Data from Tumor Genotype Is an Independent Prognostic Factor in Primary Gastrointestinal Stromal Tumors of Gastric Origin: A European Multicenter Analysis Based on ConticaGIST

<div>Abstract<p><b>Purpose:</b> Although the mutational status in gastrointestinal stromal tumors (GIST) can predict the response to treatment with tyrosine kinase inhibitors, the role of tumor genotype as a prognostic factor remains controversial. The ConticaGIST study sought to determine the pathologic and molecular factors associated with disease-free survival (DFS) in patients with operable, imatinib-naive GIST.</p><p><b>Experimental Design:</b> Clinicopathologic and molecular data from 1,056 patients with localized GIST who underwent surgery with curative intention (R0/R1) and were registered in the European ConticaGIST database were prospectively obtained and reviewed. Risk of tumor recurrence was stratified using the modified NIH criteria. The median follow-up was 52 months.</p><p><b>Results:</b> On testing for potential prognostic parameters, the following were associated with inferior DFS on multivariable Cox model analysis: primary nongastric site, size >10 cm, mitotic index >10 mitoses per 50 high power field, and the <i>KIT</i> exon 9 duplication [hazard ratio (HR), 1.47; 95% confidence interval (CI), 0.9–2.5; <i>P</i> = 0.037] and <i>KIT</i> exon 11 deletions involving codons 557 and/or 558 [<i>KIT</i>del-inc557/558; HR, 1.45; 95% CI, 1.0–2.2; <i>P</i> = 0.004]. Conversely, <i>PDGFRA</i> exon 18 mutations were indicators of better prognosis [HR, 0.23; 95% CI, 0.1–0.6; <i>P</i> = 0.002]. <i>KIT</i>del-inc557/558 were an adverse indicator only in GIST localized in the stomach (<i>P</i> < 0.001) but not in tumors with nongastric origin. In gastric GIST, all other mutations presented remarkably superior 5-year DFS.</p><p><b>Conclusions:</b> In conclusion, tumor genotype is an independent molecular prognostic variable associated with gastric GIST and should be used for optimizing tailored adjuvant imatinib treatment. <i>Clin Cancer Res; 20(23); 6105–16. ©2014 AACR</i>.</p></div>