Prophylactic cranial irradiation in small cell lung cancer

Some of the characteristics of small cell lung cancer (SCLC) distinguish it from other cell lung cancer types: the risk of early hematogenous dissemination, leading many clinicians to consider it a systemic disease; its marked radiosensitivity and chemosensitivity; and its particular propensity to disseminate in the brain. Even if chemotherapy is the cornerstone treatment, thoracic radiotherapy and prophylactic cranial irradiation (PCI) should be part of the therapeutic strategy, as two individual data-based meta-analyses have shown [1,2]. Throughout the last 20 years, there has been improvement of systemic and local control so that about two thirds of these patients (mainly those with limited disease) who are treated with aggressive induction therapy that combines multidrug chemotherapy and thoracic radiation therapy will be in complete remission. Because of high relapse rates, however, only 15% to 25% of complete responders will be long-term survivors. Because the risk of developing brain metastases increases with the length of survival, brain failures have become a significant cause of relapse, with a cumulative incidence that can be as high as 80% [3,4]. PCI has been introduced as a strategy to prevent dissemination to the uninvolved brain where systemic agents do not cross the blood-brain barrier effectively. In the 1970s, the potential use of central nervous system (CNS) prophylaxis was suggested by Hansen [5], by analogy with pediatric acute lymphoblastic leukemia, for which the use of CNS prophylaxis significantly reduced the incidence of meningeal relapse and improved the cure rate. These observations led to several clinical trials to evaluate the use of PCI in SCLC. By the mid1980s, it was recognized that PCI significantly reduced the incidence of CNS relapses in treated patients compared with patients who did not receive PCI. Despite these positive results, the utility of PCI has been a controversial issue for several years due to the lack of improved survival in individual trials and a possible risk of neurotoxicity and cognitive deficits in long-term survivors, as suggested in retrospective studies [6-9]. Since the publication of a meta-analysis that evaluated the role of PCI in complete responders and showed the benefit of PCI not only in terms of brain control but also in terms of overall survival, PCI is now considered by most clinicians as standard treatment [2,10].