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. 2024 Dec 20;16(24):4252.
doi: 10.3390/cancers16244252.

The Safety and Suitability of DNA Sequencing of Tissue Biopsies Performed on Patients Referred to a Phase I Unit

Angela Esposito  1 , Edoardo Crimini  1   2 , Carmen Criscitiello  1   2 , Carmen Belli  1 , Roberta Scafetta  1   3 , Raimondo Scalia  1   4 , Grazia Castellano  1   2 , Elisa Giordano  1   2 , Jalissa Katrini  1   2 , Liliana Ascione  1   2 , Luca Boscolo Bielo  1   2 , Matteo Repetto  1   2 , Antonio Marra  1 , Dario Trapani  1   2 , Gianluca Maria Varano  5 , Daniele Maiettini  5 , Paolo Della Vigna  5 , Franco Orsi  5 , Elena Guerini Rocco  2   6 , Nicola Fusco  2   6 , Giuseppe Curigliano  1   2
Affiliations

The Safety and Suitability of DNA Sequencing of Tissue Biopsies Performed on Patients Referred to a Phase I Unit

Angela Esposito et al. Cancers (Basel). .

Abstract

Background: Early-phase clinical trials offer a unique opportunity for patients with cancer. These trials often mandate biopsies to collect tumor tissue for research purposes, requiring patients to undergo invasive procedures. Some trials mandate molecular prescreening, but the success of these analyses relies on the quality and quantity of the tested materials. Additionally, bioptic procedures may result in complications.

Methods: We retrospectively examined the records of patients referred to the Early Drug Development (EDD) Unit of the European Institute of Oncology who underwent biopsies for research purposes between January 2014 and December 2022. Our objective was to assess the safety of biopsy procedures and adequacy of the samples for NGS testing.

Results: In total, 355 out of 731 patients (48.6%) underwent protocol-mandated biopsies. The most frequent sites of biopsy were the liver, lymph nodes, skin, and breast. Histological diagnosis was achieved in 349 (98%) patients, and NGS testing was successfully conducted in 111/127 (88.4%) cases. Of the 16 unsuccessful NGS attempts, 9 were performed on liver tissue. Unsuccessful NGS testing was attributed to poor sample quality and/or quantity, and the success rate varied significantly based on the specific tests attempted. Complications occurred in a small proportion of patients (4.8%), and none were serious.

Conclusions: The non-negligible failure rate of NGS testing highlights the crucial need for implementing specific guidelines and Standard Operating Procedures for samples intended for NGS. With the use of a risk-based biopsy framework to guide clinical decisions, procedure-related complications may be minimized.

Keywords: agnostic therapy; biomarker; biopsy; cancer; drug development; next-generation sequencing; phase I trials; precision oncology; real world; targeted therapies.

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Conflict of interest statement

A.M. has received honoraria as a consultant, an advisor, or a speaker from Roche and Menarini/Stemline and has received support for travel and accommodation from AstraZeneca. G.C. reports personal fees from Daichii Sanlyo, Astra Zeneca, Gilead, Lilly, Pfizer, Novartis, Menarini, Roche, Exaxt Sciences, and BluePrint outside the submitted work. E.G.R. has relevant relationship (advisory fees, honoraria, travel accommodation and expenses, grants, and non-financial support) with AstraZeneca, Exact Sciences, GlaxoSmithKline (GSK), Novartis, Roche, and Thermo Fisher Scientific unrelated to the current work. N.F. has received honoraria for consulting, advisory role, speaker bureau, travel, and/or research grants from Merck Sharp & Dohme (MSD), Novartis, AstraZeneca, Roche, Menarini, Daiichi Sankyo, GlaxoSmithKline (GSK), Gilead, Diaceutics, Adicet Bio, Sermonix, Reply, and Leica Biosystems. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Circular grouped and stacked barplot: bars represent the sites of biopsy, grouped by primary tumors (showed inside the circle: Breast, breast cancer; Chol, cholangiocarcinoma; Other, other tumor types). Only tumors that counted at least 5 NGS attempts are reported separately from “Other”. The height of the bars corresponds to the number of biopsies performed at the anatomic site in the specific tumor type. Bars of stacked colors represent the number of each NGS test (see legend). Donut plots report the success rate of each NGS test for the biopsy site and primary tumor. The inner, middle, and outer circles represent other tests, GerSom and Foundation OneTM, respectively. The color of each test is consistent with the circular barplot. The proportion of failures for each test is reported in red. The tables provide the corresponding data.
Figure 2
Figure 2
Schematization of study population and adverse events associated with biopsies. * Biopsies for which NGS results are available.
See this image and copyright information in PMC

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