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Beecroft JR, Brar S, Feng X, Hamilton T, Han-Lee C, Henning JW, Josephy PD, Khalili K, Ko YJ, Lemieux C, Liu DM, MacDonald DB, Noujaim J, Pollett A, Salawu A, Saleh R, Smrke A, Warren BE, Zbuk K, Razak AA. Pan-Canadian consensus recommendations for GIST management in high- and low-throughput centres across Canada. Ther Adv Med Oncol 2024; 16:17588359241266179. [PMID: 39386314 PMCID: PMC11461906 DOI: 10.1177/17588359241266179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 06/18/2024] [Indexed: 10/12/2024] Open
Abstract
Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.
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Affiliation(s)
- J. Robert Beecroft
- Division of Interventional Radiology, Joint Department of Medical Imaging, University Health Network, Mount Sinai Hospital, Toronto, ON, Canada
| | - Savtaj Brar
- Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Xiaolan Feng
- Division of Medical Oncology, Tom Baker Cancer Center, Calgary, AB, Canada
| | - Trevor Hamilton
- Department of Surgery, BC Cancer, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Cheng Han-Lee
- Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, AB, Canada
| | - Jan-Willem Henning
- Department of Oncology, Tom Baker Cancer Centre, Cuming School of Medicine, University of Calgary, Calgary, AB, Canada
| | | | - Korosh Khalili
- Department of Medical Imaging, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Yoo-Joung Ko
- Department of Medicine, St. Michael’s Hospital, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Christopher Lemieux
- Division of Hematology and Medical Oncology, Centre Hospitalier Universitaire de Québec, Université Laval, Quebec City, QC, Canada
| | - David M. Liu
- Department of Radiology, University of British Columbia, School of Biomedical Engineering, Vancouver, BC, Canada
- Department of Interventional Radiology, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - D. Blair MacDonald
- Department of Medical Radiology, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
| | - Jonathan Noujaim
- Division of Medical Oncology, Hôpital Maisonneuve-Rosemont, University of Montreal, Montreal, QC, Canada
| | - Aaron Pollett
- Pathology and Laboratory Medicine, Division of Diagnostic Medical Genetics, Mount Sinai Hospital, Toronto, ON, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Abdulazeez Salawu
- Division of Medical Oncology, Princess Margaret Cancer Centre, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Ramy Saleh
- Division of Medical Oncology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Alannah Smrke
- Division of Medical Oncology, BC Cancer, University of British Columbia, Vancouver, BC, Canada
| | - Blair E. Warren
- Department of Medical Imaging, University of Toronto, Toronto, ON, Canada
| | - Kevin Zbuk
- Department of Oncology, McMaster University, Hamilton, ON, Canada
| | - Albiruni Abdul Razak
- Division of Medical Oncology, Princess Margaret Cancer Centre, Mount Sinai Hospital, University of Toronto, 610 University Ave., Toronto, ON M2G 2M9, Canada
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Hirota S, Tateishi U, Nakamoto Y, Yamamoto H, Sakurai S, Kikuchi H, Kanda T, Kurokawa Y, Cho H, Nishida T, Sawaki A, Ozaka M, Komatsu Y, Naito Y, Honma Y, Takahashi F, Hashimoto H, Udo M, Araki M, Nishidate S. English version of Japanese Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) issued by the Japan Society of Clinical Oncology. Int J Clin Oncol 2024; 29:647-680. [PMID: 38609732 PMCID: PMC11130037 DOI: 10.1007/s10147-024-02488-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 02/12/2024] [Indexed: 04/14/2024]
Abstract
The Japan Society of Clinical Oncology Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) have been published in accordance with the Minds Manual for Guideline Development 2014 and 2017. A specialized team independent of the working group for the revision performed a systematic review. Since GIST is a rare type of tumor, clinical evidence is not sufficient to answer several clinical and background questions. Thus, in these guidelines, we considered that consensus among the experts who manage GIST, the balance between benefits and harms, patients' wishes, medical economic perspective, etc. are important considerations in addition to the evidence. Although guidelines for the treatment of GIST have also been published by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), there are some differences between the treatments proposed in those guidelines and the treatments in the present guidelines because of the differences in health insurance systems among countries.
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Affiliation(s)
- Seiichi Hirota
- Department of Surgical Pathology, Hyogo Medical University School of Medicine, Nishinomiya, Japan.
