Utility of Circulating Tumor DNA in the Management of Patients With GI Stromal Tumor: Analysis of 243 Patients.
retrospective_cohort · Level III
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- Also identified by DOI 10.1200/PO.19.00253.
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Abstract
GI stromal tumor (GIST) is the most common sarcoma of the GI tract. Management of patients with GIST is determined by <i>KIT</i>, <i>PDGFRA</i>, or other genomic alterations. Tissue-based next-generation sequencing (NGS) analysis is the standard approach for diagnosis, prognosis, and treatment selection. However, circulating tumor DNA (ctDNA)-based NGS is a novel and noninvasive alternative. ctDNA sequencing results were evaluated in blood samples from 243 de-identified patients within the Guardant360 database. Under an approved institutional review board protocol, a retrospective analysis was performed on 45 single-institution patients. Of 243 patients, 114 (47%) were women, and the median age was 59 years (range, 17-90 years). Patients with no alterations and variations of uncertain significance were excluded. Of the 162 patients with known pathogenic mutations, <i>KIT</i> was the most common (56%), followed by <i>NF</i> (7%), <i>PDGFRA</i> (6%), <i>PI3KCA</i> (6%), <i>KRAS</i> (5%), and others (6%). Most tumors harbored an actionable <i>KIT</i> or <i>PDGFRA</i> mutation. Our institutional cohort (n = 45) had 16 (35%) <i>KIT</i> exon 11 mutations, 3 (6%) <i>KIT</i> exon 9 mutations, and 1 (2%) <i>PDGFRA</i> mutation detected on ctDNA. Resistance mutations were observed in <i>KIT</i> exon 17 (8 patients), exon 13 (3 patients), and in both (3 patients). Our comparison of ctDNA with tissue NGS revealed a positive predictive value (PPV) of 100%. Failure of concordance was observed in patients with localized or low disease burden. From the time of ctDNA testing, the median overall survival was not reached, whereas the median progression-free survival was 7 months. ctDNA provides a rapid, noninvasive analysis of current mutations with a high PPV for patients with metastatic GIST. ctDNA-based testing may help to define the optimal choice of therapy on the basis of resistance mutations and should be studied prospectively.