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Hohenberger P, Rathmann N, Büsing K, Menge F, Jakob J, Pink D, Wardelmann E, Schoenberg SO, Diehl SJ. Selective internal radiation with Y-90 resin microspheres (SIRT) for liver metastases of gastro-intestinal stromal tumors (GIST) resistant to tyrosine kinase inhibitor (TKI) therapy. Br J Cancer 2025; 132:716-724. [PMID: 40044980 PMCID: PMC11997030 DOI: 10.1038/s41416-025-02952-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 12/20/2024] [Accepted: 01/31/2025] [Indexed: 04/16/2025] Open
Abstract
BACKGROUND Hepatic metastases of GIST might be the dominant site of progression and resistant to available tyrosine kinase inhibitors (TKIs). Selective internal radiation therapy (SIRT) offers treatment by intratumoral radiation up to 200 Gy. We analyzed the hepatic progression-free survival (H-PFS) in a consecutive patient cohort. METHODS Twenty-six patients (median age 57.6 years) with biopsy proven liver metastases of GIST were treated by SIRT. All had RECIST documented tumor progression, and 24/26 patients had up to four lines of pretreatment. Mutational status was 'quadruple wildtype' (q-wt, n = 5), KIT exon 11/9/13 in n = 15/4/1 cases and PDGFRα (n = 1). Median follow-up of this retrospective analysis of a prospectively kept database is 33.6 months. RESULTS Median H-PFS was 16 months (range, 4-54+ months, 95% CI 6.5-25.4 months) and OS after SIRT was 28 months (95% CI 17.2-28.7 months). Best H-PFS was observed in patients with 'q-wt' at 25 months (range, 6+-54 months, 95% CI 16.2-33.8 months). The worst outcome was for KIT exon 11 mutations plus secondary mutations with 7 months (range, 4-33 months, 95% CI, 4.2-9.8 months). CONCLUSIONS 90Y-SIRT is a potent treatment for patients with liver metastases of GIST resistant to TKI therapy. In patients with 'q-wt' GIST, SIRT is an option for first-line use.
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Affiliation(s)
- Peter Hohenberger
- Division of Surgical Oncology and Thoracic Surgery, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Heidelberg, Germany.
| | - Nils Rathmann
- Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Heidelberg, Germany
| | - Karen Büsing
- Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Heidelberg, Germany
| | - Franka Menge
- Division of Surgical Oncology and Thoracic Surgery, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Heidelberg, Germany
| | - Jens Jakob
- Department of Surgery Mannheim University Medical Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Daniel Pink
- Sarkomzentrum Berlin-Brandenburg, HELIOS Klinikum Berlin-Buch, Berlin, Germany
| | - Eva Wardelmann
- Sarkomzentrum Berlin-Brandenburg, HELIOS Klinikum Berlin-Buch, Berlin, Germany
- Gerhard Domagk Institute of Pathology, University Hospital Muenster, Muenster, Germany
| | - Stefan O Schoenberg
- Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Heidelberg, Germany
| | - Steffen J Diehl
- Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim - Heidelberg University, Heidelberg, Germany
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Ecker BL, Maki RG, Cavnar MJ, DeMatteo RP. Surgical Management of Sarcoma Metastatic to Liver. Hematol Oncol Clin North Am 2025; 39:55-65. [PMID: 39510677 DOI: 10.1016/j.hoc.2024.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
Sarcomas are rare mesenchymal tumors with a propensity for hematogenous metastasis. Gastrointestinal stromal tumor (GIST) is the most common histologic subtype and the most common source of hepatic metastases. In the case of metastatic GIST, neoadjuvant imatinib can be used as a selection tool for the judicious application of surgery, where treatment-responsive patients who undergo resection to prevent the development of treatment-resistant clones have associated 10-year actuarial survival of 40%. Further advances for many of the non-GIST sarcoma subtypes will depend on the development of improved systemic therapies and evaluation of their activity in subtype or molecularly defined trials.
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Affiliation(s)
- Brett L Ecker
- Rutgers Cancer Institute, Rutgers Robert Wood Johnson Medical School, Cooperman Barnabas Medical Center 94 Old Short Hills Road, Suite 1172, Livingston, NJ 07039.
| | - Robert G Maki
- Department of Medicine, University of Pennsylvania, 3400 Spruce st, Philadelphia, PA 19104, USA
| | - Michael J Cavnar
- Department of Surgery, University of Kentucky, 800 Rose St First Floor, Lexington, KY 40536, USA
| | - Ronald P DeMatteo
- Rutgers Cancer Institute, Rutgers Robert Wood Johnson Medical School, Cooperman Barnabas Medical Center 94 Old Short Hills Road, Suite 1172, Livingston, NJ 07039
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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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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: 9] [Impact Index Per Article: 3.0] [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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Ecker BL, Maki RG, Cavnar MJ, DeMatteo RP. Surgical Management of Sarcoma Metastatic to Liver. Surg Oncol Clin N Am 2020; 30:57-67. [PMID: 33220809 DOI: 10.1016/j.soc.2020.08.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Sarcomas are rare mesenchymal tumors with a propensity for hematogenous metastasis. Gastrointestinal stromal tumor (GIST) is the most common histologic subtype and the most common source of hepatic metastases. In the case of metastatic GIST, neoadjuvant imatinib can be used as a selection tool for the judicious application of surgery, where treatment-responsive patients who undergo resection to prevent the development of treatment-resistant clones have associated 10-year actuarial survival of 40%. Further advances for many of the non-GIST sarcoma subtypes will depend on the development of improved systemic therapies and evaluation of their activity in subtype or molecularly defined trials.