| | - Ukihide Tateishi
- Department of Diagnostic Radiology and Nuclear Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yuji Nakamoto
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hidetaka Yamamoto
- Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Shinji Sakurai
- Department of Diagnostic Pathology, Japan Community Healthcare Organization Gunma Central Hospital, Maebashi, Japan
| | - Hirotoshi Kikuchi
- Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology, Southern TOHOKU General Hospital, Koriyama, Japan
| | - Yukinori Kurokawa
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Haruhiko Cho
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Toshirou Nishida
- Department of Surgery, Japan Community Healthcare Organization Osaka Hospital, Osaka, Japan
| | - Akira Sawaki
- Department of Medical Oncology, Shonan Kamakura General Hospital, Kamakura, Japan
| | - Masato Ozaka
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yoshito Komatsu
- Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo, Japan
| | - Yoichi Naito
- Department of General Internal Medicine, National Cancer Center Hospital East, Kashiwa, Japan
| | - Yoshitaka Honma
- Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Fumiaki Takahashi
- Department of Information Science, Iwate Medical University, Morioka, Japan
| | | | - Midori Udo
- Nursing Department, Osaka Police Hospital, Osaka, Japan
| | - Minako Araki
- Association of Chubu GIST Patients and Their Families, Nagoya, Japan
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Naito Y, Nishida T, Doi T. Current status of and future prospects for the treatment of unresectable or metastatic gastrointestinal stromal tumours. Gastric Cancer 2023; 26:339-351. [PMID: 36913072 PMCID: PMC10115693 DOI: 10.1007/s10120-023-01381-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 03/02/2023] [Indexed: 03/14/2023]
Abstract
Gastrointestinal stromal tumours (GISTs) are soft-tissue sarcomas of the gastrointestinal tract. Surgery is the standard treatment for localised disease, but the risk of relapse and progression to more advanced disease is substantial. Following the discovery of the molecular mechanisms underlying GISTs, targeted therapies for advanced GIST were developed, with the first being the tyrosine kinase inhibitor (TKI) imatinib. Imatinib is recommended in international guidelines as first-line therapy to reduce the risk of GIST relapse in high-risk patients, and for locally advanced, inoperable and metastatic disease. Unfortunately, imatinib resistance frequently occurs and, therefore, second-line (sunitinib) and third-line (regorafenib) TKIs have been developed. Treatment options are limited for patients with GIST that has progressed despite these therapies. A number of other TKIs for advanced/metastatic GIST have been approved in some countries. Ripretinib is approved as fourth-line treatment of GIST and avapritinib is approved for GIST harbouring specific genetic mutations, while larotrectinib and entrectinib are approved for solid tumours (including GIST) with specific genetic mutations. In Japan, pimitespib, a heat shock protein 90 (HSP90) inhibitor, is now available as a fourth-line therapy for GIST. Clinical studies of pimitespib have indicated that it has good efficacy and tolerability, importantly not displaying the ocular toxicity of previously developed HSP90 inhibitors. Additional approaches for advanced GIST have been investigated, including alternative uses of currently available TKIs (such as combination therapy), novel TKIs, antibody-drug conjugates, and immunotherapies. Given the poor prognosis of advanced GIST, the development of new therapies remains an important goal.
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Affiliation(s)
- Yoichi Naito
- Department of General Internal Medicine, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
- Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan.
- Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
| | - Toshirou Nishida
- Department of Surgery, Japan Community Health Care Organization Osaka Hospital, Osaka, Japan
- National Cancer Center Hospital, Tsukiji, Tokyo, Japan
| | - Toshihiko Doi
- Department of Experimental Therapeutics, National Cancer Center Hospital East, Kashiwa, Japan
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Lian J, Feng M, Zhang S, Lu H. Case report: 10-year survival of a patient with a primary hepatic gastrointestinal stromal tumor. Front Oncol 2022; 12:1035824. [PMID: 36530972 PMCID: PMC9752909 DOI: 10.3389/fonc.2022.1035824] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Accepted: 11/14/2022] [Indexed: 07/19/2024] Open
Abstract
BACKGROUND Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract. Extra-gastrointestinal stromal tumors (EGISTs) predominantly arise outside the gastrointestinal tract, although primary hepatic GISTs are extremely rare. GISTs are highly aggressive; they often grow to a large size. Here, we report the 10-year survival of a patient with a primary hepatic GIST following sequential response therapy. CASE PRESENTATION A 50-year-old Chinese man complained of fatigue and slight abdominal pain, and presented with a large lump in the liver, which was detected by computed tomography (CT). He was subsequently diagnosed with a primary hepatic GIST, based on CT-guided fine needle aspiration cytology and immunohistochemistry analyses. The presence of GIST or EGIST metastases was excluded using CT, esophagogastroduodenoscopy, colonoscopy, and ultrasound. Cytological examination showed that the tumor was composed of epithelioid and spindle cells. Immunohistochemistry analysis revealed positive staining for CD117 (KIT) and DOG1, and negative staining for CD34, S-100, and α-smooth muscle actin (SMA). Following tumor ablation with argon-helium cryosurgery, the patient received imatinib mesylate for 61 months. However, this treatment was discontinued because of disease progression, at which point interventional therapy was administered once. One month later, sunitinib malate was administered for 71 months. The patient achieved long-term survival for 135 months. CONCLUSIONS EGISTs can be easily misdiagnosed as other types of tumors because they have no specific characteristics to distinguish them during imaging examinations. However, our case study demonstrates that the long-term survival of patients with EGISTs can be achieved with molecular targeted therapy.
