Biology and Systemic Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors

In recent years, there have been important scientific advances in the biologic characterization of neuroendocrine neoplasms and in their treatment. This review will describe these scientific advances, the evolving systemic treatment approaches, and important topics to be addressed in future research.

Clinical validation of CTC subtype frequency to prognosis OS in mCRPC patients.

302 Background: CellSearch is an FDA cleared assay that enumerates intact CK+, DAPI+, CD45- cells via EpCAM capture. CTC number is prognostic for survival pre- and post- systemic therapy. These cells are a subset of confirmed genomically altered CTC’s in blood. We report the prognostic significance for OS in mCRPC of CTC subtypes not enumerated by CellSearch including apoptotic CTCs, CK- CTCs, small CTCs, and CTC clusters. Methods: 221 blood samples from 179 unique patients were collected from pts about to begin AR directed (n = 150) or taxane (n = 71) therapy for progressive CRPC. Samples were analyzed utilizing the Epic Sciences platform to enumerate traditional (CK+, abnormal morph), apoptotic (CK+, fragmented nuclei), CK- (CK-/abnormal morph), small (CK+, normal morph), and CTC clusters. Patients were followed for up to 2.3 yrs. Paired CellSearch and Epic traditional CTC counts were collected on 173 patient samples. Results: In paired analysis, Epic traditional CTCs were identified in 86% of patients vs. 67% by CellSearch, and any Epic CTC subtype was found in 96% of the patient samples. Increased frequency of any CTC subtype was a univariate predictor of OS (see table). Conclusions: Epic identified CTC subtypes not identified by CellSearch or other technologies that select or sort based upon size or epithelial expression. Cells were detected in 96% of the patient samples and all 5 subtypes were found to be prognostic for survival. The biologic characterization of CTC subtypes as a biomarker of drug sensitivity is ongoing. The increased clinical sensitivity of subtypes and prevalence of CTCs identified on the Epic platform provides a greatly expanded array of clinically relevant biomarkers to develop predictive liquid biopsy signatures in the metastatic setting. [Table: see text]