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Affiliation(s)
- Brett L Ecker
- Department of Surgery, University of Pennsylvania, 3400 Spruce st, Philadelphia, PA 19104, USA.
| | - Robert G Maki
- Department of Medicine, University of Pennsylvania, 3400 Spruce st, Philadelphia, PA 19104, USA
| | - Michael J Cavnar
- Department of Surgery, University of Kentucky, 800 Rose St First Floor, Lexington, KY 40536, USA
| | - Ronald P DeMatteo
- Department of Surgery, University of Pennsylvania, 3400 Spruce st, Philadelphia, PA 19104, USA
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8
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Herren JL, Disomma N, Ray CE. Hepatocellular Carcinoma: Combined Transarterial Chemoembolization and Ablation. Semin Intervent Radiol 2019; 36:279-284. [PMID: 31435137 PMCID: PMC6699963 DOI: 10.1055/s-0039-1694066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- Josi L. Herren
- Department of Radiology, University of Illinois College of Medicine, Chicago, Illinois
| | - Nerina Disomma
- Department of Radiology, University of Illinois College of Medicine, Chicago, Illinois
| | - Charles E. Ray
- Department of Radiology, University of Illinois College of Medicine, Chicago, Illinois
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Schrage Y, Hartgrink H, Smith M, Fiore M, Rutkowski P, Tzanis D, Messiou C, Servois V, Bonvalot S, van der Hage J. Surgical management of metastatic gastrointestinal stromal tumour. Eur J Surg Oncol 2018; 44:1295-1300. [DOI: 10.1016/j.ejso.2018.06.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 06/04/2018] [Indexed: 12/12/2022] Open
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Sanchez-Hidalgo JM, Duran-Martinez M, Molero-Payan R, Rufian-Peña S, Arjona-Sanchez A, Casado-Adam A, Cosano-Alvarez A, Briceño-Delgado J. Gastrointestinal stromal tumors: A multidisciplinary challenge. World J Gastroenterol 2018; 24:1925-1941. [PMID: 29760538 PMCID: PMC5949708 DOI: 10.3748/wjg.v24.i18.1925] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 04/27/2018] [Accepted: 05/06/2018] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. Its usual manifestation is gastrointestinal bleeding. However, small asymptomatic lesions are frequently detected as incidental finding. Characteristically, most GISTs (> 95%) are positive for the KIT protein (CD117) by IHC staining and approximately 80%-90% of GISTs carry a mutation in the c-KIT or PDGFRA genes. Mutational analysis should be performed when planning adjuvant and neoadjuvant therapy, due to its possible resistance to conventional treatment. The arise of tyrosine kinase inhibitor has supposed a revolution in GISTs treatment being useful as adjuvant, neoadjuvant or recurrence disease treatment. That is why a multidisciplinary approach to this disease is required. The correct characterization of the tumor at diagnosis (the diagnosis of recurrences and the evaluation of the response to treatment with tyrosine kinase inhibitors) is fundamental for facing these tumors and requires specialized Endoscopist, Radiologists and Nuclear Medicine Physician. Surgery is the only potentially curative treatment for suspected resectable GIST. In the case of high risk GISTs, surgery plus adjuvant Imatinib-Mesylate for 3 years is the standard treatment. Neoadjuvant imatinib-mesylate should be considered to shrink the tumor in case of locally advanced primary or recurrence disease, unresectable or potentially resectable metastasic tumors, and potentially resectable disease in complex anatomic locations to decrease the related morbidity. In the case of Metastatic GIST under Neoadjuvant treatment, when there are complete response, stable disease or limited disease progression, complete cytoreductive surgery could be a therapeutic option if feasible.
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Affiliation(s)
- Juan Manuel Sanchez-Hidalgo
- Department of General and Digestive Surgery, Reina Sofia University Hospital, Avda. Menéndez Pidal s/n, Cordoba 14004, Spain
| | - Manuel Duran-Martinez
- Department of General and Digestive Surgery, Reina Sofia University Hospital, Avda. Menéndez Pidal s/n, Cordoba 14004, Spain
| | - Rafael Molero-Payan
- Department of Intern Medicine, Reina Sofia University Hospital, Avda. Menéndez Pidal s/n, Cordoba 14004, Spain
- Lipids and Atherosclerosis Research Unit, IMIBIC/Hospital Universitario Reina Sofía/Universidad de Córdoba, Cordoba 14004, Spain
| | - Sebastian Rufian-Peña
- Department of General and Digestive Surgery, Reina Sofia University Hospital, Avda. Menéndez Pidal s/n, Cordoba 14004, Spain
| | - Alvaro Arjona-Sanchez
- Department of General and Digestive Surgery, Reina Sofia University Hospital, Avda. Menéndez Pidal s/n, Cordoba 14004, Spain
| | - Angela Casado-Adam
- Department of General and Digestive Surgery, Reina Sofia University Hospital, Avda. Menéndez Pidal s/n, Cordoba 14004, Spain
| | - Antonio Cosano-Alvarez
- Department of General and Digestive Surgery, Reina Sofia University Hospital, Avda. Menéndez Pidal s/n, Cordoba 14004, Spain
| | - Javier Briceño-Delgado
- Department of General and Digestive Surgery, Reina Sofia University Hospital, Avda. Menéndez Pidal s/n, Cordoba 14004, Spain
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Liu Q, Kong F, Zhou J, Dong M, Dong Q. Management of hemorrhage in gastrointestinal stromal tumors: a review. Cancer Manag Res 2018; 10:735-743. [PMID: 29695930 PMCID: PMC5903846 DOI: 10.2147/cmar.s159689] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are relatively common mesenchymal tumors. They originate from the wall of hollow viscera and may be found in any part of the digestive tract. The prognosis of patients with stromal tumors depends on various risk factors, including size, location, presence of mitotic figures, and tumor rupture. Emergency surgery is often required for stromal tumors with hemorrhage. The current literature suggests that stromal tumor hemorrhage indicates poor prognosis. Although the optimal treatment options for hemorrhagic GISTs are based on surgical experience, there remains controversy with regard to optimum postoperative management as well as the classification of malignant potential. This article reviews the biological characteristics, diagnostic features, prognostic factors, treatment, and postoperative management of GISTs with hemorrhage.
