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Imaging Tumor Response to Therapy pp 41–60Cite as

Gastrointestinal Stromal Tumors

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Abstract

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. According to tumor size, GIST incidence varies from a highly prevalent tumor the “micro-GIST,” which is < 2 cm wide [1] and is estimated to occur in up to 22% of the general population, to a rare disease characterized by a tumor > 2 cm and with an annual incidence of about 15/1,000,000 [2]. While the clinical relevance of microGIST is still under evaluation, at this point it is considered to be minimal. GISTs may develop from the esophagus to the rectum and are most common in the stomach (60–70% of the cases) followed by the small intestine (30%), and lastly by the rectum (< 10%) [3]. Although no GIST > 2 cm can be considered benign, the risk of local relapse and metastasis varies according to tumor size and site of origin, and the number of mitoses evaluated on 50 microscopic high-power fields. This risk stratification proposed by Miettinen and Lasota [3] is widely used as a prognosticator after complete surgery, which is still the mainstay of therapy. However, despite complete surgical removal of the tumor, the 50% relapse rate is surprisingly consistent throughout different large series [4]. Relapse may occur locally but mostly involves the peritoneum and liver. Patients with relapse not amenable to surgery previously died within 12 months [5] due to the chemoresistance of GIST, in which the response rate to chemotherapy is < 5% [6].

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References

  1. Agaimy A, Wünsch PH, Hofstaedter F et al (2007) Minute gastric sclerosing stromal tumors (GIST tumorlets) are common in adults and frequently show c-KIT mutations. Am J Surg Pathol 31:113–120

    Article  PubMed  Google Scholar 

  2. Nilsson B, Bumming P, Meis-Kindblom JM et al (2005) Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the pre-imatinib mesylate eraa population-based study in western Sweden. Cancer 103:821–829

    Article  PubMed  Google Scholar 

  3. Miettinen M, Lasota J (2006) Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 23:70–78

    Article  PubMed  Google Scholar 

  4. Gold JS, Gonen M, Gutierrez A et al (2009) Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localized primary gastrointestinal stromal tumor: a retrospective analysis. Lancet Oncol 10:1045–1052

    Article  PubMed  Google Scholar 

  5. Plaat BE, Hollema H, Molenaar WM et al (2000) Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins. J Clin Oncol 18:3211–3220

    PubMed  CAS  Google Scholar 

  6. de Pas T, Casali PG, Toma S et al; Italian Sarcoma Group (2003) Gastrointestinal stromal tumors: should they be treated with the same systemic chemotherapy as other soft tissue sarcomas? Oncology 64:186–188

    Article  PubMed  Google Scholar 

  7. Hirota S, Isozaki K, Moriyama Y et al (1998) Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279:577–580

    Article  PubMed  CAS  Google Scholar 

  8. Heinrich MC, Corless CL, Duensing A et al (2003) PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299:708–710

    Article  PubMed  CAS  Google Scholar 

  9. Joensuu H, Roberts PJ, Sarlomo-Rikala M et al (2001) Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344:1052–1056

    Article  PubMed  CAS  Google Scholar 

  10. Verweij J, Casali PG, Zalcberg J et al (2004) Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 364:1127–1134

    Article  PubMed  CAS  Google Scholar 

  11. Blanke CD, Rankin C, Demetri GD et al (2008) 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 26:626–632

    Article  PubMed  CAS  Google Scholar 

  12. Heinrich MC, Corless CL, Demetri GD et al (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21:4342–4349

    Article  PubMed  CAS  Google Scholar 

  13. Wang JH, Lasota J, and Miettinen M (2011) Succinate Dehydrogenase subunit B (SDHB) is expressed in neurofibromatosis 1-associated gastrointestinal stromal tumors (GISTs): implications for the SDHB expression based classification of GISTs. J Cancer 2:90–93

    Article  PubMed  CAS  Google Scholar 

  14. The NCCN soft tissue sarcoma clinical practice guidelines in oncology (version 1, 2010) (c) 2010 National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the guideline, go online to www.nccn.org 2010. http://www.nccn.org

  15. Casali PG, Blay JY; ESMO/CONTICANET/EUROBONET Consensus Panel of Experts (2010) Gastrointestinal stromal tumours: ESMO clinical practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 21Suppl 5:v98–102

    Article  Google Scholar 

  16. Hohenberger P, Ronellenfitsch U, Oladeji O et al (2010) Pattern of recurrence in patients with ruptured primary gastrointestinal stromal tumour. Br J Surg 97:1854–1859

    Article  PubMed  CAS  Google Scholar 

  17. Fiore M, Palassini E, Fumagalli E et al (2009) Preoperative imatinib mesylate for unresectable or locally advanced primary gastrointestinal stromal tumors (GIST). Eur J Surg Oncol 35:739–745

    Article  PubMed  CAS  Google Scholar 

  18. Raut CP, Posner M, Desai J et al (2006) Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol 24:2325–2331

    Article  PubMed  CAS  Google Scholar 

  19. DeMatteo RP, Maki RG, Singer S et al (2007) Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor. Ann Surg 245:347–352

