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

Corless, C. L., Ballman, K. V., Antonescu, C. R., Kolesnikova, V., Maki, R. G., Pisters, P. W., Blackstein, M. E., Blanke, C. D., Demetri, G. D., Heinrich, M. C., von Mehren, M., Patel, S., McCarter, M. D., Owzar, K., DeMatteo, R. P. (May 2014) Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor: the ACOSOG Z9001 trial. J Clin Oncol, 32 (15). pp. 1563-70. ISSN 1527-7755 (Electronic)0732-183X (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/24638003
DOI: 10.1200/JCO.2013.51.2046

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.

Item Type: Paper
Uncontrolled Keywords: Adolescent Adult Aged Aged, 80 and over Antineoplastic Agents/administration & dosage Benzamides/*administration & dosage Chemotherapy, Adjuvant Chi-Square Distribution DNA Mutational Analysis Disease-Free Survival Double-Blind Method Exons Female Gastrointestinal Stromal Tumors/genetics/mortality/pathology/*therapy Genetic Predisposition to Disease Humans Imatinib Mesylate Kaplan-Meier Estimate Male Middle Aged Mitotic Index Multivariate Analysis *Mutation Neoplasm Recurrence, Local Patient Selection Phenotype Piperazines/*administration & dosage Precision Medicine Proportional Hazards Models Protein Kinase Inhibitors/administration & dosage Proto-Oncogene Proteins c-kit/*genetics Pyrimidines/*administration & dosage Receptor, Platelet-Derived Growth Factor alpha/*genetics Risk Factors Time Factors Treatment Outcome Tumor Burden Young Adult
Subjects: diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > cancer types > gastrointestinal stromal tumors
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: 20 May 2014
Date Deposited: 20 Oct 2016 15:48
Last Modified: 20 Oct 2016 15:48
PMCID: PMC4026579
Related URLs:
URI: http://repository.cshl.edu/id/eprint/33760

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