Abstract 463: Features consistent with a small-cell neuroendocrine like (SC/NE-L) transformation can be readily detected and quantified in circulating tumor cells (CTCs)

Abstract

Abstract Background: The increasing availability and earlier use of life prolonging drugs targeting the androgen receptor signaling axis (ARSI) has resulted in an increase in the frequency of late state tumors with “small cell/neuroendocrine like (SC/NE-L) phenotypes” similar to small-cell lung cancer (SCLC). These tumors are typically heterogenous wherein the small-cell component represents only a portion of CTC's present. Definitive pathologic criteria to diagnose small-cell neuroendocrine transformation are lacking, and the eligibility criteria across trials in this space inconsistent, limiting the ability to relate outcomes between studies. We hypothesize that an analytically validated assay for a rigorously defined “small-cell CTC” phenotype would clarify the identification and diagnosis of SC/NE-L tumors. Methods: Using the WHO guidelines for small-cell diagnosis in tissue as reference, we defined an equivalent set of single-cell criteria for defining a CTC with small cell or neuroendocrine like (SC/NE) histology that include: a circulating CD45- cell with a high nuclear to cytoplasm area ratio, small size, high circularity, lack of detectable nucleoli, salt and pepper chromatin, SC/NE or tumor-related protein expression (DLL3, CD56, CK etc.), and other features associated with lineage plasticity (i.e., CK speckling). Clinical feasibility of feature extraction was explored on CTCs detected using the Epic Sciences platform in the blood of patients with small-cell lung and late state prostate cancers. Results: Using the Epic Sciences platform, morphologic features associated with small-cell or neuroendocrine transformation can be readily identified and quantified automatically in CTCs in a liquid biopsy from patients with small-cell lung and prostate cancers. Conclusions: Identifying small-cell to neuroendocrine like (SC/NE-L) CTC subtypes may aid in establishing that lineage transformation to a SC/NE-L phenotype has occurred where invasive single site tissue biopsies may not be informative or feasible. Citation Format: Howard I. Scher, Adam Jendrisak, Cole Gilbertson, Audrey Gill, Ethan Barnett, Anuradha Gopalan, Niamh Keegan, Samir Zaidi, Hannah Benoliel, Carbone Emily, Eva Wang, James Lu, Alisa Tubbs, Amanda Anderson, Joshua Jones, Joseph D. Schonhoft, Rick Wenstrup. Features consistent with a small-cell neuroendocrine like (SC/NE-L) transformation can be readily detected and quantified in circulating tumor cells (CTCs) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 463.