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Affiliation(s)
- Jie Lian
- Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Meiyan Feng
- Department of Tumor Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
| | - Shumei Zhang
- College of Information and Computer Engineering, Northeast Forestry University, Harbin, China
| | - Haibo Lu
- Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China
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Patterson T, Li H, Chai J, Debruyns A, Simmons C, Hart J, Pollock P, Holloway CL, Truong PT, Feng X. Locoregional Treatments for Metastatic Gastrointestinal Stromal Tumor in British Columbia: A Retrospective Cohort Study from January 2008 to December 2017. Cancers (Basel) 2022; 14:cancers14061477. [PMID: 35326632 PMCID: PMC8945875 DOI: 10.3390/cancers14061477] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 03/07/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary It is not known if surgery, radiation treatment (RT) or other types of locolregional treatment (LRT) may be beneficial for patients with metastatic gastrointestinal stromal tumor (mGIST) in addition to systemic treatment. Our study aims to address this question by analyzing a cohort of 127 mGIST patients in British Columbia over a decade (from January 2008 to December 2017). We showed that mGIST patients who underwent surgery and LRT seemed to have better survival when compared to patients who did not undergo surgery and LRT. However, this treatment strategy should only be considered in patients with limited volume metastatic disease or oligoprogression while the rest of the disease is well controlled with systemic treatment. In addition, RT can offer palliative benefits such as pain relief and bleeding control. Our study, consistent with other retrospective studies, supports LRT consideration in selected mGIST patients within a multidisciplinary setting. This approach is not considered as a “standard of care” due to lack of prospective clinical trials but may improve clinical outcome for some mGIST patients. Abstract Introduction: The role of surgery and non-surgical locoregional treatments (LRT) such as radiation therapy (RT) and local ablation techniques in patients with metastatic gastrointestinal stromal tumor (GIST) is unclear. This study examines LRT practice patterns in metastatic GIST and their clinical outcomes in British Columbia (BC). Methods: Patients diagnosed with either recurrent or de novo metastatic GIST from January 2008 to December 2017 were identified. Clinical characteristics and outcomes were analyzed in patients who underwent LRT, including surgical resection of the primary tumor or metastectomy, RT, or other local ablative procedures. Results: 127 patients were identified: 52 (41%) had de novo metastasis and 75 (59%) had recurrent metastasis. Median age was 67 (23–90 years), 58.2% were male, primary site was 33.1% stomach, 40.2% small intestine, 11% rectum/pelvis, and 15.7% others. 37 (29.1%) of patients received palliative surgery, the majority of which had either primary tumor removal only (43.3%) or both primary tumor removal and metastectomy (35.1%). A minority of patients underwent metastectomy only (21.6%). A total of 12 (9.5%) patients received palliative RT to metastatic sites only (58.3%) or primary tumors only (41.7%), mostly for symptomatic control (n = 9). A few patients (n = 3) received local ablation for liver metastatic deposits with 1 patient receiving microwave ablation (MWA) and 2 receiving radiofrequency ablation (RFA). Most patients (n = 120, 94.5%) received some type of systemic treatment. It is notable that prolonged progression free survival (PFS) was observed for the majority of patients who underwent surgery in the metastatic setting with a median PFS of 20.5 (95% confidence interval (CI): 14.29–40.74) months. In addition, significantly higher median overall survival (mOS) was observed in patients who underwent surgery (97.15 months; 95% CI: 77.7-not reached) and LRT (78.98 months; 95% CI: 65.58-not reached) versus no surgery (45.37 months; 95% CI: 38.7–64.69) and no LRT (45.27 months; 95% CI: 33.25–58.66). Almost all patients (8 out of 9) achieved symptomatic improvement after palliative RT. All 3 patients achieved partial response and 2 out of 3 patients had relatively durable responses of 1 year or more after local ablation. Discussion: This study is among the first to systematically examine the use of various LRT in metastatic GIST management. Integration of LRT with systemic treatments may potentially provide promising durable response and prolonged survival for highly selected metastatic GIST patients with low volume disease, limited progression and otherwise well controlled on systemic treatments. These observations, consistent with others, add to the growing evidence that supports the judicious use of LRT in combination with systemic treatments to further optimize the care of metastatic GIST patients.
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Affiliation(s)
- Tiffany Patterson
- Clinical Trials, BC Cancer—Vancouver Island Center, Victoria, BC V8R 6V5, Canada; (T.P.); (P.P.)
| | - Haocheng Li
- Department of Mathematics and Statistics, University of Calgary, Calgary, AB T2N 1N4, Canada;
| | - Jocelyn Chai
- Department of Medicine, University of British Columbia, Vancouver, BC V1Y 1T3, Canada;
| | - Angeline Debruyns
- Department of Medicine, Island Medical Program, University of British Columbia, Victoria, BC V1Y 1T3, Canada;
| | - Christine Simmons
- Department of Medical Oncology, University of British Columbia, BC Cancer—Vancouver Center, Vancouver, BC V1Y 1T3, Canada;
| | - Jason Hart
- Department of Medical Oncology, University of British Columbia, BC Cancer—Vancouver Island Center, Victoria, BC V1Y 1T3, Canada;
| | - Phil Pollock
- Clinical Trials, BC Cancer—Vancouver Island Center, Victoria, BC V8R 6V5, Canada; (T.P.); (P.P.)
