Skip to main content
Top
Published in: Journal of Gastrointestinal Surgery 6/2015

01-06-2015 | Original Article

Adherence to Guidelines for Adjuvant Imatinib Therapy for GIST: A Multi-institutional Analysis

Authors: Danielle A. Bischof, Rebecca Dodson, M. Carolina Jimenez, Ramy Behman, Andrei Cocieru, Dan G. Blazer III, Sarah B. Fisher, Malcolm H. Squires III, David A. Kooby, Shishir K. Maithel, Ryan T. Groeschl, T. Clark Gamblin, Todd W. Bauer, Paul J. Karanicolas, Calvin Law, Fayez A. Quereshy, Timothy M. Pawlik

Published in: Journal of Gastrointestinal Surgery | Issue 6/2015

Login to get access

Abstract

Background

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Adjuvant imatinib therapy improves recurrence-free and overall survival following surgery for patients with high-risk GIST; however, the factors associated with use of adjuvant imatinib therapy are unclear, and adherence to adjuvant imatinib has not been investigated. We sought to determine the clinicopathologic predictors of therapy with adjuvant imatinib following surgical resection for GIST and to determine the utilization of adjuvant imatinib in patients who underwent surgical resection of primary GIST in 2009 or later as recommended by National Comprehensive Cancer network (NCCN) guidelines.

Methods

A multi-institutional cohort including 171 patients who underwent surgery for primary GIST at seven high-volume cancer centers in the USA and Canada between January 2009–December 2012 was used in this study. Receipt of adjuvant imatinib therapy was ascertained, and factors associated with imatinib therapy were analyzed.

Results

Following surgery for primary GIST, tumor size (<5.0 cm: ref; 5.0–9.9 cm: odds ratio (OR) 2.36, 95 % confidence interval (CI) 0.74–7.55; >10.0 cm: OR 9.15, 95 % CI 2.28–36.75; p = 0.007), mitotic rate (≤5/50 mitoses per 50 high powered field [HPF]: ref; 6–10/50 HPF: OR 24.91, 95 % CI 3.64–170.35; >10/50 HPF: OR 5.80, 95 % CI 3.64–170.35; p < 0.001), and neoadjuvant therapy (OR 9.52; 95 % CI 2.51–36.14; p = 0.001) were associated with receipt of adjuvant imatinib therapy. Overall, 75 % of patients received appropriate treatment, 23 % of patients were undertreated, and 2 % of patients were overtreated as compared to NCCN guidelines. Adjuvant imatinib therapy was administered in only 53 % of patients for which the NCCN guidelines recommended adjuvant therapy.

