NCCN Task Force Report: Update on the Management of Patients with Gastrointestinal Stromal Tumors

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George D. Demetri
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Margaret von Mehren
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 MD
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Cristina R. Antonescu
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Ronald P. DeMatteo
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Kristen N. Ganjoo
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Robert G. Maki
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 MD, PhD
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Peter W.T. Pisters
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Chandrajit P. Raut
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Richard F. Riedel
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Scott Schuetze
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Hema M. Sundar
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Jonathan C. Trent
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Jeffrey D. Wayne
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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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  • 1

    Nishida T, Hirota S. Biological and clinical review of stromal tumors in the gastrointestinal tract. Histol Histopathol 2000;15:12931301.

  • 2

    Thomas RM, Sobin LH. Gastrointestinal cancer. Cancer 1995;75:154170.

  • 3

    Tran T, Davila JA, El-Serag HB. The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol 2005;100:162168.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Tryggvason G, Gislason HG, Magnusson MK et al.. Gastrointestinal stromal tumors in Iceland, 1990-2003: the Icelandic GIST study, a population-based incidence and pathologic risk stratification study. Int J Cancer 2005;117:289293.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Goettsch WG, Bos SD, Breekveldt-Postma N et al.. Incidence of gastrointestinal stromal tumors is underestimated: results of a nation-wide study. Eur J Cancer 2005;41:28682872.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Rubio J, Marcos-Gragera R, Ortiz MR et al.. Population-based incidence and survival of gastrointestinal stromal tumors (GIST) in Girona, Spain. Eur J Cancer 2007;43:144148.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Nilsson B, Bumming P, Meis-Kindblom JM et al.. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era—a population-based study in western Sweden. Cancer 2005;103:821829.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Perez EA, Livingstone AS, Franceschi D et al.. Current incidence and outcomes of gastrointestinal mesenchymal tumors including gastrointestinal stromal tumors. J Am Coll Surg 2006;202:623629.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Steigen SE, Eide TJ. Trends in the incidence and survival of mesenchymal neoplasm of the digestive tract within a defined population of northern Norway. APMIS 2006;114:192200.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Agaimy A, Wunsch PH, Hofstaedter F et al.. Minute gastric sclerosing stromal tumors (GIST tumorlets) are common in adults and frequently show c-KIT mutations. Am J Surg Pathol 2007;31:113120.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol 2005;29:5268.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Miettinen M, Makhlouf H, Sobin LH et al.. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol 2006;30:477489.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 2006;23:7083.

  • 14

    Miettinen M, Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med 2006;130:14661478.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Reith JD, Goldblum JR, Lyles RH, Weiss SW. Extragastrointestinal (soft tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome. Mod Pathol 2000;13:577585.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    DeMatteo RP, Lewis JJ, Leung D et al.. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 2000;231:5158.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    van der Zwan SM, DeMatteo RP. Gastrointestinal stromal tumor: 5 years later. Cancer 2005;104:17811788.

  • 18

    Sepe PS, Brugge WR. A guide for the diagnosis and management of gastrointestinal stromal cell tumors. Nat Rev Gastroenterol Hepatol 2009;6:363371.

  • 19

    Fletcher CD, Berman JJ, Corless C et al.. Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol 2002;33:459465.

  • 20

    Chirieac LR, Trent JC, Steinert DM et al.. Correlation of immunophenotype with PFS in patients with gastrointestinal stromal tumors treated with imatinib mesylate. Cancer 2006;107:22372244.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Miettinen M, Lasota J. KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol 2005;13:205220.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Miettinen M, Sobin LH, Sarlomo-Rikala M. Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT). Mod Pathol 2000;13:11341142.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Debiec-Rychter M, Wasag B, Stul M et al.. Gastrointestinal stromal tumours (GISTs) negative for KIT (CD117 antigen) immunoreactivity. J Pathol 2004;202:430438.

  • 24

    Medeiros F, Corless CL, Duensing A et al.. KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol 2004;28:889894.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Heinrich MC, Corless CL, Duensing A et al.. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 2003;299:708710.

