(P 120) THE DIAGNOSTIC AND PROGNOSTIC VALUE OF PLASMA SMALL EXTRACELLULAR VESICLES PHENOTYPE IN PATIENTS WITH GASTROINTESTINAL STROMAL TUMOUR

Objective: In patients with Gastrointestinal Stromal Tumour (GIST), the tumour size, tumour location, mitotic count [1], as well as the KIT and PDGFRA mutational status [2] are known prognostic factors. However, a soluble diagnostic or prognostic biomarker does not exist. The objective of this study was to investigate the diagnostic and prognostic value of small extracellular vesicles’ (SEVs) phenotype in patients with Gastrointestinal Stromal Tumour (GIST).

Methods: GIST patients from the two sarcoma centres in Denmark were included from January 2019 to December 2021. Patients in the oncological departments were included independent of disease- and treatment status. Patients were divided into three groups; group 1: patients undergoing radical surgery, group 2: patients with local, locally advanced, or metastatic GIST, and group 3: patients without disease (Fig. 1). The blood samples from patients undergoing surgery were collected pre and postoperative, while the blood samples from the patients receiving systemic treatment or in follow-up after systemic treatment were collected at inclusion and image verified progression or relapse. Protein microarray technology was used for the SEV analysis, investigating 31 surface- or surface associated antigens with a known relation to cancer. The primary endpoint of the study was the progression of GIST as per Response Evaluation Criteria in Solid Tumours 1.1. The Kruskal-Wallis H test was used for the one-way analysis of variance between different groups of patients. We accepted a 0.05 significance level since this is an explorative and hypothesis-generating study. We used Harrell’s C statistics, Akaike information criterion, Bayesian information criterion, and the likelihood ratio to find the best-suited prognostic profile of SEV markers. The date for cut-off for data analysis was the 30th of March 2022.

Results: A total of 157 patients were included, 15 patients in group 1, 125 patients in group 2, and 17 patients in group 3. Patient and disease characteristics are summarized in Table 1. The median follow-up time was 2.05 years. In group 2, 31 of 125 patients progressed. By comparing group 2 and the postoperative samples of group 1, the SEV level of CD42a was diagnostic for GIST (p=0.008). In group 2, Carcinoembryonic Antigen (CEA) and Glucose Transporter 1 (GLUT-1) were found to be prognostic. In both the uni- and multivariate analysis GLUT-1 and CEA were found to be significant (univariate analysis; GLUT-1: HR=0.46, 95% CI 0.22-0.97, p=0.041; CEA: HR=2.18, 95% CI 1.04-4.55, p=0.039). Composing a profile consisting of CEA and GLUT-1 adjusted for age at inclusion was found to have a prognostic value (HR=5.10, 95% CI 2.38-10.93, p< 0.0001), Fig. 2.

Conclusion: This is the first study investigating the phenotype of SEVs in patients with GIST and showed that the plasma SEV level of CD42a might be of diagnostic value while CEA and GLUT-1 might be of prognostic value.

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