Genotype of Primary Gastrointestinal Stromal Tumors Predicts Outcome
Last Updated on October 19, 2014 by Joseph Gut – thasso
October 19, 2014 – The following article originates from Reuters Health Information staff via Medscape. Copyright with the respective holders. Here the article:
The genotype of primary gastrointestinal stromal tumors (GIST) of gastric origin can be used to predict the risk of relapse and, thereby, identify patients for adjuvant therapy with imatinib, according to an analysis of a European database.
Many patients with GIST can be cured by surgery alone, but as many as half will eventually relapse. Adjuvant imatinib therapy is a
widely accepted treatment standard in patients at higher risk of relapse, but how to identify these patients remains uncertain.
Dr. Maria Debiec-Rychter from KU Leuven and University Hospitals in Leuven, Belgium and colleagues used data from 1056 patients in the ConticaGIST registry to assess the role of the tumor KIT and PDGFRA genotype, along with other prognostic factors.
During a median 52 months’ follow-up (range, 1-304 months), 34.9% had progressive disease with a median disease-free survival (DFS) of 17.6 months (range, 1-252 months), the authors reported October 7th online in Clinical Cancer Research.
Tumor genotype KIT exon 9 and KITdel-inc557/558 increased the risks of tumor progression by 47% and 45%, respectively, while PDGFRA exon 18 mutations were associated with a 77% lower risk of tumor progression. Unlike KIT exon 9 and PDGFRA exon 18 mutations, KITdel-inc557/558 only influenced prognosis in patients with GIST localized in the stomach.
The relapse rate five years after surgery among patients with gastric GIST was more than twice as high in those harboring KITdel-inc557/558 as in those with other KIT exon 11 mutations (61% vs 29%). Even in tumors classified as non-high risk and originating from the stomach, the presence of KITdel-inc557/558 remained an important predictor of poor outcome in comparison with other KIT exon 11 mutations, KIT exon 9, and PDGFRA exon 18 mutations.
“Our results underscore the importance of routine genotyping for an optimal management of GIST, either in the adjuvant or advanced disease setting,” the investigators conclude. “Evaluation of tumor genotype has especially prognostic value in GIST of gastric origin.”
“Our findings contribute to the identification of a subset of localized gastric GIST patients with higher risk of relapse irrespectively of standard clinical prognostic factors,” they add. “The presence of a KITdel-inc557/558 mutation could be used as an additional parameter for more accurate selection of patients for adjuvant therapy.”
Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.