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, Karla V. Ballman, Cristina R. Antonescu, Violetta Kolesnikova, Robert G. Maki, Peter W T Pisters, Martin E. Blackstein, Charles D. Blanke, George D. Demetri, Michael C. Heinrich, Margaret Von Mehren, Shreyaskumar Patel, Martin D. McCarter, Kouros Owzar, Ronald P. DeMatteo

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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.

Original languageEnglish (US)
Pages (from-to)1563-1570
Number of pages8
JournalJournal of Clinical Oncology
Volume32
Issue number15
DOIs
StatePublished - May 20 2014

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Survival
Recurrence
Neoplasms
Exons
Therapeutics
Placebos
Genotype
Surgeons
Mutation
Insertional Mutagenesis
Mutation Rate
Imatinib Mesylate
Natural History
Proportional Hazards Models
Point Mutation
Randomized Controlled Trials

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Corless, C. L., Ballman, K. V., Antonescu, C. R., Kolesnikova, V., Maki, R. G., Pisters, P. W. T., ... DeMatteo, R. P. (2014). Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor: The ACOSOG Z9001 trial. Journal of Clinical Oncology, 32(15), 1563-1570. https://doi.org/10.1200/JCO.2013.51.2046

Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor : The ACOSOG Z9001 trial. / Corless, Christopher L.; Ballman, Karla V.; Antonescu, Cristina R.; Kolesnikova, Violetta; Maki, Robert G.; Pisters, Peter W T; Blackstein, Martin E.; Blanke, Charles D.; Demetri, George D.; Heinrich, Michael C.; Von Mehren, Margaret; Patel, Shreyaskumar; McCarter, Martin D.; Owzar, Kouros; DeMatteo, Ronald P.

In: Journal of Clinical Oncology, Vol. 32, No. 15, 20.05.2014, p. 1563-1570.

Research output: Contribution to journalArticle

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 2014, 'Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor: The ACOSOG Z9001 trial', Journal of Clinical Oncology, vol. 32, no. 15, pp. 1563-1570. https://doi.org/10.1200/JCO.2013.51.2046
Corless, Christopher L. ; Ballman, Karla V. ; Antonescu, Cristina R. ; Kolesnikova, Violetta ; Maki, Robert G. ; Pisters, Peter W T ; Blackstein, Martin E. ; Blanke, Charles D. ; Demetri, George D. ; Heinrich, Michael C. ; Von Mehren, Margaret ; Patel, Shreyaskumar ; McCarter, Martin D. ; Owzar, Kouros ; DeMatteo, Ronald P. / Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor : The ACOSOG Z9001 trial. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 15. pp. 1563-1570.
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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.",
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T1 - Pathologic and molecular features correlate with long-term outcome after adjuvant therapy of resected primary GI stromal tumor

T2 - The ACOSOG Z9001 trial

AU - Corless, Christopher L.

AU - Ballman, Karla V.

AU - Antonescu, Cristina R.

AU - Kolesnikova, Violetta

AU - Maki, Robert G.

AU - Pisters, Peter W T

AU - Blackstein, Martin E.

AU - Blanke, Charles D.

AU - Demetri, George D.

AU - Heinrich, Michael C.

AU - Von Mehren, Margaret

AU - Patel, Shreyaskumar

AU - McCarter, Martin D.

AU - Owzar, Kouros

AU - DeMatteo, Ronald P.

PY - 2014/5/20

Y1 - 2014/5/20

N2 - 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.

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