  • 26

    Hirota S, Ohashi A, Nishida T et al.. Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology 2003;125:660667.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Corless CL, Schroeder A, Griffith D et al.. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 2005;23:53575364.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Rossi G, Valli R, Bertolini F et al.. PDGFR expression in differential diagnosis between KIT-negative gastrointestinal stromal tumours and other primary soft-tissue tumours of the gastrointestinal tract. Histopathology 2005;46:522531.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Miselli F, Millefanti C, Conca E et al.. PDGFRA immunostaining can help in the diagnosis of gastrointestinal stromal tumors. Am J Surg Pathol 2008;32:738743.

  • 30

    Peterson MR, Piao Z, Weidner N, Yi ES. Strong PDGFRA positivity is seen in GISTs but not in other intra-abdominal mesenchymal tumors: immunohistochemical and mutational analyses. Appl Immunohistochem Mol Morphol 2006;14:390396.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Agaram NP, Wong GC, Guo T et al.. Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors. Genes Chromosomes Cancer 2008;47:853859.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Duensing A, Joseph NE, Medeiros F et al.. Protein kinase C theta (PKCtheta) expression and constitutive activation in gastrointestinal stromal tumors (GISTs). Cancer Res 2004;64:51275131.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Kim KM, Kang DW, Moon WS et al.. PKCtheta expression in gastrointestinal stromal tumor. Mod Pathol 2006;19:14801486.

  • 34

    Ou Wb, Zhu Mj, Demetri GD et al.. Protein kinase C-[theta] regulates KIT expression and proliferation in gastrointestinal stromal tumors. Oncogene 2008;27:56245634.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    West RB, Corless CL, Chen X et al.. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 2004;165:107113.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Espinosa I, Lee CH, Kim MK et al.. A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors. Am J Surg Pathol 2008;32:210218.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Miettinen M, Wang ZF, Lasota J. DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors: a study of 1840 cases. Am J Surg Pathol 2009;33:14011408.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Liegl B, Hornick JL, Corless CL, Fletcher CD. Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes. Am J Surg Pathol 2009;33:437446.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Nielsen TO, West RB, Linn SC et al.. Molecular characterisation of soft tissue tumours: a gene expression study. Lancet 2002;359:13011307.

  • 40

    Antonescu CR, Viale A, Sarran L et al.. Gene expression in gastrointestinal stromal tumors is distinguished by KIT genotype and anatomic site. Clin Cancer Res 2004;10:32823290.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Segal NH, Pavlidis P, Antonescu CR et al.. Classification and subtype prediction of adult soft tissue sarcoma by functional genomics. Am J Pathol 2003;163:691700.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Subramanian S, West RB, Corless CL et al.. Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles. Oncogene 2004;23:77807790.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Pantaleo MA, Astolfi A, Di Battista M et al.. Insulin-like growth factor 1 receptor expression in wild-type GISTs: a potential novel therapeutic target. Int J Cancer 2009;125:29912994.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44

    Agaram NP, Laquaglia MP, Ustun B et al.. Molecular characterization of pediatric gastrointestinal stromal tumors. Clin Cancer Res 2008;14:32043215.

  • 45

    Agaram NP, Besmer P, Wong GC et al.. Pathologic and molecular heterogeneity in imatinib-stable or imatinib-responsive gastrointestinal stromal tumors. Clin Cancer Res 2007;13:170181.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46

    Miettinen M, Lasota J. Gastrointestinal stromal tumors—definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 2001;438:112.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47

    Dematteo RP, Gold JS, Saran L et al.. Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer 2008;112:608615.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48

    Gold JS, Gonen M, Gutierrez A et al.. Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour: a retrospective analysis. Lancet Oncol 2009;10:10451052.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49

    Seidal T, Edvardsson H. Expression of c-kit (CD117) and Ki67 provides information about the possible cell of origin and clinical course of gastrointestinal stromal tumours. Histopathology 1999;34:416424.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50

    Saponara M, Di Battista M, Lolli C et al.. Evaluation of Ki-67 in gastrointestinal stromal tumor (GIST) [abstract]. J Clin Oncol 2009;27(Suppl 1):Abstract e21510.

  • 51

    Lasota J, Miettinen M. Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours. Histopathology 2008;53:245266.

