Profylactische schedelbestraling bij patiënten met uitgebreid kleincellig longcarcinoom dat reageert op chemotherapie: Minder symptomatische hersenmetastasen en betere overleving

Objective. To determine the effect of prophylactic cranial irradiation (PCI) in patients with extensive-disease small-cell lung cancer (ED-SCLC) who responded to chemotherapy. Design. Randomised, controlled clinical trial; phase III study (EORTC nr 08993-22993; www.clinicaltrials.gov, nr NCT00016211). Method. Patients aged 18-75 years with a functional status according to WHO ≤ 2, and with ED-SCLC and any response to chemotherapy, were randomized to observation (standard care) or PCI. The primary endpoint was time to symptomatic brain metastases. If any pre-defined, key symptom suggesting brain metastases presented, a CT or MRI scan of the brain was performed. The size of the study (143 patients per arm) was determined to detect a hazard ratio (HR) of 0.44 at 80% power with 2-sided α = 0.05. Results. The study accrued 286 patients. PCI decreased the risk of developing symptomatic brain metastases (HR = 0.27 (95% CI: 0.16-0.44; p <0.001)). The cumulative incidence of developing brain metastases within 1 year was 40% in the control group (95% CI: 32-49) and 15% in the PCI group (95% CI: 8-21). PCI prolonged disease-free (HR = 0.76; 95% CI: 0.59-0.96, p = 0.02) and overall survival (HR = 0.68; 95% CI; 0.52-0.88, p = 0.003). The 1-year survival rate was 27% (95% CI: 19-36) for the PCI group versus 13% (95% CI: 8-20) for controls. Acute and late treatment toxicity was acceptable. These side effects did not significantly impact on quality of life. Conclusions. PCI significantly reduced the incidence of symptomatic brain metastases and prolonged both disease-free and overall survival and should be part of standard care in SCLC patients who respond to chemotherapy.