FP07.14 Implementation of a Lung Biopsy Histology Protocol Supports Successful Cancer Biomarker Testing

Abstract

Non-small cell lung cancer (NSCLC) management increasingly relies on biomarker testing, which presents a logistical challenge for utilization of lung biopsy specimens beyond routine diagnosis. Appropriate allocation of tissue from small biopsies is critical in order to permit for accurate histologic diagnosis while preserving tissue for ancillary studies such as PD-L1 testing and next generation sequencing (NGS). International surveys show that satisfaction with molecular testing is less than ideal, driven in part by inadequacy of formalin-fixed paraffin embedded (FFPE) tumor tissue for biomarker testing in over a quarter of clinical cases by some reports. We developed a histology protocol (LUNGCOR) that generates multiple unstained FFPE slides up front in order to increase tissue yields for pathologic diagnosis and ancillary testing. We examined the efficacy of this protocol in regards to molecular testing success rates. Biopsy samples (e.g. transbronchial or fine needle biopsies) were flagged for the LUNGCOR protocol based on a clinical indication of "lung mass" or need for genomics. Proceduralists were requested to prospectively specify when samples were obtained for the purposes of biomarker testing. Per protocol, after embedding, 2 H&E slides with 18 intervening 4-micron unstained FFPE slides were prepared and reserved for immunohistochemistry or molecular studies. We performed a retrospective review of consecutive LUNGCOR specimens within the pathology information system and electronic medical record to determine the usage patterns for the unstained slides and success rates of molecular testing. This analysis is restricted to the first 2 years (2015-2016) following protocol initiation. 300 specimens were designated for the LUNGCOR protocol in this time period. Of these specimens, 84% resulted in a malignant diagnosis and 175 (58%) were non-squamous NSCLC. Of these, 87 (50%) of NSCLC underwent molecular profiling of some kind, either in house NGS, single gene PCR assays, or send-out NGS. For cases undergoing in house next generation sequencing (447-gene panel), 61 of 69 (88%) cases generated complete genotyping for all required and emerging biomarkers for targeted therapy. Sequencing failures were most commonly due to inadequate tumor content in the biopsy specimen, rather than inadequate size of the overall sample. Generation of unstained slides during upfront histologic processing of known or suspected NSCLC increases availability of tissue for molecular testing and reduces risk of sample inadequacy due to specimen loss during routine handling steps, such as "refacing" the block. This straightforward process improvement can improve the yield of invasive biopsies for essential biomarker testing and contribute to improved patient outcomes.