Abstract 480: Biospecimen management for the serial measurement of molecular and architectural responses to therapy
Authors: Johnson Brett E. , Parmar Swapnil , Siex Kiara , Olson Anastasiya , Laverdure Jennifer , Keck Jamie , Kolodzie Annette , Guimaraes Alexander R. , Corless Christopher , Gray Joe , Mills Gordon , Bergan Raymond 
Published: August 2019

Rapid advances in molecular diagnostics have led to a growing need for sophisticated and adaptive biospecimen collection methodologies that employ careful acquisition, preservation, and allocation of limited biopsy tissue and blood specimens. To facilitate the comprehensive characterization of serial biospecimens from patients participating in real-time adaptive treatment precision medicine clinical trials, we designed a multi-omic and multi-imaging analytical platform and sought to maximize the quality and suitability of tissue for each downstream analytic. We optimized this biospecimen management system over 38 research-protocol driven biopsies on 33 patients with late stage metastatic breast, prostate, and pancreatic cancer. Importantly, no biopsy-related adverse events occurred. All tissue samples and derivatives therefrom were barcoded and tracked using a custom database built on the LabVantage platform. Here, we report successful strategies for coordination between medical and surgical oncology, interventional radiology, pathology, and clinical and research laboratories. We developed a biopsy prioritization schema that considers patient safety, site selection, procedure type, and amount of tissue required. We evaluated specimens from a variety of biopsy procedures, including radiologically-guided needle cores, as well as laparoscopic, video-assisted thoracoscopic, and excisional biopsies. Radiologically-guided biopsies using 18 gauge needles yielded a median of 5 (1 cm) cores with 70% tumor cellularity, and was the best substrate to rapidly allocate known quantities of tissue into a variety of preservation formats. We also examined enhanced biospecimen preservation methods that improved performance of downstream analytics. For example, optimization of the formalin fixation process included transferring tissue from bedside to formalin within 2 minutes, maintaining low temperature throughout fixation, and standardizing the time spent in formalin. These efforts resulted in recovery of higher quality RNA from FFPE blocks, less tissue required for RNA sequencing, and opened the door to immunofluorescent staining of phosphoproteomic markers. Our protocol uses several preservation methods, including: FFPE for immunohistochemical and cyclic immunofluorescent staining as well as targeted panel, whole exome, and transcriptomic sequencing; OCT freezing for multiple single cell sequencing methods; flash freezing for proteomic profiling; disaggregation of live cells for 2D and 3D culturing; and a specialized fixative for electron microscopy. In conclusion, we demonstrate the feasibility of collecting high quality biospecimens for a variety of downstream analytical platforms with diverse sample requirements. These methods can be used to comprehensively characterize limited amounts of valuable tissue in molecularly driven clinical trials.

Citation Format: Brett E. Johnson, Swapnil Parmar, Kiara Siex, Anastasiya Olson, Jennifer Laverdure, Jamie Keck, Annette Kolodzie, Alexander R. Guimaraes, Christopher Corless, Joe Gray, Gordon Mills, Raymond Bergan. Biospecimen management for the serial measurement of molecular and architectural responses to therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 480.