  • 52

    Lasota J, Corless CL, Heinrich MC et al.. Clinicopathologic profile of gastrointestinal stromal tumors (GISTs) with primary KIT exon 13 or exon 17 mutations: a multicenter study on 54 cases. Mod Pathol 2008;21:476484.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53

    McAuliffe JC, Wang WL, Pavan GM et al.. Unlucky number 13? Differential effects of KIT exon 13 mutation in gastrointestinal stromal tumors. Mol Oncol 2008;2:161163.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54

    Tarn C, Rink L, Merkel E et al.. Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors. Proc Natl Acad Sci U S A 2008;105:83878392.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55

    Belinsky MG, Rink L, Cai KQ et al.. The insulin-like growth factor system as a potential therapeutic target in gastrointestinal stromal tumors. Cell Cycle 2008;7:29492955.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56

    Braconi C, Bracci R, Bearzi I et al.. Insulin-like growth factor (IGF) 1 and 2 help to predict disease outcome in GIST patients. Ann Oncol 2008;19:12931298.

  • 57

    Singer S, Rubin BP, Lux ML et al.. Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors. J Clin Oncol 2002;20:38983905.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58

    Kim TW, Lee H, Kang YK et al.. Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors. Clin Cancer Res 2004;10:30763081.

  • 59

    Andersson J, Bumming P, Meis-Kindblom JM et al.. Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis. Gastroenterology 2006;130:15731581.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 60

    Rubin BP, Singer S, Tsao C et al.. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 2001;61:81188121.

  • 61

    Corless CL, McGreevey L, Haley A et al.. KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size. Am J Pathol 2002;160:15671572.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 62

    Lasota J, Dansonka-Mieszkowska A, Stachura T et al.. Gastrointestinal stromal tumors with internal tandem duplications in 3’ end of KIT juxtamembrane domain occur predominantly in stomach and generally seem to have a favorable course. Mod Pathol 2003;16:12571264.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 63

    Martin J, Poveda A, Llombart-Bosch A et al.. Deletions affecting codons 557-558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS). J Clin Oncol 2005;23:61906198.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 64

    Antonescu CR, Sommer G, Sarran L et al.. Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors. Clin Cancer Res 2003;9:33293337.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 65

    Lasota J, Dansonka-Mieszkowska A, Sobin LH et al.. A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest 2004;84:874883.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 66

    Lasota J, Stachura J, Miettinen M. GISTs with PDGFRA exon 14 mutations represent subset of clinically favorable gastric tumors with epithelioid morphology. Lab Invest 2006;86:94100.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 67

    Heinrich MC, Corless CL, Demetri GD et al.. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003;21:43424349.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 68

    Debiec-Rychter M, Dumez H, Judson I et al.. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2004;40:689695.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 69

    Debiec-Rychter M, Sciot R, Le Cesne A et al.. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 2006;42:10931103.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 70

    Heinrich MC, Owzar K, Corless CL et al.. Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol 2008;26:53605367.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 71

    Gastrointestinal Stromal Tumor Meta-Analysis Group. Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1640 patients. J Clin Oncol 2010;28:12471253.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 72

    Heinrich MC, Maki RG, Corless CL et al.. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol 2008;26:53525359.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 73

    Blanke CD, Corless CL. State-of-the art therapy for gastrointestinal stromal tumors. Cancer Invest 2005;23:274280.

  • 74

    Ryan DP, Puchalski T, Supko JG et al.. A phase II and pharmacokinetic study of ecteinascidin 743 in patients with gastrointestinal stromal tumors. Oncologist 2002;7:531538.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 75

    Edmonson JH, Marks RS, Buckner JC, Mahoney MR. Contrast of response to dacarbazine, mitomycin, doxorubicin, and cisplatin (DMAP) plus GM-CSF between patients with advanced malignant gastrointestinal stromal tumors and patients with other advanced leiomyosarcomas. Cancer Invest 2002;20:605612.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 76

    Trent JC, Beach J, Burgess MA et al.. A two-arm phase II study of temozolomide in patients with advanced gastrointestinal stromal tumors and other soft tissue sarcomas. Cancer 2003;98:26932699.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 77

    Demetri GD, von Mehren M, Blanke CD et al.. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347:472480.

