Adherence to Guidelines for Adjuvant Imatinib Therapy for GIST: A Multi-institutional Analysis
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.
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.
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.
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.
KeywordsGastrointestinal stromal tumor GIST Surgery Adjuvant Imatinib Tyrosine kinase inhibitor Adherence
- 1.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.Google Scholar
- 2.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.Google Scholar
- 3.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.CrossRefPubMedGoogle Scholar
- 9.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.CrossRefPubMedGoogle Scholar
- 13.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.Google Scholar
- 14.Administration USFaD. FDA Approves Gleevec to Prevent Recurrence of Rare Gastrointestinal Cancer. 2008; http://www.fda.gov/newsevents/newsroom/pressannouncements/2008/ucm116997.htm.
- 17.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.CrossRefGoogle Scholar
- 20.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.CrossRefGoogle Scholar