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Affiliation(s)
- Qi Liu
- Department of Gastrointestinal Surgery, The First Hospital, China Medical University, Shenyang, China
| | - Fanmin Kong
- Department of Gastrointestinal Surgery, The First Hospital, China Medical University, Shenyang, China
| | - Jianping Zhou
- Department of Gastrointestinal Surgery, The First Hospital, China Medical University, Shenyang, China
| | - Ming Dong
- Department of Gastrointestinal Surgery, The First Hospital, China Medical University, Shenyang, China
| | - Qi Dong
- Department of General Surgery, The People's Hospital, China Medical University, Shenyang, China
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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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Lim KT, Tan KY. Current research and treatment for gastrointestinal stromal tumors. World J Gastroenterol 2017; 23:4856-4866. [PMID: 28785140 PMCID: PMC5526756 DOI: 10.3748/wjg.v23.i27.4856] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 05/11/2017] [Accepted: 06/18/2017] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest, especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene, BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential, and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure, targeted therapy in the form of tyrosine kinase inhibitors (TKIs) has revolutionized the management options. As the first-line TKI, imatinib offers treatment for advanced and metastatic GISTs, adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options, including prolonging the first-line TKI from 1 to 3 years, increasing the dose of TKI or switching to second-line TKI. Other newer TKIs, such as sunitinib and regorafenib, may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated, such as inhibitors of BRAF, heat shock protein 90, glutamine and mitogen-activated protein kinase signaling, as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe, North America and Asia are highlighted.
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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: 102] [Impact Index Per Article: 12.8] [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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15
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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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Kanda T, Ishikawa T, Kosugi SI, Ueki K, Naito T, Wakai T, Hirota S. Prognostic factors after imatinib secondary resistance: survival analysis in patients with unresectable and metastatic gastrointestinal stromal tumors. Int J Clin Oncol 2015; 21:295-301. [PMID: 26386705 DOI: 10.1007/s10147-015-0903-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Accepted: 09/03/2015] [Indexed: 01/26/2023]
Abstract
BACKGROUND Patients undergoing imatinib therapy for gastrointestinal stromal tumors (GISTs) show drug resistance during treatment in the late stages. The aims of this study were to determine survival after the appearance of imatinib secondary resistance (ISR) and to identify the prognostic factors. METHODS Eligible were patients with unresectable and metastatic GISTs who were diagnosed with ISR and/or underwent treatment for ISR in our institution between 2001 and 2012. A total of 48 patients were enrolled and overall survival was retrospectively analyzed. The Cox proportional hazards model was used to identify the independent prognostic factors. Median follow-up time was 58 months. RESULTS As of the cutoff date, 41 of the 48 patients with ISR had died, of which 39 died of GISTs. The overall 1-, 3-, and 5-year survival rates of the 48 patients were 64.6, 32.8, and 20.4 %, respectively, and median survival time was 22 months. The favorable independent prognostic factors identified were long progression-free survival in first-line imatinib therapy (P = 0.04), small diameter of progressive disease (PD) (P = 0.02), and surgical resection of PD (P = 0.01). CONCLUSION Surgical resection of PD in selected cases could improve prognosis in ISR patients undergoing GIST treatment.
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Affiliation(s)
- Tatsuo Kanda
- Department of Surgery, Sanjo General Hospital, 5-Tsukanome, Sanjo, Niigata, 955-0055, Japan.
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Takashi Ishikawa
- Department of Medical Informatics, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Shin-Ichi Kosugi
- Department of Digestive and General Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Minami-Uonuma, Niigata, Japan
| | - Kyo Ueki
- Department of Surgery, Kashiwazaki Medical Center, Kashiwazaki, Niigata, Japan
| | - Tetsuya Naito
- Department of Surgery, Nagaoka Red Cross Hospital, Nagaoka, Niigata, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Seiichi Hirota
- Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
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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: 24] [Impact Index Per Article: 2.4] [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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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; 26:124-131. [PMID: 24653635 PMCID: PMC3937743 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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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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Pereira PR, Odashiro AN, Lim LA, Miyamoto C, Blanco PL, Odashiro M, Maloney S, De Souza DF, Burnier MN. Current and emerging treatment options for uveal melanoma. Clin Ophthalmol 2013; 7:1669-82. [PMID: 24003303 PMCID: PMC3755706 DOI: 10.2147/opth.s28863] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults, with a 10-year cumulative metastatic rate of 34%. The most common site of metastasis is the liver (95%). Unfortunately, the current treatment of metastatic UM is limited by the lack of effective systemic therapy. Options for the management of the primary intraocular tumor include radical surgery as well as conservative treatments in order to preserve visual acuity. For metastatic disease, several approaches have been described with no standard method. Nevertheless, median survival after liver metastasis is poor, being around 4–6 months, with a 1-year survival of 10%–15%. In this review, the authors summarize current and promising new treatments for UM.