  • 78

    Heinrich MC, Griffith DJ, Druker BJ et al.. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 2000;96:925932.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 79

    Buchdunger E, Cioffi CL, Law N et al.. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 2000;295:139145.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 80

    Tuveson DA, Willis NA, Jacks T et al.. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene 2001;20:50545058.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 81

    Druker BJ, Tamura S, Buchdunger E et al.. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 1996;2:561566.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 82

    Joensuu H, Roberts PJ, Sarlomo-Rikala M et al.. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 2001;344:10521056.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 83

    Dagher R, Cohen M, Williams G et al.. Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clin Cancer Res 2002;8:30343038.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 84

    Blanke CD, Demetri GD, von Mehren M et al.. Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol 2008;26:620625.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 85

    van Oosterom AT, Judson I, Verweij J et al.. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet 2001;358:14211423.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 86

    Verweij J, van Oosterom A, Blay JY et al.. Imatinib mesylate (STI571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study. Eur J Cancer 2003;39:20062011.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 87

    Blanke CD, Rankin C, Demetri GD et al.. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol 2008;26:626632.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 88

    Verweij J, Casali PG, Zalcberg J et al.. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004;364:11271134.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 89

    Zalcberg JR, Verweij J, Casali PG et al.. Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. Eur J Cancer 2005;41:17511757.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 90

    Widmer N, Decosterd LA, Leyvraz S et al.. Relationship of imatinib-free plasma levels and target genotype with efficacy and tolerability. Br J Cancer 2008;98:16331640.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 91

    Delbaldo C, Chatelut E, Re M et al.. Pharmacokinetic-pharmacodynamic relationships of imatinib and its main metabolite in patients with advanced gastrointestinal stromal tumors. Clin Cancer Res 2006;12:60736078.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 92

    Demetri GD, Wang Y, Wehrle E et al.. Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors. J Clin Oncol 2009;27:31413147.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 93

    Guilhot F. Indications for imatinib mesylate therapy and clinical management. Oncologist 2004;9:271281.

  • 94

    Ferrero D, Pogliani EM, Rege-Cambrin G et al.. Corticosteroids can reverse severe imatinib-induced hepatotoxicity. Haematologica 2006;91:ECR27.

  • 95

    Ganjoo KN, Demetri GD, Jacobs C, Patel S. Acute myeloid leukemia in patients with gastrointestinal stromal tumors treated with Gleevec. Leuk Lymphoma 2009;50:18821884.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 96

    Berman E, Nicolaides M, Maki RG et al.. Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med 2006;354:20062013.

  • 97

    Joensuu H, Reichardt P. Imatinib and altered bone and mineral metabolism [letter]. N Eng J Med 2006;355;627628.

  • 98

    Kerkela R, Grazette L, Yacobi R et al.. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nature Med 2006;12:881882.

  • 99

    Trent JC, Patel SS, Zhang J et al.. Rare incidence of congestive heart failure in gastrointestinal stromal tumor and other sarcoma patients receiving imatinib mesylate. Cancer 2009;116:184192.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 100

    Quek R, Morgan JA, George S et al.. Small molecule tyrosine kinase inhibitor and depression. J Clin Oncol 2009;27:312313.

  • 101

    Benjamin RS, Debiec-Rychter M, Le Cesne A et al.. Gastrointestinal stromal tumors II: medical oncology and tumor response assessment. Semin Oncol 2009;36:302311.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 102

    Maleddu A, Pantaleo MA, Nannini M et al.. Mechanisms of secondary resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumours (review). Oncol Rep 2009;21:13591366.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 103

    Chen LL, Trent JC, Wu EF et al.. A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res 2004;64:59135919.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 104

    Antonescu CR, Besmer P, Guo T et al.. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 2005;11:41824190.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 105

    Debiec-Rychter M, Cools J, Dumez H et al.. Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology 2005;128:270279.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 106

    Heinrich MC, Corless CL, Blanke CD et al.. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol 2006;24:47644774.

  • 107

    Wardelmann E, Merkelbach-Bruse S, Pauls K et al.. Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res 2006;12:17431749.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 108

    Liegl B, Kepten I, Le C et al.. Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol 2008;216:6474.

  • 109

    Burger H, Nooter K. Pharmacokinetic resistance to imatinib mesylate: role of the ABC drug pumps ABCG2 (BCRP) and ABCB1 (MDR1) in the oral bioavailability of imatinib. Cell Cycle 2004;3:15021505.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 110

    Burger H, van Tol H, Brok M et al.. Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther 2005;4:747752.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 111

    Demetri GD, van Oosterom AT, Garrett CR et al.. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006;368:13291338.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 112

    Demetri GD, Huang X, Garrett CR et al.. Novel statistical analysis of long-term survival to account for crossover in a phase III trial of sunitinib (SU) vs. placebo (PL) in advanced GIST after imatinib (IM) failure [abstract]. J Clin Oncol 2008;26(Suppl 1):Abstract 10524.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 113

    George S, Blay JY, Casali PG et al.. Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. Eur J Cancer 2009;45:19591968.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 114

    Izzedine H, Ederhy S, Goldwasser F et al.. Management of hypertension in angiogenesis inhibitor-treated patients. Ann Oncol 2009;20:807815.

