In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 2540-2540
Abstract:
2540 Background: There are different requirements of biopsies for diagnosis vs. pharmacologic evaluation of drug mechanism biomarkers. Evaluation of core needle biopsy pairs collected pre-dose and at a defined timepoint post-dose provides insight into the pharmacodynamics of agents in early development. Adequate biopsies are key for quantifying response of the tumor cell population to molecular drug action. Tumor heterogeneity and variable tumor content make many biopsy pairs unsuitable for biomarker evaluation with any assay platform (microscopy, immunoassay, etc.). We analyzed biopsies obtained from the Developmental Therapeutics Clinic (DTC) for suitability for PD assays. Methods: Specimens obtained from 2010-2016 across 4 trials were analyzed. For microscopy measurements, biopsy pairs collected using image guidance are snap-frozen, thawed under fixative, and embedded in paraffin with control tissues. The likelihood of finding optimal regions for analysis is maximized by preparing a series of sections with H & E stained flanking slides, and annotation by an anatomic pathologist. Results: Of 112 biopsies evaluated, 26% were found to contain 〈 5% tumor, making them inadequate for quantitative microscopy due to a mixture of factors, with the primary factor being predominantly non-neoplastic tissue, followed by extensive mucin content, necrosis, fibrosis, inadequate size and tissue artifact post-collection. Another 20% contained ≤25% tumor, and in this group, tumor segmentation methodology during image analysis increased the rate of evaluable biopsies. 56% of tissues had 〉 25% tumor and were suitable for analysis. Conclusions: Improved communication between oncologists, radiologists and pathologists is key to a better understanding of factors that affect suitability of biopsies for robust PD biomarker analyses. NCI’s DTC has implemented protocol modifications including increased tissue collection and frequent case reviews by the Phase 1 team, interventional radiologists and PD team aimed at understanding features during image guidance that relate to suitability. Implementation of a scoring system has allowed the assessment of suitability of biopsies for analysis. Funded by NCI Contract No HHSN261200800001E.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.2540
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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