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Affiliation(s)
- Patricia Rusa Pereira
- The Henry C Witelson Ocular Pathology Laboratory, McGill University, Montreal, QC, Canada
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Farshid P, Darvishi A, Naguib N, Bazrafshan B, Paul J, Mbalisike E, Vogl TJ. Repetitive chemoembolization of hypovascular liver metastases from the most common primary sites. Future Oncol 2013; 9:419-26. [PMID: 23469977 DOI: 10.2217/fon.12.191] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
AIM To evaluate tumor response in patients with hypovascular liver metastases from the most common primary sites treated with chemoembolization. MATERIALS & METHODS Chemoembolization was performed in 190 patients (five groups) who had hypovascular liver metastases from the colon (n = 66), breast (n = 40), uveal malignant melanoma (n = 20), pancreas (n = 48) and stomach (n = 16). Surgical resection of primary sites had been performed for all included patients. Tumor response, survival statistics from the first chemoembolization using Kaplan-Meier method and progression rate of embolized lesions were evaluated by analysis of variance with Tukey's post hoc test. RESULTS Multiple comparison between the groups showed no statistical significant difference in local tumor response (H: 9.23; p > 0.05). Survival indices of the patients, including survival rate, progression-free survival rate, median survival time and time to progression, demonstrated significant difference between the groups during the follow-up period (H: 9.7; p = 0.045). The progression rate of treated liver metastases from colon, breast, uvea, pancreas and stomach were 16.6, 17.5, 30.0, 25.0 and 32.0%, respectively (p = 0.002). CONCLUSION Hypovascular liver metastases treated with chemoembolization may demonstrate equal local response, but are significantly different in rate of progression and survival.
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Affiliation(s)
- Parviz Farshid
- Department of Radiology, Marienhospital Osnabrueck, Bischofsstrasse 1, 49074 Osnabrueck, Germany.
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Cao G, Li J, Shen L, Zhu X. Transcatheter arterial chemoembolization for gastrointestinal stromal tumors with liver metastases. World J Gastroenterol 2012; 18:6134-6140. [PMID: 23155343 PMCID: PMC3496891 DOI: 10.3748/wjg.v18.i42.6134] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2012] [Revised: 08/28/2012] [Accepted: 10/19/2012] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) for gastrointestinal stromal tumor (GIST) with liver metastases after the failure of tyrosine kinase inhibitors (TKIs). METHODS Patients with histologically confirmed CD117-positive GIST with liver metastases who were resistant and/or intolerant to prior imatinib and/or sunitinib and who received TACE for at least one treatment cycle or only best supportive care and TKI reintroduction were eligible for the study. The patients were divided into two groups: those in TACE group received TACE treatment containing 5-20 mL iodized oil and 40-80 mg doxorubicin hydrochloride and TKI reintroduction or best supportive care, those in control group only received TKI reintroduction or best supportive care. The primary end-point was overall survival and the secondary end-points were, progression-free survival (PFS), response rates, and safety. RESULTS Sixty patients admitted between June 2008 and October 2011 were eligible for this study, including 22 in TACE group and 38 in control group. In the TACE group, 12 (54.5%) achieved liver partial response, 5 (22.7%) had stable disease, and 5 (22.7%) had liver progressive disease. Disease control rate of liver metastases was 77.3% in the TACE group and 39.5% in the control group. The median liver PFS in TACE group was 47.1 wk (95% CI: 23.9-70.3). The median PFS in TACE group was longer than in control group (30.0 wk, 95% CI: 20.1-39.9 vs 12.9 wk, 95% CI: 11.9-13.9) (P = 0.0001). The median overall survival in TACE group was also longer than in control group (68.5 wk, 95% CI: 57.4-79.6 vs 25.7 wk, 95% CI: 23.2-28.2) (P = 0.0001). TACE treatment significantly reduced the risk of death (hazard ratio: 0.109). Patients without extrahepatic metastases treated with TACE had significantly better prognosis. Most of the adverse events were of grade 1 or 2 and tolerable. CONCLUSION TACE is effective and well tolerated in GIST patients with liver metastases after TKI failure, and it may be an optional treatment for this disease.
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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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25
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Qian J. Interventional therapies of unresectable liver metastases. J Cancer Res Clin Oncol 2011; 137:1763-72. [PMID: 21909952 DOI: 10.1007/s00432-011-1026-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2011] [Accepted: 07/28/2011] [Indexed: 11/26/2022]
Abstract
Liver metastases are the major cause of mortality in patients with gastrointestinal carcinomas and other malignant tumors, carrying a poor prognosis and presenting considerable management. Surgical resection remains the only curative therapy for liver metastases up to now. However, only a small percentage of patients are suitable for curative resection due to many factors: multi-centric tumors, extrahepatic metastases, early vascular invasion, and coexisting advanced liver cirrhosis. In non-surgical cases, regional interventional therapies have led to a major break through in the treatment of unresectable liver metastases, which include transarterial chemoembolization (TACE), radiofrequency ablation (RFA), laser-induced thermotherapy (LITT), cryosurgical ablation (CSA), microwave coagulation therapy (MCT), percutaneous ethanol injection (PEI), and others. As a result of the technical development of locoregional approaches for unresectable liver metastases during recent decades, the range of combined interventional therapies has been continuously enlarged. The current roles of these treatment options for liver metastases are discussed in this review.
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Affiliation(s)
- Jun Qian
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road. 1277, Wuhan, 430022, People's Republic of China.