  • 115

    Zhu X, Stergiopoulos K, Wu S. Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. Acta Oncol 2009;48:917.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 116

    Azizi M, Chedid A, Oudard S. Home blood-pressure monitoring in patients receiving sunitinib. N Engl J Med 2008;358:9597.

  • 117

    Chu TF, Rupnick MA, Kerkela R et al.. Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib. Lancet 2007;370:20112019.

  • 118

    Bello CL, Mulay M, Huang X et al.. Electrocardiographic characterization of the QTc interval in patients with advanced solid tumors: pharmacokinetic-pharmacodynamic evaluation of sunitinib. Clin Cancer Res 2009;15:70457052.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 119

    Torino F, Corsello SM, Longo R et al.. Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy. Nat Rev Clin Oncol 2009;6:219228.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 120

    Desai J, Yassa L, Marqusee E et al.. Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med 2006;145:660664.

  • 121

    Chu D, Lacouture ME, Weiner E, Wu S. Risk of hand-foot skin reaction with the multitargeted kinase inhibitor sunitinib in patients with renal cell and non-renal cell carcinoma: a meta-analysis. Clin Genitourin Cancer 2009;7:1119.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 122

    Gajiwala KS, Wu JC, Christensen J et al.. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc Natl Acad Sci U S A 2009;106:15421547.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 123

    Guo T, Hajdu M, Agaram NP et al.. Mechanisms of sunitinib resistance in gastrointestinal stromal tumors harboring KITAY502-3ins mutation: an in vitro mutagenesis screen for drug resistance. Clin Cancer Res 2009;15:68626870.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 124

    Kao J, Packer S, Vu HL et al.. Phase I study of concurrent sunitinib and image-guided radiotherapy followed by maintenance sunitinib for patients with oligometastases: acute toxicity and preliminary response. Cancer 2009;115:35713580.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 125

    Wiebe L, Kasza KE, Maki RG et al.. Activity of sorafenib (SOR) in patients (pts) with imatinib (IM) and sunitinib (SU)-resistant (RES) gastrointestinal stromal tumors (GIST): a phase II trial of the University of Chicago Phase II Consortium [abstract]. J Clin Oncol 2008;26(Suppl 1):Abstract 10502.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 126

    Reichardt P, Montemurro M, Gelderblom H et al.. Sorafenib fourth-line treatment in imatinib-, sunitinib-, and nilotinib-resistant metastatic GIST: a retrospective analysis [abstract]. J Clin Oncol 2009;27(Suppl 1):Abstract 10564.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 127

    Dewaele B, Wasag B, Cools J et al.. Activity of dasatinib, a dual SRC/ABL kinase inhibitor, and IPI-504, a heat shock protein 90 inhibitor, against gastrointestinal stromal tumor–associated PDGFRAD842V mutation. Clin Cancer Res 2008;14:57495758.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 128

    Schittenhelm MM, Shiraga S, Schroeder A et al.. Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res 2006;66:473481.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 129

    Demetri GD, Lo Russo P, MacPherson IR et al.. Phase I dose-escalation and pharmacokinetic study of dasatinib in patients with advanced solid tumors. Clin Cancer Res 2009;15:62326240.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 130

    Demetri GD, Casali PG, Blay JY et al.. A phase I study of single-agent nilotinib or in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res 2009;15:59105916.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 131

    Montemurro M, Schoffski P, Reichardt P et al.. Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib. Eur J Cancer 2009;45:22932297.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 132

    Blay JY, Le Cesne A, Ray-Coquard I et al.. Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol 2007;25:11071113.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 133

    Fumagalli E, Coco P, Morosi C et al.. Rechallenge with imatinib in GIST patients resistant to second or third line therapy [abstract]. Presented at the 15th Annual CTOS Meeting; November 5–7, 2009; Miami Beach, Florida. Abstract 39404.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 134

    Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005;353:487497.