| | - Caroline L. Holloway
- Department of Radiation Oncology, University of British Columbia, BC Cancer—Vancouver Island Center, Victoria, BC V1Y 1T3, Canada; (C.L.H.); (P.T.T.)
| | - Pauline T. Truong
- Department of Radiation Oncology, University of British Columbia, BC Cancer—Vancouver Island Center, Victoria, BC V1Y 1T3, Canada; (C.L.H.); (P.T.T.)
| | - Xiaolan Feng
- Department of Medicine, University of British Columbia, Vancouver, BC V1Y 1T3, Canada;
- Department of Medical Oncology, Tom Baker Cancer Center, Calgary, AB T2N 4N2, Canada
- Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
- Correspondence:
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Abstract
OBJECTIVE The outcome for patients with unresectable hepatic sarcoma is poor with a median survival period of 12-16 months. The purpose of this study was to evaluate liver-directed transcatheter therapies for the treatment of hepatic sarcomas. MATERIALS AND METHODS In a retrospective study, the cases of patients with primary and metastatic hepatic sarcoma treated by transcatheter embolization, chemoembolization, and 90Y radioembolization between 2004 and 2015 were identified. Response Evaluation Criteria in Solid Tumors version 1.1 response was assessed for the target tumor. Survival was assessed by means of Kaplan-Meier analysis. RESULTS Twenty-eight patients (17 [61%] men, 11 [39%] women; median age, 47 years) were included. Eighteen patients were treated electively. Two of the electively treated patients underwent embolization; eight, chemoembolization; six, radioembolization; and two, a combination of transcatheter treatments. Treatment was well tolerated; only one patient had grade 3 hepatic toxicity. The objective response rate of the index tumor was 61%, and the median overall survival period was 26.7 months. Ten patients underwent emergency embolization to control acute hemorrhage from tumor rupture. The median overall survival periods were 611 days for the patients with ruptured gastrointestinal stromal tumors (GIST) (n = 3) and 19 days for the patients with ruptured angiosarcoma (n = 7). CONCLUSION Liver-directed transcatheter therapies are safe and may have a role in the elective management of unresectable primary and metastatic liver sarcomas. Emergency embolization for ruptured GIST may be effective for stabilizing the patient's condition and allowing more definitive therapy in the future. However, emergency embolization has limited efficacy in treating patients with ruptured angiosarcoma, likely because of substantial venous bleeding at rupture and the aggressive behavior of this lesion.
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Gaba RC, Lokken RP, Hickey RM, Lipnik AJ, Lewandowski RJ, Salem R, Brown DB, Walker TG, Silberzweig JE, Baerlocher MO, Echenique AM, Midia M, Mitchell JW, Padia SA, Ganguli S, Ward TJ, Weinstein JL, Nikolic B, Dariushnia SR. Quality Improvement Guidelines for Transarterial Chemoembolization and Embolization of Hepatic Malignancy. J Vasc Interv Radiol 2017; 28:1210-1223.e3. [PMID: 28669744 DOI: 10.1016/j.jvir.2017.04.025] [Citation(s) in RCA: 86] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Accepted: 04/29/2017] [Indexed: 02/07/2023] Open
Affiliation(s)
- Ron C Gaba
- Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612.
| | - R Peter Lokken
- Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612
| | - Ryan M Hickey
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Andrew J Lipnik
- Division of Interventional Radiology, Department of Radiology, University of Illinois Hospital & Health Sciences System, 1740 West Taylor Street, MC 931, Chicago, IL 60612
| | - Robert J Lewandowski
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Riad Salem
- Section of Vascular and Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Daniel B Brown
- Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - T Gregory Walker
- Division of Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | | | | | - Ana Maria Echenique
- Department of Interventional Radiology, University of Miami School of Medicine, Coral Gables, Florida
| | - Mehran Midia
- Interventional Radiology, McMaster University, Hamilton, Ontario, Canada
| | - Jason W Mitchell
- Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, Atlanta, Georgia
| | - Siddharth A Padia
- Division of Interventional Radiology, Department of Radiology, David Geffen School of Medicine at University of California, Los Angeles, California
| | - Suvranu Ganguli
- Division of Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Center for Image Guided Cancer Therapy, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Thomas J Ward
- Vascular and Interventional Radiology, Florida Hospital, Orlando, Florida
| | - Jeffrey L Weinstein
- Vascular and Interventional Radiology, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Boris Nikolic
- Department of Radiology, Stratton Medical Center, Albany, New York
| | - Sean R Dariushnia
- Interventional Radiology and Image Guided Medicine, Emory University School of Medicine, Atlanta, Georgia
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Cheng X, Chen D, Chen W, Sheng Q. Primary gastrointestinal stromal tumor of the liver: A case report and review of the literature. Oncol Lett 2016; 12:2772-2776. [PMID: 27698856 DOI: 10.3892/ol.2016.4981] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Accepted: 03/18/2016] [Indexed: 12/17/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. A small portion of GISTs are observed in extra-gastrointestinal regions, primarily in the omentum, mesentery and retroperioneum, and these types of GISTs are referred to as extra-gastrointestinal stromal tumors. The present study reports of a patient with unique primary liver GIST. The patient underwent en bloc resection and post-operative administration of imatinib, and subsequently experienced a good prognosis. The present case is followed by a brief review of reported cases of liver GISTs identified in the literature. The literature revealed that primary liver GISTs are usually large in size and possess a high mitotic index, which contributes to malignant characterization, thus classifying these tumors as high-risk. En bloc resection remains the mainstay of treatment for resectable primary liver GISTs. However, the prognosis of these patients is not favorable. Perioperative administration of imatinib may be useful to a certain extent, and interventional therapy, including radiofrequency ablation, should be considered.