    Article  PubMed  Google Scholar 

  20. Gronchi A, Fiore M, Miselli F et al (2007) Surgery of residual disease following moleculartargeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg 245:341–346

    Article  PubMed  Google Scholar 

  21. Gramza AW, Corless CL, Heinrich MC (2009) Resistance to tyrosine kinase Inhibitors in gastrointestinal stromal tumors. Clin Cancer Res 15:7510–7518

    Article  PubMed  CAS  Google Scholar 

  22. Dematteo RP, Ballman KV, Antonescu CR et al (2009) Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 373:1097–104

    Article  PubMed  CAS  Google Scholar 

  23. Joensuu H, Eriksson M, Hatrmann J et al (2011) Twelve versus 36 months of adjuvant imatinib (IM) as treatment of operable GIST with a high risk of recurrence: final results of a randomized trial (SSGXVIII/AIO). J Clin Oncol 29: (suppl; abstr LBA1) 2011 ASCO Annual Meeting

    Google Scholar 

  24. Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST) (2010) Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. J Clin Oncol 28:1247–1253

    Article  Google Scholar 

  25. Zalcberg JR, Verweij J, Casali PG et al, EORTC Soft Tissue and Bone Sarcoma Group, the Italian Sarcoma Group; Australasian Gastrointestinal Trials Group (2005) 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 41:1751–1757

    Article  PubMed  CAS  Google Scholar 

  26. Demetri GD, van Oosterom AT, Garrett CR et al (2006) Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368:1329–1338

    Article  PubMed  CAS  Google Scholar 

  27. George S, Blay JY, Casali PG et al (2009) Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. Eur J Cancer 45:1959–1968

    Article  PubMed  CAS  Google Scholar 

  28. Schittenhelm MM, Shiraga S, Schroeder A et al (2006) Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxta-membrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res 66:473–481

    Article  PubMed  CAS  Google Scholar 

  29. Wiebe L, Kasza KE, Maki RG et al (2008) 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. J Clin Oncol 26:553s

    Google Scholar 

  30. Mankoff DA et al (2007) Tumor-specific positron emission tomography imaging in patients: [18F] fluorodeoxyglucose and beyond. Clin Canc Res 13:3460–3469

    Article  CAS  Google Scholar 

  31. Stroobants S, Goeminne J, Seegers M et al (2003) 18FDG-Positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Glivec). Eur J Cancer 39:2012–2020

    Article  PubMed  CAS  Google Scholar 

  32. Shankar S, van Sonnenberg E, Desai J et al (2005) Gastrointestinal stromal tumor: new nodule-within-a-mass pattern of recurrence after partial response to imatinib mesylate. Radiology 235:892–898

    Article  PubMed  Google Scholar 

  33. Choi H, Charnsangavej C, Faria SC et al (2007) 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 25:1753–1759

    Article  PubMed  Google Scholar 

  34. Le Cesne A, Van Glabbeke M, Verweij J et al (2009) Absence of progression as assessed by response evaluation criteria in solid tumors predicts survival in advanced GI stromal tumors treated with imatinib mesylate: the intergroup EORTC-ISG-AGITG phase III trial. J Clin Oncol 27:3969–3974

    Article  PubMed  Google Scholar 

  35. Desai J (2011) Response assessment in gastrointestinal stromal tumor. Int J Cancer 128:1251–1258

    Article  PubMed  CAS  Google Scholar 

  36. Prior JO, Montemurro M, Orcurto MV et al (2009) Early prediction of response to sunitinib after imatinib failure by 18F-fluorodeoxyglucose positron emission tomography in patients with gastrointestinal stromal tumor. J Clin Oncol 27:439–445

    Article  PubMed  CAS  Google Scholar 

  37. Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52–60

    Article  PubMed  CAS  Google Scholar 

  38. Hong X, Choi H, Loyer EM et al (2006) Gastrointestinal stromal tumor: role of CT in diagnosis and surveillance after treatment with imatinib. RadioGraphics 26:481–449

    Article  PubMed  Google Scholar 

  39. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Istitute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    Article  PubMed  CAS  Google Scholar 

  40. Phongkitkarun S, Phaisanphrukkun C, Jatchavala J, Sirachainan E (2008) Assessment of gastrointestinal stromal tumors with computed tomography following treatment with imatinib mesylate. World J Gastroenterol 14:892–898

    Article  PubMed  CAS  Google Scholar 

  41. Benjamin RS, Choi H, Macapinlac HA et al (2007) We should desist using RECIST, at least in GIST. J Clin Oncol. 25:1760–1764

    Article  PubMed  Google Scholar 

  42. Bensimhon D, Soyer P, Brouland JP et al (2008) Gastrointestinal stromal tumors: role of Computed Tomography before and after treatment. Gastroenterol Clin Biol 32(1 Pt. 1):91–97

    Article  PubMed  CAS  Google Scholar 

  43. Desai J (2011) Response assessment in gastrointestinal stromal tumor. Int J Cancer 128:1251–1258

    Article  PubMed  CAS  Google Scholar 

  44. Menu Y (2007) Evaluation of tumor response to treatment with targeted therapies: standard or targeted criteria? Bull Cancer 94(7 Suppl):F231–9

