To view this page ensure that Adobe Flash Player version 11.1.0 or greater is installed.
Oncology & Hematology Review (US) Highlights
Gastrointestinal Stromal Tumors (GIST)—Paving the Way for Modern
Oncology—Epidemiology, Diagnosis, Treatment
Elena Tsvetkova, MD, FRCPC, 1 E Celia Marginean, MD, FRCPC, FACP, 2 with Carolyn Nessim, MD, MSc, FRCSC 3 and
Shailendra Verma, MD, FRCPC, FACP 4
1. Medical Oncologist, Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada 2. Associate Professor of Pathology,
Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada; 3. Surgical Oncologist and Assistant Professor
of Surgery, University of Ottawa; Clinician Investigator, Ottawa Hospital Research Institute, Ottawa General Hospital, Ontario, Canada; 4. Medical Oncologist, The
Ottawa Hospital Cancer Centre and Associate Professor, Department of Medicine, University of Ottawa, Ontario, Canada
Abstract Gastrointestinal stromal tumors (GIST) are relatively rare tumors arising in the gastrointestinal tract. Clinical presentations of GIST are related
to the site of origin, tumor size, and presence of ulceration. Surgery followed by adjuvant treatment with the BCR-ABL tyrosine kinase inhibitor,
imatinib, for 3 years, in high-risk tumors is the only curative modality. Neoadjuvant treatment with imatinib may be considered in the setting
of locally advanced primary borderline resectable/unresectable disease. Treatment with imatinib in patients with metastatic or unresectable
disease is associated with significant improvements in overall survival (OS) from 18 to 57 months. In patients with metastatic disease, those
responding to imatinib therapy may be considered for surgery and this may be beneficial if resection of the primary and metastatic disease
is feasible and if imatinib is continued post resection. Other locoregional treatments such as radiofrequency ablation (RFA) and hepatic artery
embolization (HAE) with or without chemotherapy may achieve long-lasting disease control and may be considered in highly selected patients.
In patients with primary or secondary resistance to imatinib, second-line treatment with sunitinib and third-line treatment with regorafenib is
recommended. However, despite all of these advances, few patients with metastatic disease are cured and further trials of novel agents or
combinations are required.
Keywords Gastrointestinal stromal tumor, GIST, imatinib, adjuvant, resection, locoregional treatment, metastatic, management, diagnosis,
Disclosure: Elena Tsvetkova, MD, FRCPC, E Celia Marginean, MD, FRCPC, FACP, Carolyn Nessim, MD, MSc, FRCSC, and Shailendra Verma, MD, FRCPC, FACP, have no conflicts
of interest to declare. No funding was received in the publication of this article.
Acknowledgments: All authors have contributed equally to this manuscript.
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation,
and reproduction provided the original author(s) and source are given appropriate credit.
Received: March 31, 2015 Accepted: April 21, 2015 Citation: Oncology & Hematology Review, 2015;11(1):74–86
Correspondence: Shailendra Verma, MD, FRCPC, FACP, Box 500, The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada. E: firstname.lastname@example.org
Gastrointestinal stromal tumors (GIST) are the most common
mesenchymal tumors of the gastrointestinal (GI) tract. Although they
have been recognized as a distinct entity for several decades, it has
only been over the past 10–15 years that these tumors have been
truly studied and further defined by rigorous diagnostic and molecular
criteria. Indeed, one might argue that it was a landmark study involving
the successful treatment of unresectable GIST that launched a new
era of targeted therapy in clinical oncology. In the ensuing years
we have further refined our knowledge of GIST, developed rigorous
diagnostic techniques, surgical interventions and prognostic criteria.
Considerable strides have also been made in adjuvant therapy of
successfully resected localized tumors and in the setting of widespread
disease. In this article, we review the recent progress that has been
made in all of these domains.
Tou ch MEd ica l MEdia
Section 1—Epidemiology—Clinical and
Elena Tsvetkova, E Celia Marginean, and Shailendra Verma
Epidemiology In the past, the diagnosis of GIST has been fraught with difficulty and
they have often been misdiagnosed as leiomyoma, leiomysarcoma,
neurofibroma, or benign/borderline malignant potential tumors.
Consequently, information on the true incidence or prevalence is
scarce and has been largely dependent on retrospective or population-
based studies. The identification of the specific expression of the KIT
protein (CD117) as a reliable phenotypic marker of GIST has led to a re-
appraisal and re-evaluation of pathologic diagnosis and has provided
more concrete information. International epidemiologic data derived
from Sweden and The Netherlands suggests an annual incidence of
14.5 and approximately 12.3 per million, respectively. 1,2 A population-
based study by Tran et al., 3 utilizing the Surveillance, Epidemiology and