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Affiliation(s)
- Xiaobin Cheng
- Department of Colorectal Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Dong Chen
- Department of Colorectal Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Wenbin Chen
- Department of Colorectal Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Qinsong Sheng
- Department of Colorectal Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
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Ang C, Maki RG. Contemporary Management of Metastatic Gastrointestinal Stromal Tumors: Systemic and Locoregional Approaches. Oncol Ther 2016; 4:1-16. [PMID: 28261637 PMCID: PMC5315077 DOI: 10.1007/s40487-015-0014-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Indexed: 12/25/2022] Open
Abstract
The treatment of metastatic gastrointestinal stromal tumors (GISTs) changed dramatically with the introduction of imatinib into the therapeutic lexicon in 2001. Over the past 15 years, tyrosine kinase inhibitors in the adjuvant and metastatic settings have remained the standard of care for this disease, though alternate classes of agents and new therapeutic targets are being actively explored in clinical trials. Although data are limited, the use of surgical and non-surgical locoregional techniques for the treatment of GIST metastases has increased and given reports of promising and durable responses. Herein we provide an overview of the contemporary therapeutic landscape of metastatic GIST.
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Affiliation(s)
- Celina Ang
- Division of Hematology/Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA
| | - Robert G Maki
- Division of Hematology/Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA
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10
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Chen H, Gao S, Yang XZ, Chen LJ, Liu P, Xu HF. Comparison of Safety and Efficacy of Different Models of Target Vessel Regional Chemotherapy for Gastric Cancer with Liver Metastases. Chemotherapy 2015; 61:99-107. [PMID: 26618449 DOI: 10.1159/000440945] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Accepted: 09/07/2015] [Indexed: 11/19/2022]
Abstract
BACKGROUND/AIMS We previously demonstrated the safety and efficacy of low-dose, short-interval target vessel regional chemotherapy (TVRC(LDSI)) delivered through the hepatic artery with transarterial embolization (TAE) in patients with advanced gastric cancer (AGC). The present study aimed to compare the efficacy of TAE + TVRC(LDSI) with that of standard TAE + TVRC in AGC patients with liver metastases who failed to respond to first- or second-line systemic chemotherapy. METHODS This study recruited a total of 58 GC patients with liver metastases after failure of first- or second-line systemic chemotherapy. Twenty-eight patients were assigned to the TAE + TVRC(LDSI) group and 30 patients to the TAE + TVRC group. The primary end point was overall survival (OS(TVRC)), which was defined as the time from the initiation of TVRC until the last follow-up or death. RESULTS OS(TVRC), time to progression (TTP) until appearance of intra- and extrahepatic metastases, and overall TTP and treatment periods in the TAE + TVRC(LDSI) group were all significantly longer than in the TAE + TVRC group (all p < 0.001). CONCLUSION TAE + TVRC(LDSI) had a higher efficacy and safety, which was reflected by OS rates, progression-free survival rates, longer duration of treatment and milder side effects compared to standard TAE + TVRC.
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Takaki H, Litchman T, Covey A, Cornelis F, Maybody M, Getrajdman GI, Sofocleous CT, Brown KT, Solomon SB, Alago W, Erinjeri JP. Hepatic artery embolization for liver metastasis of gastrointestinal stromal tumor following imatinib and sunitinib therapy. J Gastrointest Cancer 2015; 45:494-9. [PMID: 25358551 DOI: 10.1007/s12029-014-9663-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE The purpose of the study is to determine the efficacy of hepatic artery embolization (HAE) as a therapy for gastrointestinal stromal tumor (GIST) in patients who are refractory to imatinib and sunitinib. METHODS After institutional review board approval, a retrospective review revealed 11 patients with GIST metastatic to the liver who underwent 15 HAEs between February 2002 and May 2013. These patients were stratified into two groups according to the previous treatment: (a) those treated with HAE as second-line treatment after failing first-line imatinib (n = 3) and (b) those treated with HAE as third-line therapy after failing first-line imatinib and second-line sunitinib (n = 8). Initial therapeutic response, overall survival (OS), progression-free survival (PFS), and safety were evaluated. RESULTS Initial therapeutic response rates at 3 months after HAE were 27.3 % (95 % confidence interval (CI), 6.0-61.0 %) by Response Evaluation Criteria in Solid Tumor (RECIST) version 1.0 and 45.5 % (95 % CI, 16.7-76.6 %) by modified RECIST (mRECIST). The median OS and PFS after HAE were 14.9 and 3.9 months in group A and 23.8 and 3.4 months in group B, respectively. No procedure-related mortality or major complication was observed. CONCLUSIONS HAE is an effective and well-tolerated therapeutic option for GIST liver metastases. Although larger studies are necessary, HAE should be considered as an alternative or adjuvant to third-line or even second-line systemic treatment.