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Ahrar J, Gupta S, Ensor J, Ahrar K, Madoff DC, Wallace MJ, Murthy R, Tam A, Hwu P, Bedikian AY. Response, survival, and prognostic factors after hepatic arterial chemoembolization in patients with liver metastases from cutaneous melanoma. Cancer Invest 2011; 29:49-55. [PMID: 21166498 DOI: 10.3109/07357907.2010.535052] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
We reviewed the medical records of 42 patients with cutaneous melanoma metastatic to the liver who underwent hepatic artery chemoembolization (HACE) at our institution. HACE resulted in radiologic response (38.9%) or disease stabilization (47.2%) in most patients. The median overall survival (OS) and time to progression (TTP) of liver disease were 7.7 and 6 months, respectively. Patient's age, lactate dehydrogenase (LDH) levels, type of treatment, number of extrahepatic metastatic sites, and response to therapy were found to be significant predictors of OS after HACE. Prolonged survival was seen in patients who responded to HACE (p = .034).
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Affiliation(s)
- Judy Ahrar
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
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Hepatic artery chemoembolization in patients with ocular melanoma metastatic to the liver: response, survival, and prognostic factors. Am J Clin Oncol 2010; 33:474-80. [PMID: 19935383 DOI: 10.1097/coc.0b013e3181b4b065] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Although hepatic arterial chemoembolization (HACE) has been used for treatment of ocular melanoma metastatic to the liver, the prognostic indicators for survival after HACE have not been studied. We evaluated response rates and survival durations after HACE in such patients and analyzed factors affecting their survival. METHODS The medical records of patients with ocular melanoma metastatic to liver who underwent HACE at our institution from 1992 to 2005 were reviewed. The radiologic tumor response rates, and overall survival (OS) and progression-free survival durations were calculated, and patient, tumor, and treatment variables were analyzed to identify factors influencing survival. RESULTS One hundred twenty-five patients underwent 265 HACE sessions. Of 105 patients in whom radiologic responses could be evaluated, 12 (11%) had partial responses, 17 (16%) had minor responses, 68 (65%) had stable disease, and 8 (8%) had progressive disease. The median OS and progression-free survival durations were 6.7 and 3.8 months, respectively. Multivariate analysis showed that >75% liver involvement and high lactate dehydrogenase levels were associated with short OS. Patients who had radiologic responses to HACE had a longer median OS duration than did patients who did not (15.8 vs. 6.1 months; P = 0.0005). Patients with >75% liver involvement had a median OS duration of only 2.4 months. CONCLUSIONS HACE resulted in radiologic response or disease stabilization in most patients with ocular melanomas metastatic to the liver. The extent of liver involvement, baseline lactate dehydrogenase levels, and response to therapy were found to be significant predictors of OS after HACE.
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Demetri GD, von Mehren M, Antonescu CR, DeMatteo RP, Ganjoo KN, Maki RG, Pisters PWT, Raut CP, Riedel RF, Schuetze S, Sundar HM, Trent JC, Wayne JD. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw 2010; 101:442. [PMID: 20457867 DOI: 10.1002/jso.21485] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic accuracy and led to the discovery of novel immunomarkers and new mechanisms of resistance to TKI therapy, which in turn have resulted in the development of novel treatment strategies. To address these issues, the NCCN organized a task force consisting of a multidisciplinary panel of experts in the fields of medical oncology, surgical oncology, molecular diagnostics, and pathology to discuss the recent advances, identify areas of future research, and recommend an optimal approach to care for patients with GIST at all stages of disease. The task force met for the first time in October 2003 and again in December 2006 and October 2009. This supplement describes the recent developments in the field of GIST as discussed at the October 2009 meeting.
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Kamusella PC, Bethke A, Platzek I, Wiggermann P, Wissgott C, Stroszczynski C. [Minimally invasive management of metastases from gastrointestinal stromal tumors]. Radiologe 2010; 49:1132-5. [PMID: 19820910 DOI: 10.1007/s00117-009-1855-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Minimally invasive radiological procedures can lead to an improvement in the prognosis and the clinical symptoms in cases of metastases of gastro-intestinal stromal tumors (GIST) in the context of multimodal therapy concepts. In the context of interdisciplinary therapy decision-making radiofrequency ablation (RFA) and transarterial tumor embolization should be considered.
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Affiliation(s)
- P C Kamusella
- Radiologisches Institut, Universitätsklinikum Dresden, Fetscherstrasse 74, Dresden, Germany.
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Demetri GD, von Mehren M, Antonescu CR, DeMatteo RP, Ganjoo KN, Maki RG, Pisters PWT, Raut CP, Riedel RF, Schuetze S, Sundar HM, Trent JC, Wayne JD. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw 2010; 8 Suppl 2:S1-41; quiz S42-4. [PMID: 20457867 PMCID: PMC4103754 DOI: 10.6004/jnccn.2010.0116] [Citation(s) in RCA: 814] [Impact Index Per Article: 54.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic accuracy and led to the discovery of novel immunomarkers and new mechanisms of resistance to TKI therapy, which in turn have resulted in the development of novel treatment strategies. To address these issues, the NCCN organized a task force consisting of a multidisciplinary panel of experts in the fields of medical oncology, surgical oncology, molecular diagnostics, and pathology to discuss the recent advances, identify areas of future research, and recommend an optimal approach to care for patients with GIST at all stages of disease. The task force met for the first time in October 2003 and again in December 2006 and October 2009. This supplement describes the recent developments in the field of GIST as discussed at the October 2009 meeting.
