Selection of Chemotherapy in Advanced Poorly Differentiated Extra-Pulmonary Neuroendocrine Carcinoma

Abstract

Extra-pulmonary poorly differentiated neuroendocrine carcinoma is rare, and evidence for treatment has been limited. In this article, the evidence behind the cytotoxic chemotherapy choices used for metastatic or unresectable EP-PD-NEC is reviewed. In the first-line setting, etoposide and platinum chemotherapy or irinotecan and platinum have been demonstrated to be equivalent in a large phase III trial. Questions remain regarding the optimal number of cycles, mode of delivery, and the precise definition of platinum resistance in this setting. In the second-line setting, FOLFIRI has emerged as an option, with randomized phase 2 trials demonstrating modest, but significant, response rates. Beyond this, data are extremely limited, and several regimens have been used. Heterogeneity in biological behaviour is a major barrier to optimal EP-PD-NEC management. Available data support the potential role of the Ki-67 index as a predictive biomarker for chemotherapy response. A more personalised approach to management in future studies will be essential, and comprehensive multi-omic approaches are required to understand tumour somatic genetic changes in relation to their effects on the surrounding microenvironment.

Prognostic Evaluation of Piezo2 Channels in Mammary Gland Carcinoma

“…This marker reacts with cells that are not in G0 phase of the cell cycle, and is commonly used in clinical cancer histopathology to assess the proliferation index [36][37][38]. For example, Ki67 proliferation index is determinant in GIST [39] and neuroendocrine tumors [40,41]. Moreover, it is a valuable prognostic factor in other tumors like gliomas [42], lymphoma [43], sarcomas [44], melanoma [45] or carcinomas [46][47][48].…”