Variability in biopsy quality informs translational research applications in hepatocellular carcinoma

Abstract

In the era of precision medicine, biopsies are playing an increasingly central role in cancer research and treatment paradigms; however, patient outcomes and analyses of biopsy quality, as well as impact on downstream clinical and research applications, remain underreported. Herein, we report biopsy safety and quality outcomes for percutaneous core biopsies of hepatocellular carcinoma (HCC) performed as part of a prospective clinical trial. Patients with a clinical diagnosis of HCC were enrolled in a prospective cohort study for the genetic, proteomic, and metabolomic profiling of HCC at two academic medical centers from April 2016 to July 2020. Under image guidance, 18G core biopsies were obtained using coaxial technique at the time of locoregional therapy. The primary outcome was biopsy quality, defined as tumor fraction in the core biopsy. 56 HCC lesions from 50 patients underwent 60 biopsy events with a median of 8 core biopsies per procedure (interquartile range, IQR, 7–10). Malignancy was identified in 45/56 (80.4%, 4 without pathology) biopsy events, including HCC (40/56, 71.4%) and cholangiocarcinoma (CCA) or combined HCC-CCA (5/56, 8.9%). Biopsy quality was highly variable with a median of 40% tumor in each biopsy core (IQR 10–75). Only 43/56 (76.8%) and 23/56 (41.1%) samples met quality thresholds for genomic or metabolomic/proteomic profiling, respectively, requiring expansion of the clinical trial. Overall and major complication rates were 5/60 (8.3%) and 3/60 (5.0%), respectively. Despite uniform biopsy protocol, biopsy quality varied widely with up to 59% of samples to be inadequate for intended purpose. This finding has important consequences for clinical trial design and highlights the need for quality control prior to applications in which the presence of benign cell types may substantially alter findings.

Techniques for Profiling the Cellular Immune Response and Their Implications for Interventional Oncology

“…It is important to understand the quality of tissue sample needed for different tests as the tissue requirements can vary from one molecular assay to another. A recent analysis of biopsies performed for 50 patients with hepatocellular carcinomas for genetic, proteomic, and metabolomic profiling were evaluated for the quality thresholds of the biopsy samples [ 292 ]. In total, 76.8% of the biopsies were found to be adequate for next-generation sequencing and 41.1% of the biopsies were found to be adequate for proteomic/metabolomic profiling [ 292 ].…”

“…A recent analysis of biopsies performed for 50 patients with hepatocellular carcinomas for genetic, proteomic, and metabolomic profiling were evaluated for the quality thresholds of the biopsy samples [ 292 ]. In total, 76.8% of the biopsies were found to be adequate for next-generation sequencing and 41.1% of the biopsies were found to be adequate for proteomic/metabolomic profiling [ 292 ]. The results of this study demonstrated the difficulty in obtaining adequate biopsies for complete profiling and the need for non-destructive point of care tests to confirm the adequacy of biopsies.…”

An Expanded Role for IRBs in the Oversight of Research Biopsies

“…27 Many biomarker studies are also never published and so have limited contributions to the advancement of science. 28 There is also variability in the quality of tissue collected in research biopsies, which limits their utility in answering scientific questions. 29 At NCI-designated cancer centers, clinical trials must undergo formal scientific review prior to IRB review.…”

“…Further, while there may be value to a single biopsy for molecular characterization, some studies seek multiple samples despite little evidence that serial biopsies generate critical scientific insights or impact drug development 27 . Many biomarker studies are also never published and so have limited contributions to the advancement of science 28 . There is also variability in the quality of tissue collected in research biopsies, which limits their utility in answering scientific questions 29 .…”

Towards accesible brain-tumor classification at the point of care: Nanopore methylation sequencing from Formalin-Fixed Paraffin-Embedded (FFPE) pathology samples

“…Currently, most health centres can only provide Formalin-Fixed Paraffin-Embedded (FFPE) samples due transport and storage limitations 8,16 . Additionally, the unknown tumor fraction in FF samples poses a degree of uncertainty, since a low tumor fraction in the homogonized sample limits classification 17 . In FFPE samples, histopathological staining can be performed, so the tumor fraction is not only known but can be selectively enriched for analysis 18 .…”