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Abstract
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract with malignant potential. Because of the lack of specific clinical manifestations, an accurate preoperative diagnosis of GIST is very difficult. In recent years, the pathogenesis of GIST has been gradually clarified, and their diagnosis and treatment have been greatly improved. Oncogenic mutation of the KIT receptor tyrosine kinase is found in the majority of patients with GIST. Immunohistochemical detection of markers such as CD117 is key to the diagnosis of GIST. Although combined therapy has been emphasized recently, radical surgical treatment is still the most effective option for GIST. Postoperative molecular targeted therapies, including neoadjuvant therapy and adjuvant therapy, can greatly improve the outcomes of patients with GIST. The development of imatinib offers new hope to patients with GIST.
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Hepatic arterial embolization and chemoembolization for imatinib-resistant gastrointestinal stromal tumors. Am J Clin Oncol 2009; 32:574-81. [PMID: 19636238 DOI: 10.1097/coc.0b013e31819cca35] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES We evaluated the efficacy of embolotherapy including hepatic arterial embolization and chemoembolization in patients with imatinib-resistant gastrointestinal stromal tumors with progressive liver metastases. METHODS Medical records and computed tomography images of patients with imatinib-resistant gastrointestinal stromal tumor with progressive liver metastases who underwent embolotherapy from January 2002 through January 2007 were retrospectively reviewed. Response was assessed by Response Evaluation Criteria in Solid Tumors and modified CT response criteria that assessed tumor density changes. Progression-free survival in the liver and overall survival rates were calculated from the date of the initial embolotherapy session using the Kaplan-Meier method. Correlations between disease status or treatment variables and survival were tested in univariate and multivariate analyses using the log-rank test, and the Cox proportional hazards model, respectively. RESULTS Fourteen patients with gastrointestinal stromal tumor who had been treated with imatinib for 7 to 61 months underwent 26 sessions of embolotherapy. Radiologic response could be evaluated in 13 patients. On the basis of response evaluation criteria in solid tumors, 1 patient demonstrated a partial response and the remaining 12 patients demonstrated stable disease. On the basis of the modified CT response criteria, 7 patients demonstrated a partial response and 6 patients demonstrated stable disease. Progression-free survival rates in the liver were 78.7%, 31.4%, and 31.4% at 6 months, 1, and 3 years, respectively; the median progression-free survival time was 7.0 months. Overall survival rates were 78.6%, 45.8%, and 45.8% at 6 month, 1 year, and 3 year, respectively; the median overall survival time was 9.7 months. Patients who had progressive extrahepatic metastases at the time of treatment and those who received only 1 embolotherapy treatment had shorter OS than did patients with liver-only progression and those who received 2 or more treatment sessions, respectively. CONCLUSIONS Hepatic arterial embolization and chemoembolization induced radiologic response or disease stabilization in most patients with imatinib-resistant gastrointestinal stromal tumor with progressive liver metastases. Patients with progressive extrahepatic metastases or those who are not amenable to more than 1 embolotherapy sessions, however, did not demonstrate an appreciable survival benefit following embolotherapy.
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Gramza AW, Corless CL, Heinrich MC. Resistance to Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors. Clin Cancer Res 2009; 15:7510-7518. [PMID: 20008851 DOI: 10.1158/1078-0432.ccr-09-0190] [Citation(s) in RCA: 168] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Gastrointestinal stromal tumors (GIST) are the most common type of sarcoma in the gastrointestinal tract. Surgery is the primary treatment modality, but many patients suffer disease recurrence or metastasis. Fortunately, the management of advanced GIST has been revolutionized by the use of small molecule kinase inhibitors that target the underlying pathogenetic mutant kinases found in the vast majority of cases. Approximately 85% of GISTs have oncogenic mutations in KIT, allowing for constitutive kinase activation that is responsible for cellular proliferation and survival. About 5 to 7% of GISTs have activating mutations of the homologous platelet-derived growth factor receptor alpha (PDGFRA) kinase. The progression-free and overall survival of patients with advanced disease is greatly improved by treatment with the kinase inhibitors imatinib and sunitinib. However, the emergence of drug-resistant tumor clones limits the long-term benefit of these drugs in most patients. Resistance to these kinase inhibitors is associated with distinctive clinical and molecular features, with the development of secondary mutations of the oncogenic kinase being the most common mechanism. We review the molecular basis of GIST response and/or resistance to TKIs, and discuss strategies to prevent and/or overcome drug resistance. These concepts are directly relevant to the development of targeted molecular therapy for other solid tumors. (Clin Cancer Res 2009;15(24):7510-8).
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Affiliation(s)
- Ann W Gramza
- Authors' Affiliations: Portland VA Medical Center and Oregon Health and Science University Knight Cancer Institute, Portland, Oregon
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Abstract
GIST (gastrointestinal stromal tumor) is a rare soft tissue malignancy arising in the gut. It has become well known recently because of the effectiveness of anti-KIT tyrosine kinase inhibitors. From a disease that 10 years ago was only treatable with surgery, now multiple phase 2 and phase 3 trials have identified active first-line systemic therapy, appropriate dosing, an active second-line agent, and established the role of adjuvant therapy after surgery for patients with intermediate- and high-risk tumors. These are accomplishments that took decades to achieve for other more common diseases such as breast cancer or lung cancer. GIST has been the ideal disease system for studying targeted therapy in solid tumors. The progress in treating GIST has come directly from the advances that have been made in the laboratory, understanding the basic biology of tyrosine kinases, the oncogenic activity of c-KIT, and how that enzymatic activity can be inhibited. By studying model diseases such as GIST, we should be able to develop paradigms to treat more common cancers as well.
