A randomized trial of prophylactic cranial irradiation (PCI) versus no PCI in extensive disease small cell lung cancer after a response to chemotherapy (EORTC 08993–22993)

Abstract

4 Background: Prophylactic cranial irradiation (PCI) significantly reduces the risk of brain metastases (BM) and improves survival in patients with limited disease small cell lung cancer. Development of BM is often accompanied by deterioration of physical and psychological functioning and response to therapy is poor. Patients with extensive disease (ED SCLC) are at high risk for BM. This randomized study assesses PCI in patients with ED SCLC. Methods: Patients (18–75 years; WHO=2) with confirmed ED SCLC and any response to 4–6 cycles of chemotherapy, were randomized to receive PCI (doses ranging from 20 Gy/5 fr to 30 Gy/12 fr) or no PCI. The primary endpoint was the cumulative incidence of symptomatic BM. CT or MRI of the brain was performed whenever any of the pre-defined “key-symptoms” was present at baseline or during follow-up. The study was sized to detect a hazard ratio of 0.44 with 80% power and 2-sided 5% significance (52 events, 287 patients). Results: Between Feb ’01 and Mar ’06, 286 patients entered the trial, 76% with residual disease in the thorax and 71% at distant sites. Baseline characteristics were well balanced. Only 6% of patients in the PCI arm were not treated and 3% interrupted treatment. Acute toxicity was mild: nausea/vomiting was reported by about 30% of PCI-treated cases and about 30% reported late reactions (mostly mild headache). PCI significantly reduced the risk of symptomatic brain metastases (Gray P<0.0001, HR=0.27, CI: 0.16–0.44). The 1-year cumulative incidence of symptomatic BM was 14.6% on PCI (CI 8.3–20.9) versus 40.4% in controls (CI 32.1–48.6). PCI had no impact on extra-cranial progression rates (Gray P>0.1), but it significantly prolonged progression-free survival time (P=0.0218, HR=0.76, CI: 0.59–0.96) and overall survival (P=0.0033, HR=0.68, CI: 0.52–0.88). The 1-year survival rate was 27.1% for the PCI and 13.3% for the control arm. Conclusions: PCI significantly reduces the risk of symptomatic brain metastases, and significantly improves both disease-free and overall survival in patients with ED SCLC. PCI should be offered to all ED patients showing a response to initial chemotherapy. No significant financial relationships to disclose.