Cranial irradiation for preventing brain metastases of small cell lung cancer in patients in complete remission

Abstract

Background: Prophylactic cranial irradiation halves the rate of brain metastases in patients with small cell lung cancer. Individual randomized trials conducted on patients in complete remission were unable to clarify whether this treatment improves survival. Objectives: This study aims to test whether prophylactic cranial irradiation prolongs survival of patients with small cell lung cancer in complete remission. Search methods: Published and unpublished trials were eligible. Electronic databases (Medline, Cancerlit, Excerpta Medica, Biosis from 1965 to 1998), reference lists of trial publications, review articles and relevant books were used to identify potentially eligible trials. The search was also guided by discussions with investigators and experts, and the examination of meeting proceedings and of the Physician Data Query clinical trial registry. Selection criteria: Randomized trials comparing prophylactic cranial irradiation with no prophylactic cranial irradiation in patients with small cell lung cancer in complete remission. Data collection and analysis: Meta-analysis based on updated individual data. The main endpoint was survival. Main results: Seven trials with a total of 987 participants were included. The relative risk of death in the treatment group compared to the control group was 0.84 (95% confidence interval=0.73 to 0.97, P=0.01), corresponding to a 5.4 percent increase in the 3-year survival rate (from 15.3 percent in the control group to 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased disease-free survival (relative risk=0.75, 95% confidence interval=0.65 to 0.86, P<0.001) and decreased the risk of brain metastases (relative risk=0.46, 95% confidence interval=0.38 to 0.57, P<0.001). Increasing doses of irradiation decreased the risk of brain metastases when four groups (8 Gy, 24-25 Gy, 30 Gy, 36-40 Gy) were analyzed [trend test, P=0.02], but the effect on survival did not differ significantly according to the dose. We found a trend (P=0.01) for a decrease in the brain metastasis risk in favour of earlier administration of cranial irradiation after the initiation of induction treatment. Authors' conclusions: Prophylactic cranial irradiation significantly improves survival and disease-free survival for patients with small cell lung cancer in complete remission. Further clinical trials are needed to confirm the potential greater benefit on brain metastasis rate suggested when cranial irradiation is given earlier or at higher doses.