Therapeutic approach to brain metastasis in high-grade neuroendocrine carcinomas of the lung: where do we stand?

Abstract

High-grade neuroendocrine carcinomas (HGNECs) of the lung represent a heterogeneous group of poorly differentiated neoplasms and include large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC). The development of brain metastases (BMs) occurs in roughly 20% of patients at diagnosis and represents a major issue in the management of HGNECs. The aim of this review is to briefly summarize current knowledge on the therapeutic options to treat lung HGNECs-derived BMs touching upon the unsolved issues of current treatment approaches and the future perspectives in the management of CNS-metastatic HGNECs of the lung. We searched MEDLINE and OVID databases for articles in English published from January 1980 to September 2016. SCLCs and LCNECs share clinical characteristics and biological behavior, as well as major genetic alterations. Consistently, SCLC-like chemotherapy appears to be more effective in LCNECs as compared to NSCLC-like regimens. However, the role of transthoracic radiotherapy and prophylactic cranial irradiation (PCI) is much less studied in LCNECs. Available data might suggest to approach LCNECs patients in a similar way to SCLCs also when it comes to thoracic radiotherapy and PCI. The development of brain metastasis is associated with poor prognosis and shortened survival in patients with HGNECs. Conventional cytotoxic agents display limited efficacy against HGNECs-derived brain metastasis. Patient with limited or extensive SCLC who respond to chemotherapy benefits from PCI. In LCNECs, the use of PCI is not well defined and might potentially improve the outcome of these patients. Prospective clinical trials addressing this issue are urgently needed.