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Affiliation(s)
- Haruyuki Takaki
- Interventional Radiology Service, Memorial Sloan-Kettering Cancer Center, Howard-118, 1275 York Avenue, New York, NY, USA,
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Koo HJ, Shin JH, Shin S, Yoon HK, Ko GY, Gwon DI. Efficacy and Clinical Outcomes of Transcatheter Arterial Embolization for Gastrointestinal Bleeding from Gastrointestinal Stromal Tumor. J Vasc Interv Radiol 2015; 26:1297-304.e1. [PMID: 26190186 DOI: 10.1016/j.jvir.2015.06.005] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 05/29/2015] [Accepted: 06/01/2015] [Indexed: 12/19/2022] Open
Abstract
PURPOSE To evaluate the efficacy and clinical outcomes of transcatheter arterial embolization (TAE) for gastrointestinal (GI) bleeding from gastrointestinal stromal tumor (GIST). MATERIALS AND METHODS TAE was performed in 20 referred patients (male:female = 13:7; median age, 56.3 y) for GI bleeding from GISTs. The locations of GISTs were assessed using contrast-enhanced computed tomography (CT) and catheter angiography. The technical and clinical success of TAE and clinical outcomes including procedure-related complications, recurrent bleeding, 30-day and overall mortality, and cumulative survival were evaluated. RESULTS The sites of GIST-related bleeding or tumor staining were the jejunum (n = 9), stomach (n = 5), ileum (n = 3), duodenum (n = 2), and jejunum and colon (n = 1). Angiography showed bleeding from GIST in 5 patients, and tumor staining was noted in only 15 patients. TAE was performed for patients with and without contrast medium extravasation on angiography. Technical and clinical success rates of TAE were 95% (19 of 20 patients) and 90% (18 of 20 patients), respectively. Recurrent bleeding was noted in 1 patient. There were no procedure-related complications. In 15 patients, surgical resection of the tumors was performed after TAE. The 30-day and overall mortality rates were 10% (2 of 20 patients) and 30% (6 of 20 patients), respectively. CONCLUSIONS TAE is a safe and effective method for controlling GI bleeding from the GIST.
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Affiliation(s)
- Hyun Jung Koo
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Olymphic-ro 43 gil 88, Songpa-Gu, Seoul 138-736, Korea
| | - Ji Hoon Shin
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Olymphic-ro 43 gil 88, Songpa-Gu, Seoul 138-736, Korea.
| | - Sooyoung Shin
- Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Hyun-Ki Yoon
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Olymphic-ro 43 gil 88, Songpa-Gu, Seoul 138-736, Korea
| | - Gi-Young Ko
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Olymphic-ro 43 gil 88, Songpa-Gu, Seoul 138-736, Korea
| | - Dong Il Gwon
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Olymphic-ro 43 gil 88, Songpa-Gu, Seoul 138-736, Korea
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Cao G, Zhu X, Li J, Shen L, Yang R, Chen H, Wang X, Gao S, Xu H, Zhu L, Liu P, Guo J. A comparative study between Embosphere(®) and conventional transcatheter arterial chemoembolization for treatment of unresectable liver metastasis from GIST. Chin J Cancer Res 2014; 26:124-31. [PMID: 24653635 DOI: 10.3978/j.issn.1000-9604.2014.02.11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2013] [Accepted: 02/10/2014] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE Transcatheter arterial chemoembolization (TACE) is a standard treatment for hepatocellular carcinoma (HCC) and/or some unresectable liver metastasis tumors. Hypervascular liver metastatic lesions such as metastasis from gastrointestinal stromal tumor (GIST) are an indication for transcatheter arterial embolization (TAE). The purpose of this study was to evaluate the efficacy and safety of Embosphere(®)-TAE (Embo-TAE) in comparison with conventional TACE (cTACE) for the treatment of liver metastasis from GIST. METHODS A total of 45 patients who underwent TACE between Aug 2008 and Feb 2013 were enrolled. Patients with GIST who underwent TAE with Embosphere(®) (n=19) were compared with controls who received cTACE (n=26). The primary end points were treatment response and treatment-related adverse events. The secondary end points were progression-free survival (PFS) and overall survival (OS). RESULTS The treatment response of Embo-TAE group was significantly higher than that of the cTACE group (P<0.001). The PFS was significantly better in the Embosphere(®)-group than in the cTACE group (56.6 and 42.1 weeks, respectively; P=0.003). However, there was no statistically significant difference in liver toxicity between the two groups (P>0.05). The median OS in the Embo-TAE group was longer than that in the cTACE group (74.0 weeks, 95% CI: 68.2-79.8 vs. 61.7 weeks, 95% CI: 56.2-67.2 weeks) (unadjusted P=0.045). The use of Embo-TAE significantly reduced the risk of death in patients with GIST with liver metastases according to the Cox proportional hazards regression model [hazard ratio (HR): 0.149; 95% CI: 0.064-0.475]. CONCLUSIONS TAE with Embosphere(®) showed better treatment response and delayed tumor progression compared with cTACE. There was no significant difference in treatment-related hepatic toxicities. Embo-TAE thus appears to be a feasible and promising approach in the treatment of liver metastasis from GIST.