  • 135

    Noens L, van Lierde MA, De Bock R et al.. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood 2009;113:54015411.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 136

    Duffaud F, Ray-Coquard I, Bui B et al.. Time to secondary resistance (TSR) after interruption of imatinib: updated results of the prospective French Sarcoma Group randomized phase III trial on long-term survival [abstract]. J Clin Oncol 2009;27(Suppl 1):Abstract 10508.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 137

    Fong Y, Coit DG, Woodruff JM et al.. Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients. Ann Surg 1993;217:7277.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 138

    Ng EH, Pollock RE, Munsell MF et al.. Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging. Ann Surg 1992;215:6877.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 139

    Akwari OE, Dozois RR, Weiland LH et al.. Leiomyosarcoma of the small and large bowel. Cancer 1978;42:13751384.

  • 140

    McGrath PC, Neifeld JP, Lawrence WJ et al.. Gastrointestinal sarcomas. Analysis of prognostic factors. Ann Surg 1987;206:706710.

  • 141

    Kawanowa K, Sakuma Y, Sakurai S et al.. High incidence of microscopic gastrointestinal stromal tumors in the stomach. Hum Pathol 2006;37:15271535.

  • 142

    Agaimy A, Wunsch PH, Dirnhofer S et al.. Microscopic gastrointestinal stromal tumors in esophageal and intestinal surgical resection specimens: a clinicopathologic, immunohistochemical, and molecular study of 19 lesions. Am J Surg Pathol 2008;32:867873.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 143

    Chetty R. Small and microscopically detected gastrointestinal stromal tumours: an overview. Pathology 2008;40:912.

  • 144

    Davila RE, Faigel DO. GI stromal tumors. Gastrointest Endosc 2003;58:8088.

  • 145

    Lok KH, Lai L, Yiu HL et al.. Endosonographic surveillance of small gastrointestinal tumors originating from muscularis propria. J Gastrointestin Liver Dis 2009;18:177180.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 146

    Sun S, Ge N, Wang C et al.. Endoscopic band ligation of small gastric stromal tumors and follow-up by endoscopic ultrasonography. Surg Endosc 2007;21:574578.

  • 147

    Otani Y, Kitajima M. Laparoscopic surgery: too soon to decide. Gastric Cancer 2005;8:135136.

  • 148

    Novitsky YW, Kercher KW, Sing RF et al.. Long-term outcomes of laparoscopic resection of gastric gastrointestinal stromal tumors. Ann Surg 2006;243:738745; discussion 745–747.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 149

    Otani Y, Furukawa T, Yoshida M et al.. Operative indications for relatively small (2-5 cm) gastrointestinal stromal tumor of the stomach based on analysis of 60 operated cases. Surgery 2006;139:484492.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 150

    Nakamori M, Iwahashi M, Nakamura M et al.. Laparoscopic resection for gastrointestinal stromal tumors of the stomach. Am J Surg 2008;196:425429.

  • 151

    Nishimura J, Nakajima K, Omori T et al.. Surgical strategy for gastric gastrointestinal stromal tumors: laparoscopic vs. open resection. Surg Endosc 2007;21:875878.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 152

    Huguet KL, Rush RM Jr, Tessier DJ et al.. Laparoscopic gastric gastrointestinal stromal tumor resection: the mayo clinic experience. Arch Surg 2008;143:587590.

  • 153

    Eisenberg BL, Harris J, Blanke CD et al.. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol 2009;99:4247.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 154

    McAuliffe JC, Hunt KK, Lazar AJ et al.. A randomized, phase II study of preoperative plus postoperative imatinib in GIST: evidence of rapid radiographic response and temporal induction of tumor cell apoptosis. Ann Surg Oncol 2009;16:910919.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 155

    Bonvalot S, Eldweny H, Pechoux CL et al.. Impact of surgery on advanced gastrointestinal stromal tumors (GIST) in the imatinib era. Ann Surg Oncol 2006;13:15961603.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 156

    Hohenberger P, Oladeji O, Licht T et al.. Neoadjuvant imatinib and organ preservation in locally advanced gastrointestinal stromal tumors (GIST) [abstract]. J Clin Oncol 2009;27(Suppl 1):Abstract 10550.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 157

    DeMatteo RP, Owzar K, Antonescu CR et al.. Efficacy of adjuvant imatinib mesylate following complete resection of localized, primary gastrointestinal stromal tumor (GIST) at high risk of recurrence: the U.S. Intergroup phase II trial ACOSOG Z9000 [abstract]. Preseneted at the 2008 ASCO Gastrointestinal Cancers Symposium; January 25–27, 2008; Orlando, Florida. Abstract 8.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 158

