The role of prophylactic brain irradiation in small cell lung cancer treatment

To review the effectiveness and safety of prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC).

Brain metastases are frequent in SCLC with a cumulative incidence of 25% among 1,202 in 17 trials, and a 3-5 months median survival from first occurrence. The 5-year cumulative rate of brain metastases as isolated first site of relapse was 37% among 260 patients without PCI compared to 20% among 245 with PCI in two randomised trials (p < 0.001). A meta-analysis on seven randomised trials of PCI versus no PCI including 987 patients in complete remission without brain metastases or prior brain irradiation showed statistically significant effect in favour of PCI on survival, disease free survival, and risk of brain metastases (relative risks being 0.84, 0.75, and 0.46, and p-values being 0.01, < 0.001, and < 0.001, respectively). Two randomised trials evaluated neurotoxicity in totally 350 patients before PCI and found abnormalities in 24-60%. Repeated examination during the following years revealed no differences on cerebral CT-scans or neuropsychological testing between PCI patients or controls. A review including 42 PCI trials with 4,749 patients revealed the optimal total radiotherapy dose to be 30-35 Gy given as 2 Gy fractions. Also 24 Gy in 3 Gy fractions appear safe based on data from a large randomised study. Both the former study and the meta-analysis suggested early PCI to be better than late.

PCI improves both overall and disease free survival and decreases the risk for brain relapse in SCLC patients in complete remission. PCI should be applied early, and useful and safe doses may be 30-36 GY in 2-3 Gy fractions, though future studies may further illuminate the optimal dose, fractionation and timing.