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Affiliation(s)
- Guang Cao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 1 Department of Interventional Therapy, 2 Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Xu Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 1 Department of Interventional Therapy, 2 Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jian Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 1 Department of Interventional Therapy, 2 Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Lin Shen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 1 Department of Interventional Therapy, 2 Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Renjie Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 1 Department of Interventional Therapy, 2 Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Hui Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 1 Department of Interventional Therapy, 2 Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Xiaodong Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 1 Department of Interventional Therapy, 2 Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Song Gao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 1 Department of Interventional Therapy, 2 Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Haifeng Xu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 1 Department of Interventional Therapy, 2 Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Linzhong Zhu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 1 Department of Interventional Therapy, 2 Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Peng Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 1 Department of Interventional Therapy, 2 Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jianhai Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), 1 Department of Interventional Therapy, 2 Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
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Cuaron JJ, Goodman KA, Lee N, Wu AJ. External beam radiation therapy for locally advanced and metastatic gastrointestinal stromal tumors. Radiat Oncol 2013; 8:274. [PMID: 24267287 PMCID: PMC4222030 DOI: 10.1186/1748-717x-8-274] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Accepted: 11/20/2013] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The role of radiation therapy (RT) in the management of gastrointestinal stromal tumors (GIST) is not well described. Here we report our institutional experience for patients with locally advanced or metastatic GIST treated with RT. METHODS Between 1997 and 2012, 15 patients with 22 GISTs were treated with RT at our center. The median age was 68 (range, 41-86). Fourteen patients had stage IV disease and 1 patient had stage IIIB disease, per the American Joint Committee on Cancer (AJCC), 7th Edition staging. Tumors were in a variety of locations, and were most commonly referred for palliative treatment. Eighteen of 22 tumors were symptomatic. Prior to RT, 14 of 15 patients received systemic therapy in the form of tyrosine kinase inhibitors (TKIs) (n = 11), chemotherapy (n = 4), or both (n = 1). TKIs were used concurrently for nine tumors (40.9%). No tumors were treated with concurrent chemotherapy. Several fractionation schemes were used, most commonly 3 Gy × 10 (n = 8). Local progression-free survival and overall survival were estimated using the Kaplan-Meier method. Acute toxicity was graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.0. RESULTS The median follow-up was 5.1 months (range, 1.3-28.3). At the time of analysis, 12 patients have died (80%). The estimated 6-month local progression-free survival and overall survival were 57.0% and 57.8%, respectively. Among the 18 symptomatic tumors, at least partial palliation was achieved in 17 (94.4%), and symptoms were completely palliated in eight (44.4%). Treatment was well tolerated, with no Grade 4 or 5 toxicities. There was no Grade ≥3 toxicity associated with concurrent TKI use. CONCLUSIONS In this largest series to date of GISTs treated with RT, a high rate of palliation was achieved for symptomatic tumors in a cohort of advanced stage, heavily pretreated patients. Treatment was well tolerated, and concurrent use of tyrosine kinase inhibitor therapy was not associated with additional toxicity. While follow-up was short, durable control is possible for some patients, providing evidence that GIST is not universally radioresistant and that RT can provide an important benefit in patients with progressive or metastatic disease.
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Affiliation(s)
- John J Cuaron
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
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Abstract
Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms that arise in the gastrointestinal tract, usually in the stomach or the small intestine and rarely elsewhere in the abdomen. They can occur at any age, the median age being 60-65 years, and typically cause bleeding, anaemia, and pain. GISTs have variable malignant potential, ranging from small lesions with a benign behaviour to fatal sarcomas. Most tumours stain positively for the mast/stem cell growth factor receptor KIT and anoctamin 1 and harbour a kinase-activating mutation in either KIT or PDGFRA. Tumours without such mutations could have alterations in genes of the succinate dehydrogenase complex or in BRAF, or rarely RAS family genes. About 60% of patients are cured by surgery. Adjuvant treatment with imatinib is recommended for patients with a substantial risk of recurrence, if the tumour has an imatinib-sensitive mutation. Tyrosine kinase inhibitors substantially improve survival in advanced disease, but secondary drug resistance is common.
