Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2014 May 20;32(15):1563-70.
doi: 10.1200/JCO.2013.51.2046. Epub 2014 Mar 17.

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

Christopher L Corless  1 , Karla V Ballman  2 , Cristina R Antonescu  2 , Violetta Kolesnikova  2 , Robert G Maki  2 , Peter W T Pisters  2 , Martin E Blackstein  2 , Charles D Blanke  2 , George D Demetri  2 , Michael C Heinrich  2 , Margaret von Mehren  2 , Shreyaskumar Patel  2 , Martin D McCarter  2 , Kouros Owzar  2 , Ronald P DeMatteo  2
Affiliations
Randomized Controlled Trial

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

Christopher L Corless et al. J Clin Oncol. .

Erratum in

  • J Clin Oncol. 2014 Oct 20;32(30):3462

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00041197.

PubMed Disclaimer

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram.
Fig 2.
Fig 2.
(A) Recurrence-free and (B) overall survival in entire population.
Fig 3.
Fig 3.
Effect of (A) mitotic rate and (B, C) genotype on recurrence-free survival in placebo group. del, deletion; ins, insertion; PM, point mutation; WT, wild type.
Fig 4.
Fig 4.
Relationship between KIT exon 11 mutation and effect of imatinib treatment.
See this image and copyright information in PMC

References

    1. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472–480. - PubMed
    1. Debiec-Rychter M, Sciot R, Le Cesne A, et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer. 2006;42:1093–1103. - PubMed
    1. Heinrich MC, Owzar K, Corless CL, et al. Correlation of kinase genotype and clinical outcome in the North American Intergroup phase III trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol. 2008;26:5360–5367. - PMC - PubMed
    1. Gastrointestinal Stromal Tumor Meta-Analysis (MetaGIST) Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: A meta-analysis of 1,640 patients. J Clin Oncol. 2010;28:1247–1253. - PMC - PubMed
    1. Blanke CD, Rankin C, Demetri GD, et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008;26:626–632. - PubMed

Publication types

MeSH terms

Associated data