Abstract 3829: Genomic index is a strong predictor of metastatic outcome in intermediate gastrointestinal stromal tumors and an inclusion criteria for imatinib adjuvant therapy
Authors: Lartigue Lydia , Lagarde Pauline , Brulard Céline , Neuville Agnès , Rutkowski Piotr , Tos Paolo Dei , Waldermann Eva , Debiec-Rychter Maria , Italiano Antoine , Coindre Jean-Michel , Chibon Frédéric 
Published: May 2015

Gastrointestinal stroma tumors (GISTs) harboring a cKIT / PDGFRA activating mutation in 90% of cases benefit from the Imatinib mesylate (Glivec®) targeted therapy. Patients eligibility to imatinib adjuvant therapy is based, in Europe, on histological grading of tumor aggressiveness and no standard is currently available for tumor classified as intermediate risk (40% of patients).

We recently validated that genomic index (GI), a measure of the number and type of genomic copy number alterations, constitutes a strong predictor of clinical outcome in GIST, making it a possible prognostic factor for the intermediate GIST subgroup. To definitively clarify whether this genomic grading system would permit to categorize intermediate-risk patients into good and poor prognosis, we selected a cohort of 82 intermediate patients based on the Armed Forces Institute of Pathology (AFIP) classification and performed genomic profiling from formalin-fixed, paraffin-embedded (FFPE) samples using a microarray-based comparative genomic hybridization (array CGH) approach.

Data revealed that even if studied samples generally harbored a combination of the typical genetic aberrations found in GIST, i.e. 1p, 14q, 22q deletions and frequently lost CDKN2A locus on chromosome 9, they profoundly differed from each other on the total number of genomic changes and GI value, ranging, in the whole series, from 0 to 37 and 0 to 115.6, respectively. More interestingly, Kaplan-Meier analyses of metastatic-free survival unveiled that stratification of the tumors by the GI value at a cutoff of 10 (GI1&lt;10 and GI2&gt;10) separated the good (GI1) from the poor (GI2) prognosis patients (p&lt;10-3), undoubtedly proven that metastatic-risk in GIST intermediate patients is strongly associated with high GI values and genome complexity. In conclusion, GI is validated here as a robust marker to predict the clinical outcome of patients diagnosed with GIST and classified as intermediate by the current histologic method for risk assessment. Applicable in numerous Pathology Laboratories already using aCGH with FFPE samples for routine diagnostic tests, this assay currently stands as the best tool to determine which intermediate GIST-patients are likely to benefit from imatinib therapy and constitutes as such a novel advance in the clinical management of GISTs.

Citation Format: Lydia Lartigue, Pauline Lagarde, Céline Brulard, Agnès Neuville, Piotr Rutkowski, Paolo Dei Tos, Eva Waldermann, Maria Debiec-Rychter, Antoine Italiano, Jean-Michel Coindre, Frédéric Chibon. Genomic index is a strong predictor of metastatic outcome in intermediate gastrointestinal stromal tumors and an inclusion criteria for imatinib adjuvant therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3829. doi:10.1158/1538-7445.AM2014-3829