Conclusion

The clinicopathologic factors associated with use of adjuvant imatinib therapy in patients following resection of primary GIST are consistent with established risk factors for recurrence. Adjuvant imatinib therapy remains underutilized in patients with intermediate and high-risk GIST and in patients who receive neoadjuvant therapy. Barriers to adjuvant imatinib therapy in this group of patients needs to be further explored.
Literature
1.
go back to reference Miettinen M, Lasota J. Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Archiv : an international journal of pathology. 2001;438(1):1–12. Miettinen M, Lasota J. Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Archiv : an international journal of pathology. 2001;438(1):1–12.
2.
go back to reference Nilsson B, Bumming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era--a population-based study in western Sweden. Cancer. 2005;103(4):821–829. Nilsson B, Bumming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era--a population-based study in western Sweden. Cancer. 2005;103(4):821–829.
3.
go back to reference Tryggvason G, Gislason HG, Magnusson MK, Jonasson JG. Gastrointestinal stromal tumors in Iceland, 1990–2003: the icelandic GIST study, a population-based incidence and pathologic risk stratification study. International journal of cancer. Journal international du cancer. 2005;117(2):289–293.CrossRefPubMed Tryggvason G, Gislason HG, Magnusson MK, Jonasson JG. Gastrointestinal stromal tumors in Iceland, 1990–2003: the icelandic GIST study, a population-based incidence and pathologic risk stratification study. International journal of cancer. Journal international du cancer. 2005;117(2):289–293.CrossRefPubMed
4.
go back to reference Woodall CE, 3rd, Brock GN, Fan J, et al. An evaluation of 2537 gastrointestinal stromal tumors for a proposed clinical staging system. Archives of surgery. 2009;144(7):670–678.CrossRefPubMed Woodall CE, 3rd, Brock GN, Fan J, et al. An evaluation of 2537 gastrointestinal stromal tumors for a proposed clinical staging system. Archives of surgery. 2009;144(7):670–678.CrossRefPubMed
5.
go back to reference Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nature reviews. Cancer. 2011;11(12):865–878.PubMed Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nature reviews. Cancer. 2011;11(12):865–878.PubMed
6.
go back to reference Hohenberger P, Ronellenfitsch U, Oladeji O, et al. Pattern of recurrence in patients with ruptured primary gastrointestinal stromal tumour. The British journal of surgery. 2010;97(12):1854–1859.CrossRefPubMed Hohenberger P, Ronellenfitsch U, Oladeji O, et al. Pattern of recurrence in patients with ruptured primary gastrointestinal stromal tumour. The British journal of surgery. 2010;97(12):1854–1859.CrossRefPubMed
7.
go back to reference Joensuu H, Vehtari A, Riihimaki J, et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. The lancet oncology. 2012;13(3):265–274.CrossRefPubMed Joensuu H, Vehtari A, Riihimaki J, et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. The lancet oncology. 2012;13(3):265–274.CrossRefPubMed
8.
go back to reference Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. The American journal of surgical pathology. 2005;29(1):52–68.CrossRefPubMed Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. The American journal of surgical pathology. 2005;29(1):52–68.CrossRefPubMed
9.
go back to reference Miettinen M, Makhlouf H, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. The American journal of surgical pathology. 2006;30(4):477–489.CrossRefPubMed Miettinen M, Makhlouf H, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. The American journal of surgical pathology. 2006;30(4):477–489.CrossRefPubMed
10.
go back to reference Dematteo RP, Gold JS, Saran L, et al. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer. 2008;112(3):608–615.CrossRefPubMed Dematteo RP, Gold JS, Saran L, et al. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer. 2008;112(3):608–615.CrossRefPubMed
11.
go back to reference Dematteo RP, Ballman KV, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373(9669):1097–1104.CrossRefPubMedCentralPubMed Dematteo RP, Ballman KV, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373(9669):1097–1104.CrossRefPubMedCentralPubMed
12.
go back to reference Joensuu H, Eriksson M, Sundby Hall K, et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA : the journal of the American Medical Association. 2012;307(12):1265–1272.CrossRef Joensuu H, Eriksson M, Sundby Hall K, et al. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA : the journal of the American Medical Association. 2012;307(12):1265–1272.CrossRef
13.
go back to reference von Mehren MG, S.; Meyer, C.; Riedel, R.; Van Tine, B. Soft Tissue Sarcoma. NCCN Clinical Practice Guidelines in Oncology. 2013;Version 1.2013. Accessed 2013. von Mehren MG, S.; Meyer, C.; Riedel, R.; Van Tine, B. Soft Tissue Sarcoma. NCCN Clinical Practice Guidelines in Oncology. 2013;Version 1.2013. Accessed 2013.
15.
go back to reference Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Annals of surgery. 2004;240(2):205–213.CrossRefPubMedCentralPubMed Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Annals of surgery. 2004;240(2):205–213.CrossRefPubMedCentralPubMed
16.
go back to reference Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. The New England journal of medicine. 2002;347(7):472–480.CrossRefPubMed Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. The New England journal of medicine. 2002;347(7):472–480.CrossRefPubMed
17.
go back to reference Heinrich MC, Joensuu H, Demetri GD, et al. Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases. Clinical cancer research : an official journal of the American Association for Cancer Research. 2008;14(9):2717–2725.CrossRef Heinrich MC, Joensuu H, Demetri GD, et al. Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases. Clinical cancer research : an official journal of the American Association for Cancer Research. 2008;14(9):2717–2725.CrossRef
18.
go back to reference Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Human pathology. 2008;39(10):1411–1419.CrossRefPubMed Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Human pathology. 2008;39(10):1411–1419.CrossRefPubMed
19.
go back to reference Merkow RP, Bentrem DJ, Mulcahy MF, et al. Effect of postoperative complications on adjuvant chemotherapy use for stage III colon cancer. Annals of surgery. 2013;258(6):847–853.CrossRefPubMed Merkow RP, Bentrem DJ, Mulcahy MF, et al. Effect of postoperative complications on adjuvant chemotherapy use for stage III colon cancer. Annals of surgery. 2013;258(6):847–853.CrossRefPubMed
20.
go back to reference 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008;26(33):5360–5367.CrossRef 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008;26(33):5360–5367.CrossRef
Metadata
Title
Adherence to Guidelines for Adjuvant Imatinib Therapy for GIST: A Multi-institutional Analysis
Authors
Danielle A. Bischof
Rebecca Dodson
M. Carolina Jimenez
Ramy Behman
Andrei Cocieru
Dan G. Blazer III
Sarah B. Fisher
Malcolm H. Squires III
David A. Kooby
Shishir K. Maithel
Ryan T. Groeschl
T. Clark Gamblin
Todd W. Bauer
Paul J. Karanicolas
Calvin Law
Fayez A. Quereshy
Timothy M. Pawlik
Publication date
01-06-2015
Publisher
Springer US
Published in
Journal of Gastrointestinal Surgery / Issue 6/2015
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-015-2782-7

Other articles of this Issue 6/2015

Journal of Gastrointestinal Surgery 6/2015 Go to the issue