Small cell lung cancer (SCLC) remains one of the most lethal malignancies and a major health riddle. The therapeutic options are limited. The combination of etoposide or irinotecan with platinum chemotherapy is the standard of care at any stage. The last decade systemic efforts have been done to reveal specific therapeutic targets for small cell lung carcinomas. In this review, we focus on the new therapeutic strategies of SCLC, including immune-related treatment that may change the prognosis of the disease. The main genetic mutations observed in SCLC are TP53 and RB1 mutations; however, it is well known that these molecules are not yet targetable. In recent years, research has revealed other frequent genetic alterations and activated signaling pathways that might be an effective treatment target. Loss of PTEN, activating PI3K mutations, inhibition of NOTCH pathway and aurora kinase activation are among them. Moreover, FDGFR1 amplification, activation of the Hedgehog pathway and repair-protein PARP1 seem to participate in SCLC tumorigenesis. These new findings have identified some interesting targets. Moreover, immunotherapy tries to find its place in the treatment of SCLC. Immune checkpoint inhibitors are under investigation in phase I to III clinical trials. We hope that in next years the treatment of SCLC patients will be improved with the administration of targeting therapy and the introduction of immunotherapy.

Lung well-to-moderately differentiated neuroendocrine tumors (also known as carcinoids) and large cell neuroendocrine lung carcinoma (poorly differentiated neuroendocrine tumor) are rare neuroendocrine neoplasms, which account for less than 4% of all lung neoplasms. Due to their low incidence, their systemic treatment is greatly influenced by therapeutic evidence derived from the more frequent gastroenteropancreatic neuroendocrine neoplasms and/or small cell lung carcinoma leading to significant bias. Currently, employed systemic therapies for lung carcinoids, aiming at controlling tumor growth include long acting somatostatin analogues (SSAs), peptide receptor radionuclide therapy, chemotherapy and molecular-targeted therapy. In this review, each of those treatments is presented based upon available clinical evidence from retrospective and prospective studies particularly focused on the role of everolimus in the advanced setting and on ongoing clinical trials reflecting our expectations in the near future. In addition, we critically analyse currently employed treatment of large cell neuroendocrine carcinoma where the appropriate chemotherapeutic regimen is still a matter of debate.

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Background: Novel therapeutic approaches and new compounds during the last decade have prolonged survival of breast cancer patients with metastatic disease, resulting in higher incidence of central nervous system (CNS) metastases. Many of these patients live longer than expected. Patients and methods: We reviewed breast cancer patients with brain metastases from our department, living longer than 1 year. Our purposes were to present patient and treatment characteristics and correlate them with disease outcome. Moreover, we aimed at reviewing the current literature. Results: We detected 20 women with brain metastases from breast cancer, living longer than 1 year. The mean age was 41 years (range 22-61 years). One (5%) woman had luminal A breast cancer type, four (20%) patients had luminal B and HER2 negative, nine (45%) patients luminal B and HER2 positive, four (20%) patients HER2 enriched and two (10%) patients had triple-negative breast cancer. Most of them (70%) had infiltrating ductal histological type and grade 3. Moreover, the majority had known metastatic disease when brain metastases appeared. The most common sites of disease were lung, liver and bone. Median time from breast cancer diagnosis until the presence of CNS metastases was 44 months (range 6-204 months). The progression free survival (PFS) of the most chemotherapeutic schedules was according to the literature. However, PFS of some compounds exceeded all expectations. Median time of survival was 25 months (range 13-116 months). Ten patients are still alive, having achieved a median survival rate of 35 months (range 17-78 months). Conclusion: The combination of surgery, radiotherapy, chemotherapy and anti HER2 treatments is at present the best way to extend the OS and improve the quality of life of breast cancer patients with brain metastases. Prognostic markers for assessing brain metastases are required. Application of prophylactic treatment for these patients is under consideration.