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Affiliation(s)
- Heikki Joensuu
- Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
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de la Fuente SG, Deneve JL, Parsons CM, Zager JS, Conley AP, Gonzalez RJ. A comparison between patients with gastrointestinal stromal tumours diagnosed with isolated liver metastases and liver metastases plus sarcomatosis. HPB (Oxford) 2013; 15:655-60. [PMID: 23458233 PMCID: PMC3948531 DOI: 10.1111/hpb.12011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2012] [Accepted: 10/17/2012] [Indexed: 12/12/2022]
Abstract
OBJECTIVES This study was conducted to compare overall survival (OS) in patients presenting with isolated hepatic metastases with that of patients with synchronous metastatic disease to the liver and sarcomatosis on a background of gastrointestinal stromal tumours (GISTs). METHODS Patients presenting with metastatic GISTs during 1999-2009 were identified. Survival outcomes were compared between groups. RESULTS Of the 193 patients with GISTs, 43 patients presented with isolated hepatic metastases and 16 presented with synchronous metastases to the liver and sarcomatosis. Thirteen patients with metastases to the liver and sarcomatosis underwent surgery, and 34 patients with metastatic disease solely to the liver underwent hepatic resection. The proportion of patients treated with preoperative tyrosine kinase inhibitor (TKI) therapy was similar in both groups. Similar OS was observed in both groups (isolated liver metastases group: 40.5 months; liver metastases and sarcomatosis group: 28.7 months; P = 0.620). CONCLUSIONS Overall survival in patients with GIST and metastatic disease to the liver and sarcomatosis is similar to that in patients with isolated metastatic liver disease. Although patients with a greater disease burden might be expected to show worse survival, these data do not reflect this assumption.
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Affiliation(s)
| | | | - Colin M Parsons
- Department of Sarcoma Oncology, Kaiser Permanente Health SystemsSan Diego, CA, USA
| | - Jonathan S Zager
- Department of Sarcoma Oncology, Moffitt Cancer CenterTampa, FL, USA
| | - Anthony P Conley
- Department of Sarcoma Oncology, Moffitt Cancer CenterTampa, FL, USA
| | - Ricardo J Gonzalez
- Department of Sarcoma Oncology, Moffitt Cancer CenterTampa, FL, USA,Correspondence Ricardo J. Gonzalez, Moffitt Cancer Center, MCC Sarcoma Program, 12902 Magnolia Drive, Tampa, FL 33612, USA. Tel: + 1 813 745 6161. Fax: + 1 813 745 8337. E-mail:
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Rammohan A, Sathyanesan J, Rajendran K, Pitchaimuthu A, Perumal SK, Srinivasan UP, Ramasamy R, Palaniappan R, Govindan M. A gist of gastrointestinal stromal tumors: A review. World J Gastrointest Oncol 2013; 5:102-112. [PMID: 23847717 PMCID: PMC3708046 DOI: 10.4251/wjgo.v5.i6.102] [Citation(s) in RCA: 116] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2013] [Revised: 04/30/2013] [Accepted: 06/10/2013] [Indexed: 02/05/2023] Open
Abstract
Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mesenchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularly-targeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.
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Kee D, Zalcberg JR. Current and emerging strategies for the management of imatinib-refractory advanced gastrointestinal stromal tumors. Ther Adv Med Oncol 2012; 4:255-70. [PMID: 22942908 DOI: 10.1177/1758834012450935] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Since its approval by the US Food and Drug Administration in February 2002, the tyrosine kinase inhibitor, imatinib, has become the standard of care for patients with metastatic or unresectable KIT-positive gastrointestinal stromal tumors (GISTs). Imatinib functions by blocking the adenosine triphosphate binding site of the constitutively activated mutant KIT or platelet-derived growth factor receptor α, effectively shutting down the oncogenic signal that drives up to 90% of these tumors. In doing so, it has transformed the management of a condition previously refractory to systemic treatments and established GIST as a model for the use of targeted therapies and oncogene addiction in solid tumors. However, while more than 80% of patients will receive clinical benefit from imatinib monotherapy, more than half will develop progressive disease by 2 years. In this article we review the mechanism and patterns of imatinib resistance in GIST; attempt to offer a practical schema for managing imatinib-refractory patients; and lastly, offer some insight as to future directions and emerging therapeutics for the management of this highly interesting and challenging disease.
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Affiliation(s)
- Damien Kee
- Department of Cancer Medicine, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, VIC 3002 and Department of Pathology, University of Melbourne, Parkville, VIC, Australia
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Abstract
Despite being the most common sarcoma of the gastrointestinal tract, gastrointestinal stromal tumor (GIST) has been widely recognized as a unique entity for just over a decade. The advent of tyrosine kinase inhibitors has revolutionized the diagnosis and treatment of GIST. Although surgery remains the only chance for cure, multimodal treatment that includes molecular therapy continues to develop. Optimal management of GIST requires careful radiographic, pathologic, medical, and surgical care, emphasizing the need for a multidisciplinary approach. This review highlights recent developments in the management of GIST.
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Affiliation(s)
- Zubin M Bamboat
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
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Gastrointestinal stromal tumours at present: an approach to burning questions. Clin Transl Oncol 2010; 12:100-12. [DOI: 10.1007/s12094-010-0476-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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