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Neuroendocrine neoplasms are classified as epithelial and non-epithelial based on their origin being from epithelial neuroendocrine progenitor cells or derived from the neural crest. The latter are negative for cytokeratin (hence non-epithelial) and mostly result from neoplastic transformation of paraganglia. Here, we are reviewing the most important histologic and immunophenotypic characteristics of neuroendocrine carcinomas as well as the current WHO classification guidelines. The terminology of neuroendocrine neoplasms is confusing due to various classification systems employed for each internal organ. In the lung and GI tract, for example, “neuroendocrine tumors” comprise carcinomas of different degree of differentiation and histologic grade. While in the lung the term refers strictly to low-grade neuroendocrine carcinomas, in the GI tract it comprises both low- and high-grade neuroendocrine carcinomas. Despite concerted efforts to unify the overall classification of neuroendocrine carcinomas across organs, major differences continue to persist.

PURPOSE To examine outcomes in patients undergoing linear accelerator (LINAC) based fractionated stereotactic radiosurgery (fSRS) to 30 Gy in 5 fractions. METHODS We completed a retrospective review of patients with brain metastases treated with 5-fraction LINAC fSRS at Phelps Health. All patients with CNS metastatic disease treated with fSRS were included in the study. Incidence of symptomatic radionecrosis (sRN), local brain failure (LBF), time to death, target volume and dose, prior whole brain radiotherapy (WBRT), prior surgical resection, and concurrent immunotherapy were assessed. sRN was defined as grade 2 or higher per CTCAE v4.0. RESULTS From 2016–2019, 28 patients and 60 lesions were treated. The most common metastasis histology was non-small cell lung cancer (n = 22), renal cell carcinoma (n = 12), and melanoma (n = 11). Median follow-up time was 6.49 months (range 0.33 – 23.96). Of 60 lesions, three lesions developed sRN and one asymptomatic patient developed radiographic evidence of radiation necrosis. Mean GTV was 1.03cm3 in patients with sRN. Of 57 lesions without sRN, median GTV was 1.45cm3 (range 0.11 - 20.1). Mean time to sRN was 3.17 months. Two symptomatic patients received prior WBRT. One symptomatic patient received concurrent immunotherapy. No symptomatic patients had surgical resection prior to fSRS. Among 24 lesions without prior radiation, 1 (4.2%) developed sRN. 10 lesions underwent surgical resection prior to fSRS with none developing sRN. 34 lesions were treated with concurrent immunotherapy and one developed sRN (2.9%). Local failure occurred in 9 lesions (15%). Median time to death for all patients was 4.50 months (range 1.02 - 19.40). CONCLUSIONS fSRS to 30 Gy in 5 fractions has promising efficacy with low incidence of sRN in treatment of CNS metastatic disease. Further investigation is required to determine predictors in patient outcome.