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Affiliation(s)
- David D'Adamo
- Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Yamamoto A, Chervoneva I, Sullivan KL, Eschelman DJ, Gonsalves CF, Mastrangelo MJ, Berd D, Shields JA, Shields CL, Terai M, Sato T. High-dose immunoembolization: survival benefit in patients with hepatic metastases from uveal melanoma. Radiology 2009; 252:290-8. [PMID: 19561263 DOI: 10.1148/radiol.2521081252] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
PURPOSE To retrospectively evaluate prognostic factors for survival in patients with uveal melanoma who received chemoembolization (CE) with 1,3-bis (2-chloroethyl)-1-nitrosourea or immunoembolization (IE) with granulocyte-macrophage colony-stimulating factor (GM-CSF) for hepatic metastases. MATERIALS AND METHODS Fifty-three consecutive patients with uveal melanoma were treated by using CE or IE in clinical trials approved by the Institutional Review Board. Prognostic factors associated with overall survival (OS) and progression-free survival (PFS) in the liver and extrahepatic (systemic) organs were retrospectively evaluated. Covariates of age, sex, preexisting extrahepatic metastases, liver enzyme levels, tumor volume, radiologic response in hepatic metastases, and treatment type were analyzed. RESULTS Compared with CE, high-dose (>or=1500 microg of GM-CSF) IE resulted in significantly better OS (20.4 vs 9.8 months, P = .005) and systemic PFS (12.4 vs 4.8 months, P = .001) at univariate analysis. Overall, women outlived men (14.4 vs 9.8 months, P = .01). Patients who achieved regression of hepatic metastases after embolization lived much longer than did those who did not achieve regression (27.2 vs 9.9 months, P < .001). At multivariate analysis, prolonged OS was confirmed for women, patients who underwent high-dose IE, younger patients (age < 60 years), and patients with regression of hepatic metastases. Independent predictors of longer systemic PFS included high-dose IE, younger age, and regression of hepatic metastases. No covariate predicted liver PFS except for hepatic response. CONCLUSION Treatment with high-dose IE prolonged survival of patients with uveal melanoma who received embolization of hepatic metastases and possibly delayed progression of extrahepatic metastases.
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Affiliation(s)
- Akira Yamamoto
- Department of Medical Oncology, Jefferson Medical College, Thomas Jefferson University, 1025 Walnut St, Philadelphia, PA 19107, USA
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Fernández JA, Parrilla P. Tratamiento quirúrgico del GIST avanzado en la era del imatinib. Cir Esp 2009; 86:3-12. [DOI: 10.1016/j.ciresp.2008.09.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2008] [Accepted: 09/22/2008] [Indexed: 12/15/2022]
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Avritscher R, Gupta S. Gastrointestinal stromal tumor: role of interventional radiology in diagnosis and treatment. Hematol Oncol Clin North Am 2009; 23:129-37, ix. [PMID: 19248976 DOI: 10.1016/j.hoc.2008.11.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. The interventional radiologist plays an important role in the diagnosis and locoregional therapy for metastatic GISTs. Radiofrequency ablation (RFA) is a potentially curative option for patients exhibiting partial response to imatinib with focal residual disease. RFA can also be used for local control of focal hepatic or peritoneal metastasis. Hepatic embolization or chemoembolization is reserved for the treatment of progressive liver disease in imatinib-resistant patients who are not suitable for sunitinib as a second-line therapy.
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Affiliation(s)
- Rony Avritscher
- Department of Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 325, Houston, TX 77030, USA.
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Kingham TP, DeMatteo RP. Multidisciplinary treatment of gastrointestinal stromal tumors. Surg Clin North Am 2009; 89:217-33, x. [PMID: 19186237 DOI: 10.1016/j.suc.2008.10.003] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Gastrointestinal stromal tumor (GIST) has been recognized as a unique tumor only in the last decade. Although rare as a clinical entity, there is much interest in the pathology and treatment because the KIT protooncogene mutation common to most GISTs can be inhibited by imatinib mesylate. Diagnosing and treating GIST requires a multidisciplinary approach, given the combination of pathologic and radiographic evaluation, surgical treatment, and oncologic care required to successfully treat patients with GIST.
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Affiliation(s)
- T Peter Kingham
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, 303 E. 60th Street, Apt 28E, NY, NY 10022, USA.
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Abstract
The management of advanced gastrointestinal stromal tumor is increasingly complex because of imatinib refractory disease. Primary resistance to imatinib is uncommon, and most patients progress after development of additional genetic changes. This article reviews management strategies including surgical approaches, local modalities for progressive liver metastases, as well as novel therapeutic agents.
