Pre-and Postoperative Circulating Tumour DNA in Patients With Gastrointestinal Stromal Tumour - A Methodological Assessment Study

Charlotte Margareta Brinch*, Ninna Aggerholm-Pedersen, Tim Svenstrup Poulsen, Wojciech Skovrider-Ruminski, Pieter DE Heer, Luit Penninga, Anders Krarup-Hansen, Estrid Hogdall

*Corresponding author af dette arbejde

Abstrakt

BACKGROUND/AIM: Gastrointestinal stromal tumours (GISTs) harbour genetic aberrations in receptor tyrosine kinase KIT (KIT) or platelet-derived growth factor receptor A (PDGFRA) in 85-90% of the patients. Circulating tumour DNA (ctDNA) is a potential biomarker in patients with GIST. Previous studies investigating ctDNA around surgery in patients with GIST presented divergent results regarding the proportion of patients with detectable ctDNA. This study aimed to 1) investigate the feasibility of detecting and monitoring ctDNA pre-and postoperative, 2) compare two different circulating free DNA (cfDNA) extraction methods, and validate results obtained by next-generation sequencing (NGS) using Real-Time PCR technology.

PATIENTS AND METHODS: Eight patients planned for immediate surgery or surgery after neoadjuvant oncological treatment were included in the study, from whom blood collection was performed pre- and postoperatively for ctDNA analysis. Furthermore, blood samples from six patients with GIST harbouring a point mutation in KIT or PDGFRA in tissues from primary tumours were used for comparison and validation sub-study.

RESULTS: In this explorative study, none of the patients with very low to intermediate risk GIST harboured KIT, or PDGFRA mutated ctDNA in pre-or postoperative blood samples. The methods used for cfDNA extraction gave similar output, and the two methods for ctDNA analysis gave identical results.

CONCLUSION: There is no benefit in analysing ctDNA around surgery in very low to intermediate-risk GIST patients. Larger studies investigating ctDNA in patients with high-risk GIST around surgery are warranted.

OriginalsprogEngelsk
TidsskriftAnticancer Research
Vol/bind42
Udgave nummer11
Sider (fra-til)5527-5537
Antal sider11
ISSN0250-7005
DOI
StatusUdgivet - nov. 2022

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