Sequenced circulating tumor (ct) DNA to detect the molecular landscape in advanced GIST.

Abstract

11036 Background: Molecular (mol) characteristics-guided precision therapy has well-established utility in GIST management. The GIST mol landscape is poorly represented by selective tumor biopsy (bx) material, especially in metastatic and treatment-refractory GIST. ctDNA can overcome some of the limitations of selective tissue bx specimens and provide comparable or greater mol information. ctDNA represents an emerging mol biomarker in advanced (adv) GIST. Methods: Next generation sequencing analyses (MSK-IMPACT or custom-capture GIST specific panel) were performed on ctDNA prospectively collected from patients (pts) with adv GIST. MSK-IMPACT was performed on tumor material (archival tissue or paired tissue bx specimens taken in parallel with ctDNA collection from clinical trial participants). The primary objective was to determine the concordance between the mol landscape of GIST identified by sequenced tumor tissue versus ctDNA. Secondary objective was to correlate characteristics of sequenced ctDNA with standard measurements of response assessment. Results: 47 ctDNA samples collected from 25 pts with adv GIST were sequenced using MSK-IMPACT ( > 400 genes). MSK-IMPACT was performed on archival tumor material. Sequenced ctDNA detected the mutational spectrum of tumor tissue in 48% of cases. In 50% of these cases, ctDNA identified novel treatment-resistance mutations not previously identified in the archival tissues. To optimize sensitivity of detection, a custom-designed GIST specific ctDNA sequencing panel was developed incorporating 19 of the most commonly altered genes observed from MSK-IMPACT analysis performed on > 75 imatinib-refractory adv GIST tumor samples. 52 ctDNA samples collected from 30 pts with paired tumor bx samples have been sequenced using the custom-capture GIST panel. The tumor bx samples have been sequenced using MSK-IMPACT. Results are pending and will be presented. A separate cohort of ctDNA samples serially collected in the setting of a prospective clinical trial are being sequenced. The mol results with correlated treatment response by RECIST will also be presented. Conclusions: ctDNA could detect a broad spectrum of mol heterogeneity and potentially be used as a biomarker to guide precision therapy in adv GIST. Further research is necessary to determine the optimal ctDNA sequencing assay and the appropriate clinical setting to utilize in GIST.