    DeMatteo R, Owzar K, Maki R et al.. Adjuvant imatinib mesylate increases recurrence free survival (RFS) in patients with completely resected localized primary gastrointestinal stromal tumor (GIST): North American Intergroup Phase III trial ACOSOG Z9001 [abstract]. Presented at the 43rd ASCO Annual Meeting; June 1–5, 2007; Chicago, Illinois. Abstract 10079.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 159

    Dematteo RP, Ballman KV, Antonescu CR et al.. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, doubleblind, placebocontrolled trial. Lancet 2009;373:10971104.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 160

    Zhan WH, China Gastrointestinal Cooperative Group. Efficacy and safety of adjuvant post-surgical therapy with imatinib in patients with high risk of relapsing GIST [abstract]. J Clin Oncol 2007;25(Suppl 1):Abstract 10045.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 161

    Li J, Gong FJ, Wu WA, Shen L. Adjuvant therapy with imatinib in gastrointestinal stromal tumor (GIST) patients with intermediate or high risk: analysis from a single-center contrast study [abstract]. J Clin Oncol 2009;27(Suppl 1):Abstract 10556.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 162

    Scaife CL, Hunt KK, Patel SR et al.. Is there a role for surgery in patients with “unresectable” cKIT+ gastrointestinal stromal tumors treated with imatinib mesylate? Am J Surg 2003;186:665669.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 163

    Bumming P, Andersson J, Meis-Kindblom JM et al.. Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients. Br J Cancer 2003;89:460464.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 164

    Bauer S, Hartmann JT, de Wit M et al.. Resection of residual disease in patients with metastatic gastrointestinal stromal tumors responding to treatment with imatinib. Int J Cancer 2005;117:316325.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 165

    Raut CP, Posner M, Desai J et al.. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol 2006;24:23252331.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 166

    Rutkowski P, Nowecki Z, Nyckowski P et al.. Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate. J Surg Oncol 2006;93:304311.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 167

    Andtbacka RH, Ng CS, Scaife CL et al.. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol 2007;14:1424.

  • 168

    Gronchi A, Fiore M, Miselli F et al.. Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg 2007;245:341346.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 169

    DeMatteo RP, Maki RG, Singer S et al.. Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor (GIST). Ann Surg 2007;245:347352.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 170

    Sym SJ, Ryu MH, Lee JL et al.. Surgical intervention following imatinib treatment in patients with advanced gastrointestinal stromal tumors (GISTs). J Surg Oncol 2008;98:2733.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 171

    Mussi C, Ronellenfitsch U, Jakob J et al.. Post-imatinib surgery in advanced/metastatic GIST: is it worthwhile in all patients? Ann Oncol 2010;21:403408.

  • 172

    Raut CP, Wang Q, Manola J et al.. Cytoreductive surgery in patients with metastatic gastrointestinal stromal tumor treated with sunitinib malate. Ann Surg Oncol 2010;17:407415.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 173

    Ye YJ, Gao ZD, Poston GJ, Wang S. Diagnosis and multi-disciplinary management of hepatic metastases from gastrointestinal stromal tumour (GIST). Eur J Surg Oncol 2009;35:787792.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 174

    Maluccio MA, Covey AM, Schubert J et al.. Treatment of metastatic sarcoma to the liver with bland embolization. Cancer 2006;107:16171623.

  • 175

    Kobayashi K, Gupta S, Trent JC et al.. Hepatic artery chemoembolization for 110 gastrointestinal stromal tumors: response, survival, and prognostic factors. Cancer 2006;107:28332841.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 176

    Avritscher R, Gupta S. Gastrointestinal stromal tumor: role of interventional radiology in diagnosis and treatment. Hematol Oncol Clin North Am 2009;23:129137.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 177

    Pawlik TM, Vauthey JN, Abdalla EK et al.. Results of a single-center experience with resection and ablation for sarcoma metastatic to the liver. Arch Surg 2006;141:537543; discussion 543–534.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 178

    Serralta AS, Sanjuan FR, Moya AH et al.. Combined liver transplantation plus imatinib for unresectable metastases of gastrointestinal stromal tumours. Eur J Gastroenterol Hepatol 2004;16:12371239.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 179

    Benjamin RS, Choi H, Macapinlac HA et al.. We should desist using RECIST, at least in GIST. J Clin Oncol 2007;25:17601764.

