Faglig bidrag på internasjonale møter og konferanser
CTOS 2018Muntlig presentasjon:
NON-INVASIVE DETECTION OF CTDNA REVEALS INTRATUMOR HETEROGENEITY AND IS ASSOCIATED WITH TUMOR BURDEN IN GASTROINTESTINAL STROMAL TUMOR
Boye Kjetil1; Heidi Namløs2; Skyler J. Mishkin3; Tale Barøy2; Susanne Lorenz4; Bodil Bjerkehagen5; Eva Stratford2; Else Munthe2; Brian A. Kudlow3; Ola Myklebost2; Leonardo A. Meza-Zepeda2
1Department of Oncology, Oslo University Hospital, Oslo, Norway; 2Department of Tumor Biology, Oslo University Hospital, Oslo, Norway; 3Archer DX, Inc., Boulder, CO, USA; 4Genomics Core Facility, Oslo University Hospital, Oslo, Norway; 5Department of Pathology, Oslo University Hospital, Oslo, Norway
Molecular analysis of circulating tumor DNA (ctDNA) has a large potential for clinical application by capturing tumor-specific aberrations through non-invasive sampling. In gastrointestinal stromal tumor (GIST), analysis of KIT and PDGFRA mutations is important for therapeutic decisions, but the invasiveness of traditional biopsies limits the possibilities for repeated sampling. The objective of the present study was to explore the clinical utility of ctDNA in GIST.
Circulating cell-free DNA was isolated from plasma from 50 GIST patients. Targeted next-generation sequencing was performed using the Archer Reveal ctDNA 28 kit for Illumina, and data was processed using the Archer Analysis (v5.1) pipeline. Associations between ctDNA detection and clinical and histopathological parameters were analyzed.
Tumor-specific mutations in ctDNA were detected in 16 of 44 plasma samples (36%) from treatment-na ve patients, and in 3 of 6 (50%) patients treated with tyrosine kinase inhibitors. A significant association between detection of ctDNA and the modified National Institutes of Health risk classification was found. All patients with metastatic disease had detectable ctDNA. Tumor burden was the most important detection determinant in localized disease. Median tumor size was 13.4 cm for patients with detectable mutation in plasma compared to 4.4 cm in patients without detectable mutation (p=0.006). ctDNA analysis of a patient with disease progression on imatinib revealed that multiple resistance mutations were synchronously present, and detailed analysis of tumor tissue showed that these were spatially distributed in the primary tumor, revealing a high degree of intratumor heterogeneity. Plasma samples taken throughout the course of treatment demonstrated that clonal evolution can be monitored over time.
We have shown that detection of GIST-specific mutations in plasma is particularly feasible for patients with high tumor burden. In such cases, mutational analysis by use of liquid biopsies can capture the molecular heterogeneity of the whole tumor, and may guide treatment decisions during progression. Analyses of repeated samples from a cohort of patients with metastatic GIST are ongoing.
CIRCSARC; NON-INVASIVE MONITORING OF SARCOMAS PATIENTS BY CIRCULATING TUMOUR DNA IN PLASMA
Heidi M. Namløs1; Seyed Hossein Moosavi1; Bodil Bjerkehagen2; Olga Zaikova3; Susanne Lorenz4;
Lars Aasheim4; Eivind Hovig1; Nina L. Jebsen5; Ola Myklebost6; Boye Kjetil7; Leonardo A. Meza-Zepeda1
1Department of Tumor Biology, Oslo University Hospital, Oslo, Norway; 2Department of Pathology, Oslo University Hospital, Oslo, Norway; 3Department of Surgery, Oslo University Hospital, Oslo, Norway; 4Department of Core Facilities, Oslo University Hospital, Oslo, Norway; 5Department of Oncology, Haukeland University Hospital, Bergen, Norway; 6Department of Clinical Science, University of Bergen, Bergen, Norway; 7Department of Oncology, Oslo University Hospital, Oslo, Norway
THE RELATIONSHIP BETWEEN POSITIVE RESECTION MARGINS, TUMOUR RUPTURE AND PROGNOSIS IN GASTROINTESTINAL STROMAL TUMOUR. A POPULATION-BASED ANALYSIS
Toto Hølmebakk1; Bodil Bjerkehagen2; Ivar Hompland3; Stephan Stoldt1; Boye Kjetil3
1Dept. of Abdominal Surgery, Oslo University Hospital, Oslo, Norway; 2Dept. of Pathology, Oslo University Hospital, Oslo, Norway; 3Dept. of Oncology, Oslo University Hospital, Oslo, Norway
A SCANDINAVIAN POINT OF VIEW
-CARING FOR PATIENTS WITH SARCOMA ACROSS BOUNDARIES
Stine Naess1; Charlott Vaade1
1.Department of Early Cancer Trials and Research Support, Oslo University Hospital, Oslo, Norway.
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