-year overall survival rates, were 15% in the control group and 18% in the PCI group (RR 0.84; P = 0.06). Conclusions: PCI decreased significantly the risk of brain metastasis. Other events were not influenced. The relative death risk reduction was of borderline significance. Results reported as isolated first cause of failure and subsequent competing events may explain why a major treatment effect on brain metastases rate has a rather moderate effect on survival.