    Google Scholar 

  45. Bensimhon D, Soyer P, Boudiaf M et al (2009) Imaging of gastrointestinal stromal tumors. J Radiol 90:469–480

    Article  PubMed  CAS  Google Scholar 

  46. Dudeck O, Zeile M, Reichardt P, Pink D (2011) Comparison of RECIST and Choi criteria for computed tomographic response evaluation in patients with advanced gastrointestinal stromal tumor treated with sunitinib. Ann Oncol 22:1828–1833

    Article  PubMed  CAS  Google Scholar 

  47. Mabillea, M, Vanela, D, Albiterd M et al (2009) Follow-up of hepatic and peritoneal metastases of gastrointestinal tumors (GIST) under Imatinib therapy requires different criteria of radiological evaluation (size is not everything!!!)”. European Journal of Radiology 69:204–208

    Article  Google Scholar 

  48. Antoch G, Kanja J et al (2004) Comparison of PET, CT and Dual Modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors. J Nucl Med 45:357–365

    PubMed  CAS  Google Scholar 

  49. Choi H, Charnsangave C, de Castro Faria S et al (2004) CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with FDG PET findings. AJR Am J Roentgenol 183:1619–1628

    PubMed  Google Scholar 

  50. Gayed I, Vu T, Iyer R et al (2004) The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors. J Nucl Med 45:17–21

    PubMed  CAS  Google Scholar 

  51. Holdsworth CH, Badawi RD, Manola JB et al (2007) CT and PET: early prognostic indicators of response to imatinib mesylate in patients with gastrointestinal stromal tumor. AJR Am J Roentgenol 189:W324–30

    Article  Google Scholar 

  52. Prenen H, Stefan C, Landuyt B et al (2005) Imatinib mesylate inhibits glucose uptake in gastrointestinal stromal tumor cells by downregulation of the glucose transporters recruiment to the plasma membrane. Am J Biochemi Biotechnol 1:95–102

    Article  CAS  Google Scholar 

  53. Cullinane C, Dorow DS, Kansara M et al (2005) An in vivo tumor model exploiting metabolic response as a biomarker for targeted drug development. Cancer Res 65:9633–9636

    Article  PubMed  CAS  Google Scholar 

  54. Stroobants S, Goeminne J, Seegers M et al (2003) 18FDG-Positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Glivec). Eur J Cancer 39:2012–2020

    Article  PubMed  CAS  Google Scholar 

  55. Goerres GW, Stupp R, Barghouth G et al (2005) The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate. Eur J Nucl Med Mol Imaging 32:153–162

    Article  PubMed  CAS  Google Scholar 

  56. Tang L, Zhang XP, Sun YS et al (2011) Gastrointestinal stromal tumors treated with imatinib mesylate: apparent diffusion coefficent in the evaluation of therapy response in patients. Radiology 258:729–738

    Article  PubMed  Google Scholar 

  57. Stroszczynski C, Jost D, Reichardt P et al (2005) Follow-up of gastro-intestinal stromal tumours (GIST) during treatment with imatinib mesylate by abdominal MRI. Eur Radiol 15:2448–2456

    Article  PubMed  Google Scholar 

  58. Schlemmer M, Sourbrona S, Schinwaldb N et al (2011) Perfusion patterns of metastatic gastrointestinal stromal tumor lesions under specific molecular therapy. Eur J Radiol 77:312–314

    Article  PubMed  Google Scholar 

  59. Apfaltrer P, Meyer M, Meier C et al (2012) Contrast-enhanced dual-energy CT of gastrointestinal stromal tumors is iodine-related attenuation a potential indicator of tumor response? Invest Radiol 47:65–70

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Medical Oncology, Institute for Cancer Research and Treatment (IRCC), Candiolo (Turin), Italy

    Giovanni Grignani & Paola Boccone

  2. Nuclear Medicine Unit, Institute for Cancer Research and Treatment (IRCC), Candiolo (Turin), Italy

    Teresio Varetto

  3. Division of Radiology, Mauriziano “Umberto I” Hospital, Turin, Italy

    Stefano Cirillo

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  1. Giovanni Grignani
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  2. Paola Boccone
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  3. Teresio Varetto
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  4. Stefano Cirillo
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Editors and Affiliations

  1. Department of Medical Oncology, University of Turin Institute for Cancer Research and Treatment (IRCC), Candiolo (Turin), Italy

    Massimo Aglietta

  2. Radiology Unit, Institute for Cancer Research and Treatment (IRCC), Candiolo (Turin), Italy

    Daniele Regge

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Grignani, G., Boccone, P., Varetto, T., Cirillo, S. (2012). Gastrointestinal Stromal Tumors. In: Aglietta, M., Regge, D. (eds) Imaging Tumor Response to Therapy. Springer, Milano. https://doi.org/10.1007/978-88-470-2613-1_3

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  • DOI: https://doi.org/10.1007/978-88-470-2613-1_3

  • Publisher Name: Springer, Milano

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