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Affiliation(s)
- Neeta Somaiah
- Fellow, Hematology Oncology, Fox Chase Cancer Center, Philadelphia, PA, , Add: 333 Cottman Ave., Philadelphia, PA-19111, Tel: 215 728-3545, Fax: 215 728-3639
| | - Margaret von Mehren
- Director, Sarcoma Oncology, Fox Chase Cancer Center, , Add: 333 Cottman Ave., Philadelphia, PA-19111, Tel: 215 728-2674, Fax: 215 728-3639
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Diagnosis and multi-disciplinary management of hepatic metastases from gastrointestinal stromal tumour (GIST). Eur J Surg Oncol 2009; 35:787-92. [PMID: 19185444 DOI: 10.1016/j.ejso.2009.01.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2008] [Revised: 12/25/2008] [Accepted: 01/06/2009] [Indexed: 12/13/2022] Open
Abstract
AIM To explore the present application of diagnosis and management of hepatic metastases from GIST. METHODS We performed a systematic review of the literature for studies concerning hepatic metastases from GIST. A literature search was performed using the Medline/PubMed databases to identify publications relevant to the review published from January 1998 to December 2008. Totally 113 relevant articles were retrieved. Abstracts from recent ASCO symposia were hand searched for relevant articles. After the primary filtration, articles on review and with repetitive content were excluded. The articles on clinical research, which were issued in authorized journals, were selected. At last, totally 69 articles were included for review. FINDINGS The rate of liver metastases was reported as 15.9% in primary GISTs. The recurrence rate following surgical resection for hepatic metastases from GIST had been reported as 70-77%. For metastatic GIST patients with tyrosine kinase inhibitor (TKI) treatment, it demonstrated rates of CR, PR and SD respectively of 5.84%, 50.7%, and 32.4%. Combining repeated surgery with TKI treatment, R0/R1 resection rates range in various series between 48 and 82%. For those patients with unresectable disease confined to the liver or unable to tolerate liver resection due to co-morbidity or advanced age, RFA, HACE, TKI therapy, or even liver transplantation, can also improve survival. CONCLUSIONS The liver is a common metastatic site for gastrointestinal stromal tumour (GIST). Appropriate initial evaluation remains paramount for selecting the correct management strategy. Multi-disciplinary management (which includes pathology, medical oncology, surgical oncology, and imaging expertise) of this disease is important for both curative and palliative treatment in these patients. Combining repeated surgery with TKI treatment may be the most effective management for GIST patients with liver metastases.
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Gupta P, Roy S, Singh OP, Rastogi H. Current Relevance of Hepatic Arterial Therapy (HAT) in the Era of Routine Molecular Targeted Therapy for Treatment of Hepatic Malignancy-A Practice Based Approach. APOLLO MEDICINE 2008. [DOI: 10.1016/s0976-0016(11)60483-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022] Open
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Choi EA, Abdalla EK. Patient selection and outcome of hepatectomy for noncolorectal non-neuroendocrine liver metastases. Surg Oncol Clin N Am 2008; 16:557-77, ix. [PMID: 17606194 DOI: 10.1016/j.soc.2007.04.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Improved patient selection, introduction of more effective systemic treatments including targeted biologic and combined therapies, and the low morbidity and mortality rates of hepatobiliary surgery in centers of excellence are likely to provide continued improvements in outcomes for patients with noncolorectal non-neuroendocrine liver metastases. Further advances in treatment may emerge from better understanding of the underlying tumor biology for each cancer type and application of individualized care to each patient.
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Affiliation(s)
- Eugene A Choi
- The University of Texas M. D. Anderson Cancer Center, Department of Surgical Oncology, 1515 Holcombe Boulevard, Unit 444, Houston, TX 77030, USA
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Kamat PP, Gupta S, Ensor JE, Murthy R, Ahrar K, Madoff DC, Wallace MJ, Hicks ME. Hepatic Arterial Embolization and Chemoembolization in the Management of Patients with Large-Volume Liver Metastases. Cardiovasc Intervent Radiol 2007; 31:299-307. [DOI: 10.1007/s00270-007-9186-3] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2007] [Revised: 06/25/2007] [Accepted: 09/10/2007] [Indexed: 12/01/2022]
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Liver embolizations in oncology: A review. Med Oncol 2007; 25:1-11. [DOI: 10.1007/s12032-007-0039-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2007] [Accepted: 05/20/2007] [Indexed: 02/08/2023]
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Abstract
PURPOSE OF REVIEW Most gastrointestinal stromal tumors eventually acquire resistance to imatinib mesylate. This review focuses on recent progress on management of patients whose disease progresses on the standard dose of imatinib. RECENT FINDINGS Approximately 30% of patients failing standard-dose imatinib achieve disease stabilization with high-dose imatinib, but objective responses are few and the clinical benefit usually short-lived. Patients receiving enzyme-inducing drugs may need high imatinib doses to achieve therapeutic blood concentrations. Surgical excision of a single growing metastasis leads to a median progression-free survival time of 7-11 months. Sunitinib malate is effective following imatinib failure. The median time to disease progression is approximately 6 months with sunitinib therapy versus 6 weeks with placebo following discontinuation of imatinib, but few (5%) patients achieve objective response. Patients with gastrointestinal stromal tumor with KIT exon 9 mutation may benefit more from sunitinib than those with exon 11 mutation. Sunitinib frequently causes abnormal thyroid function. SUMMARY Sunitinib is now the approved second line therapy following imatinib failure and for patients intolerant to imatinib. The clinical benefit is only moderate, and thyroid function monitoring is required. Several investigational agents are being evaluated for imatinib-resistant gastrointestinal stromal tumor. Palliative procedures, such as hepatic arterial embolization, also require study.
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Affiliation(s)
- Heikki Joensuu
- Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
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Abstract
Gastrointestinal stromal tumours are the most common mesenchymal neoplasm of the gastrointestinal tract and are highly resistant to conventional chemotherapy and radiotherapy. Such tumours usually have activating mutations in either KIT (75-80%) or PDGFRA (5-10%), two closely related receptor tyrosine kinases. These mutations lead to ligand-independent activation and signal transduction mediated by constitutively activated KIT or PDGFRA. Targeting these activated proteins with imatinib mesylate, a small-molecule kinase inhibitor, has proven useful in the treatment of recurrent or metastatic gastrointestinal stromal tumours and is now being tested as an adjuvant or neoadjuvant. However, resistance to imatinib is a growing problem and other targeted therapeutics such as sunitinib are available. The important interplay between the molecular genetics of gastrontestinal stromal tumour and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumours.
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Affiliation(s)
- Brian P Rubin
- Department of Anatomic Pathology, Taussig Cancer Center and the Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
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