The Landmark Series: Systemic Therapy for Resectable Gastrointestinal Stromal Tumors
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The Landmark Series: Systemic Therapy for Resectable Gastrointestinal Stromal Tumors Emily Z. Keung, MD1, Chandrajit P. Raut, MD2, and Piotr Rutkowski, MD, PhD3 The University of Texas MD Anderson Cancer Center, Houston, TX; 2Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; 3Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland 1
ABSTRACT Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Complete resection is the only potentially curative treatment, although recurrence is common, occurring in approximately 40–50% of patients. The introduction of effective molecularly targeted therapies for GISTs has dramatically changed the clinical management paradigms for, and prognosis of, patients with intermediate- and high-risk GISTs, as well as those with locally advanced and metastatic disease. In this article, we review landmark studies that evaluated the use and efficacy of the tyrosine kinase inhibitors imatinib and sunitinib in the adjuvant and neoadjuvant settings for resectable primary and limited resectable metastatic GISTs.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, developing most commonly in the stomach and small intestine as a result of activating mutations in KIT or PDGFRA, genes encoding receptor protein tyrosine kinases. Over the past 2 decades, remarkable advances have been made in our understanding of GISTs and the development of molecular-targeted therapies, and tyrosine kinase inhibitors (TKIs) such as imatinib and sunitinib have dramatically changed the management and prognosis of patients with this malignancy. Although surgery is the treatment of choice and the only curative treatment for
Ó The Author(s) 2020 First Received: 26 April 2020 Accepted: 4 July 2020 P. Rutkowski, MD, PhD e-mail: [email protected]
resectable GISTs, recurrence is common, particularly in patients with intermediate- and high-risk GISTs as defined by Miettinen and Lasota.1 On the heels of landmark clinical trials demonstrating remarkable response of imatinib and sunitinib in patients with advanced unresectable and metastatic GIST,2–4 there arose great interest in evaluating the safety and efficacy of using TKI therapy in the adjuvant and neoadjuvant settings for patients with resectable intermediate- and high-risk, locally advanced, or limited resectable metastatic disease. The landmark studies evaluating the use of imatinib for perioperative therapy in resectable GISTs are reviewed below. ADJUVANT THERAPY The success of imatinib in the treatment of advanced unresectable and metastatic GIST2–4 led to great interest in using the drug in the adjuvant setting following primary tumor resection to prevent or delay recurrence and prolong survival. The role of imatinib in the adjuvant setting has been evaluated in several phase II and III clinical trials, as summarized below (Table 1). ACOSOG Z9000
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