58 Lekic M et al. / Small-cell lung cancer and brain metastases that could lower the rates of brain relapse and pos- sibly increase patients’ survival because it is well known that the central nervous system is relatively refractory to chemotherapy due to the blood-brain barrier. PCI was found to improve survival rates significantly not only in limited stage but also in ex- tensive stage SCLC responding to chemotherapy, and is now recommended as a part of the standard treatment patients with LD and ED SCLC.19,21-27 The first meta-analysis by Auperin et al. in 1999 report- ed the 5.4% increase in the rate of survival at three years for patients achieving complete response on primary chemoradiation therapy.24 It was fol- lowed by a large EORTC (European Organisation for Research and Treatment of Cancer) trial that confirmed significant benefit of PCI in all patients achieving response (complete or partial) to first- line systemic therapy.25 Based on these observa- tions PCI represents a standard treatment approach nowadays, which ultimately results in a lower rate of brain metastases diagnosed during the course of the disease.19 However, the percentage of patients presenting with brain metastases at the time of di- agnosis remains stable, i.e. between 14-20%. Our group of patients with PCI, was (similar as group with brain metastases alone) too small to allow a separate analysis. The question remains on optimal treatment of brain metastases in SCLC. For extensive central nerve system involvement the treatment of choice is WBRT, however the optimal treatment strategy for a solitary brain metastasis, which is quite rare in SCLC, has still not been defined. It is known for some other cancers, such as non-small cell lung cancer and breast cancer, that surgical or stereotac- tic irradiation of solitary brain metastasis followed by WBRT gains better survival rates compared to WBRT alone.9,10 Despite the lack of scientific evi- dence based on randomized trials such an approach may be superior in selected SCLC patients as well. Novel treatment approaches incorporating new ir- radiation techniques and novel drugs that might cross blood-brain barrier are urgently needed to change the faith of this still deadly disease. Several targeted agents have been introduced into clinical trials in SCLC, including matrix metalloproteinase inhibitors, thalidomide, and vaccines, with nega- tive results being more commonly reported than positive ones so far. Although initial attempts at targeted therapy in SCLC have been unsuccess- ful, several newly identified targets agents, such as anti-angiogenic strategies and Bcl-2 inhibitors, hold promise and are being tested in the ongoing clinical trials.28-30 Radiol Oncol 2012; 46(1): 54-59. In conclusion, the prognosis of patients with ex- tensive SCLS with brain metastases at the time of the diagnosis, suitable for specific chemotherapy and radiotherapy, does not seem to be significantly worse compared to the prognosis of patients with extensive SCLC without brain metastases. In exten- sive SCLC brain metastases might not represent a negative prognostic factor per se if they are treated appropriately. 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