Small cell lung cancer (SCLC) has several features that distinguish it from other tumor types of lung cancer: the risk of early hematogenous dissemination, its marked radiosensibility and chemosensibility but also its particular propensity to disseminate in the brain. Even if chemotherapy is the cornerstone treatment in both limited and extensive disease, thoracic radiotherapy and prophylactic cranial irradiation (PCI) should be part of the therapeutic strategy in a subset of patients with limited disease (LD) as shown in two metaanalyses.¹,² PCI should be considered among patients with extensive disease who respond to treatment.²,³ In the past years, there has been improvement of both systemic and local control so that about two thirds of these patients, mainly those with LD, treated with aggressive induction therapy combining multidrug chemotherapy and thoracic radiation therapy will be put in complete remission. However, there is a high risk of relapse, so that only 15% to 25% of complete responders will be long-term survivors. Brain failures, for instance, have become a significant cause of relapse as the risk of developing brain metastases increases with length of survival to a cumulative risk that can be as high as 80%.⁴,⁵ PCI has been developed as a strategy to prevent dissemination to the uninvolved brain, where systemic agents do not cross the blood-brain barrier effectively.⁶ Thus, several studies have been undertaken that proved PCI would significantly reduce the incidence of a central nervous system (CNS) relapse compared with patients who did not receive PCI. However, in spite of the positive results of several retrospective and prospective studies, the utility of PCI has been a controversial issue for several years because of the lack of improvement in survival in individual trials and a possible risk of neurotoxicity and cognitive deficits in long-term survivors.⁷,⁸,⁹,¹⁰ Since the publication of a metaanalysis on PCI in SCLC complete responders, showing the benefit of PCI not only in terms of brain control but also in terms of survival, PCI is now considered by most clinicians as standard treatment.²

Because brain metastases are frequent and difficult to treat, accompanied by distressing and sometimes life-threatening symptoms, prophylactic treatment seems a good alternative. At the time of initial diagnosis, up to 24% of patients may have brain metastases if magnetic resonance imaging (MRI) is used as initial workup.⁵,⁶,¹¹ Brain metastases may occur in 50% to 80% of 2-year survivors; in patients who achieve a complete response, the incidence of cerebral metastasis as sole site of initial relapse varies between 14% and 45% at 2 years.¹²,¹³,¹⁴ Historically, chemotherapeutic agents have had a limited role in the treatment of cerebral metastases because of the inability of cytostatic drugs to cross the blood-brain barrier, situated in the endothelium of cerebral microvessels. However, more recent studies have reported efficacy of chemotherapy alone, with response rates on brain metastases ranging from 40% to 76%.¹⁵,¹⁶,¹⁷,¹⁸ Chemotherapy-administered postradiation could also be more effective by abrogation of the blood-brain barrier¹⁹; however, that may also increase toxicity as well. Radiation therapy has remained the most widely accepted treatment modality for brain metastases with improvement of neurological symptoms in 56% to 92% of patients.⁵,²⁰,²¹,²²,²³ However, even if the symptomatic relief is of some benefit, quality of life (QOL) after overt brain metastasis is poor, and overall survival after development of brain metastases is low with median survival times ranging from 1.5 to 4.5 months.²¹,²³,²⁴,²⁵,²⁶,²⁷