Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor: the ACOSOG Z9001 trial.

Published

Journal Article

PURPOSE:The ACOSOG (American College of Surgeons Oncology Group) Z9001 (Alliance) study, a randomized, placebo-controlled trial, demonstrated that 1 year of adjuvant imatinib prolonged recurrence-free survival (RFS) after resection of primary GI stromal tumor (GIST). We sought to determine the pathologic and molecular factors associated with patient outcome. PATIENTS AND METHODS:There were 328 patients assigned to the placebo arm and 317 to the imatinib arm. Median patient follow-up was 74 months. There were 645 tumor specimens available for mitotic rate or mutation analysis. RESULTS:RFS remained superior in the imatinib arm (hazard ratio, 0.6; 95% CI, 0.43 to 0.75; Cox model-adjusted P < .001). On multivariable analysis of patients in the placebo arm, large tumor size, small bowel location, and high mitotic rate were associated with lower RFS, whereas tumor genotype was not significantly associated with RFS. Multivariable analysis of patients in the imatinib arm yielded similar findings. When comparing the two arms, imatinib therapy was associated with higher RFS in patients with a KIT exon 11 deletion of any type, but not a KIT exon 11 insertion or point mutation, KIT exon 9 mutation, PDGFRA mutation, or wild-type tumor, although some of these patient groups were small. Adjuvant imatinib did not seem to alter overall survival. CONCLUSION:Our findings show that tumor size, location, and mitotic rate, but not tumor genotype, are associated with the natural history of GIST. Patients with KIT exon 11 deletions assigned to 1 year of adjuvant imatinib had a longer RFS.

Full Text

Duke Authors

Cited Authors

  • Corless, CL; Ballman, KV; Antonescu, CR; Kolesnikova, V; Maki, RG; Pisters, PWT; Blackstein, ME; Blanke, CD; Demetri, GD; Heinrich, MC; von Mehren, M; Patel, S; McCarter, MD; Owzar, K; DeMatteo, RP

Published Date

  • May 2014

Published In

Volume / Issue

  • 32 / 15

Start / End Page

  • 1563 - 1570

PubMed ID

  • 24638003

Pubmed Central ID

  • 24638003

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

International Standard Serial Number (ISSN)

  • 0732-183X

Digital Object Identifier (DOI)

  • 10.1200/JCO.2013.51.2046

Language

  • eng