  • 180

    Le Cesne A, Van Glabbeke M, Verweij J et al.. Absence of progression as assessed by response evaluation criteria in solid tumors predicts survival in advanced GI stromal tumors rreated with imatinib mesylate: the Intergroup EORTC-ISG-AGITG phase III trial. J Clin Oncol 2009;27:39693974.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 181

    Holdsworth CH, Badawi RD, Manola JB et al.. CT and PET: early prognostic indicators of response to imatinib mesylate in patients with gastrointestinal stromal tumor. AJR Am J Roentgenol 2007;189:W324330.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 182

    Choi H. Critical issues in response evaluation on computed tomography: lessons from the gastrointestinal stromal tumor model. Curr Oncol Rep 2005;7:307311.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 183

    Choi H, Charnsangavej C, Faria SC et al.. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 2007;25:17531759.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 184

    Shankar S, vanSonnenberg E, Desai J et al.. Gastrointestinal stromal tumor: new nodule-within-a-mass pattern of recurrence after partial response to imatinib mesylate. Radiology 2005;235:892898.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 185

    Van den Abbeele AD, Badawi RD. Use of positron emission tomography in oncology and its potential role to assess response to imatinib mesylate therapy in gastrointestinal stromal tumors (GISTs). Eur J Cancer 2002;38(Suppl 5):S6065.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 186

    Van den Abbeele AD, Badawi RD, Cliche JP et al.. FDG-PET as a surrogate marker for the response to Gleevec (imatinib mesylate) in patients with advanced gastrointestinal stromal tumors (GIST). J Nucl Med 2003;44:24P25P.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 187

    Young H, Baum R, Cremerius U et al.. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer 1999;35:17731782.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 188

    Van Den Abbeele AD, Badawi RD, Manola J et al.. Effects of cessation of imatinib mesylate (IM) therapy in patients (pts) with IMrefractory gastrointestinal stromal tumors (GIST) as visualized by FDGPET scanning [abstract]. J Clin Oncol 2004;22(Suppl 1):Abstract 3012.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 189

    Prior JO, Montemurro M, Orcurto MV et al.. Early prediction of response to sunitinib after imatinib failure by 18F-fluorodeoxyglucose positron emission tomography in patients with gastrointestinal stromal tumor. J Clin Oncol 2009;27:439445.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 190

    Miettinen M, Lasota J, Sobin LH. Gastrointestinal stromal tumors of the stomach in children and young adults. Am J Surg Pathol 2005;29:13731381.

  • 191

    Prakash S, Sarran L, Socci N et al.. Gastrointestinal stromal tumors in children and young adults. J Pediatr Hematol Oncol 2005;27:179187.

  • 192

    Janeway KA, Liegl B, Harlow A et al.. Pediatric KIT wild-type and platelet-derived growth factor receptor alpha-wild-type gastrointestinal stromal tumors share KIT activation but not mechanisms of genetic progression with adult gastrointestinal stromal tumors. Cancer Res 2007;67:90849088.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 193

    Janeway KA, Albritton KH, Van Den Abbeele AD et al.. Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib. Pediatr Blood Cancer 2009;52:767771.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 194

    Stratakis CA, Carney JA. The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications. J Intern Med 2009;266:4352.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 195

    Kleinbaum EP, Lazar AJ, Tamborini E et al.. Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor. Int J Cancer 2008;122:711718.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 196

    Agarwal R, Robson M. Inherited predisposition to gastrointestinal stromal tumor. Hematol Oncol Clin North Am 2009;23:113.

  • 197

    Antonescu CR. Gastrointestinal stromal tumor (GIST) pathogenesis, familial GIST, and animal models. Semin Diagn Pathol 2006;23:6369.

  • 198

    Pasini B, McWhinney SR, Bei T et al.. Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur J Hum Genet 2008;16:7988.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 199

    Hao HX, Khalimonchuk O, Schraders M et al.. SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science 2009;325:11391142.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 200

    Mussi C, Schildhaus HU, Gronchi A et al.. Therapeutic consequences from molecular biology for gastrointestinal stromal tumor patients affected by neurofibromatosis type 1. Clin Cancer Res 2008;14:45504555.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 201

    Shinomura Y, Kinoshita K, Tsutsui S, Hirota S. Pathophysiology, diagnosis, and treatment of gastrointestinal stromal tumors. J Gastroenterol 2005;40:775780.

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