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Quantitative functional imaging by Dynamic Contrast Enhanced Ultrasonography (DCE-US) in GIST patients treated with masatinib

  • PHASE II STUDIES
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Summary

Objectives To determine the quantitative parameters of DCE-US for predicting early functional response of patients with metastatic gastrointestinal stromal tumors (GIST). Materials and methods Phase II multicentre clinical trial in patients with metastatic GIST treated with masatinib mesylate (7.5 mg/kg daily by oral route) Patients followed using three different imaging techniques: 1) DCE-US before treatment and on days 1, 7, 15 and after 1, 2, 4, 6 months and every 3 months. 2) CT assessments, using RECIST criteria, before treatment, after 2, 4, 6 months and then every 3 months. 3) FDG PET before treatment and after 1 month. Results Twenty patients included and followed-up for up to 36 months, with 269 DCE-US examinations performed. No significant changes in the 7 selected DCE-US variables on day 1 and 7 vs baseline. On day 15, significant reductions in all the variables related to blood volume recorded: area under the curve (AUC) (p = 0. 004), area under the wash-in (AUWI) (p = 0.002), area under the wash-out (AUWO) (p = 0.002) and Peak Intensity (p = 0.005). Also slope of wash-in changed significantly (p = 0.003). An important reduction in Standard Uptake Values (SUV) recorded in 7/11 patients (PFS >18 months). Decrease in DCE-US AUC, AUWI and AUWO values on day 7 were predictive of PET-CT results. Conclusions AUC AUWI, AUWO are the DCE-US parameters related to blood volume that at D 15 can predict the response of GISTs to treatment with masatinib. Additional studies are ongoing.

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References

  1. Connolly EM, Gaffney E, Reynolds JV (2003) Gastrointestinal stromal tumours. Br J Surg 90:1178–1186. doi:10.1002/bjs.4352

    Article  PubMed  CAS  Google Scholar 

  2. Sarlomo-Rikala M, Kovatich AJ, Barusevicius A, Miettinen M (1998) CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol 11:728–734

    PubMed  CAS  Google Scholar 

  3. Bono P, Krause A, Von Mehren M et al (2004) Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib. Blood 103:2929–2935. doi:10.1182/blood-2003-10-3443

    Article  PubMed  CAS  Google Scholar 

  4. Rubin BP, Singer S, Tsao C et al (2001) KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 61:8118–8121

    PubMed  CAS  Google Scholar 

  5. Zhu J, Wang Y, Hou M, Li HY, Zhang J (2007) Imatinib mesylate treatment for advanced gastrointestinal stromal tumor: a pilot study focusing on patients experiencing sole liver metastasis after a prior radical resection. Oncology 73:324–327. doi:10.1159/000134475

    Article  PubMed  CAS  Google Scholar 

  6. Joensuu H, De Braud F, Coco P et al (2008) Phase II open-label study of PTK787/ZK222684 for the treatment of metastatic gastrointestinal stromal tumors resistant to imatinib mesylate. Ann Oncol 19:173–177. doi:10.1093/annonc/mdm419

    Article  PubMed  CAS  Google Scholar 

  7. Nishida T, Shirao K, Sawaki A et al (2008) Efficacy and safety profile of imatinib mesylate (ST1571) in Japanese patients with advanced gastrointestinal stromal tumors: a phase II study (STi571B1202). Int J Clin Oncol 13:244–251. doi:10.1007/s10147-007-0746-y

    Article  PubMed  CAS  Google Scholar 

  8. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216

    Article  PubMed  CAS  Google Scholar 

  9. Van der Abbeele AD, for the GIST PET study group (2001) F18-FDG-PET provides early evidence of biological response to STI571 in patients with malignant gastrointestinal stromal tumors (GIST). Proc Am Soc Clin Oncol 20:362a

    Google Scholar 

  10. Choi H, Charnsangavej C, Faria SC et al (2007) Correlation of Computed Tomography and Positron Emission Tomography of 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. doi:10.1200/JCO.2006.07.3049

    Article  PubMed  Google Scholar 

  11. Van den Abeele AD (2008) The lesions of GIST-PET and PET-CT: a new paradigm for imaging. Oncologist 13(Suppl 2):8–13. doi:10.1634/theoncologist.13-S2-8

    Article  Google Scholar 

  12. Lassau N, Chami L, Benatsou B et al (2007) Dynamic contrast-enhanced ultrasonography (DCE-US) with quantification of tumor perfusion: a new diagnostic tool to evaluate the early effects of antiangiogenic treatment. Eur Radiol 17(Suppl 6):F89–F98

    PubMed  Google Scholar 

  13. Italiano A, Bui B (2008) Gastrointestinal stromal tumors: molecular aspects and therapeutic implications. Bull Cancer 95:107–116. doi:10.1684/bdc.2008.0561

    PubMed  CAS  Google Scholar 

  14. Le Cesne A, Blay JY, Bui BN, Bouché O, Adenis A, Domont J, Cioffi A, Ray-Coquard I, Lassau N, Bonvalot S, Moussy A, Kinet JP, Hermine O (2010) Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST). Eur J Cancer 46(8):1344–1351. doi:10.1016/j.ejca.2010.02.014

    Article  PubMed  Google Scholar 

  15. Fletcher CD, Berman JJ, Corless C et al (2002) Diagnosis of gastrointestinal stromal tumors: a consensus approach. Int J Surg Pathol 10:81–89

    Article  PubMed  Google Scholar 

  16. Lassau N, Lamuraglia M, Chami L et al (2006) Gastrointestinal stromal tumors treated with imatinib: monitoring response with contrast-enhanced sonography. AJR Am J Roentgenol 187(5):1267–1273. doi:10.2214/AJR.05.1192

    Article  PubMed  Google Scholar 

  17. Antoch G, Kanja J, Bauer S et al (2004) Comparison of PET, CT and dual-modality PET/CT imaging for monitoring of imatinib (ST1571) therapy in patients with gastrointestinal stromal tumors. J Nucl Med 45:357–365

    PubMed  CAS  Google Scholar 

  18. Bauer A, Solbiati L, Weissman N (2002) Ultrasound imaging with SonoVue: low mechanical index real-time imaging. Acad Radiol 9(suppl 2):S282–S284

    Article  PubMed  Google Scholar 

  19. Peronneau P, Lassau N, Leguerney I, Cosgrove D (2010) Contrast ultrasonography: necessity of using linear data processing for quantification of tumor vascularisation. Ultraschall Med 31(4):370–378. doi:10.1055/s-0029-1245450

    Article  PubMed  CAS  Google Scholar 

  20. Lassau N, Chebil M, Chami L, Bidault S, Girad E, Roche A (2010) Dynamic contrast-enhanced ultrasonography (DCE-US): a new tool for the early evaluation of antiangiogenic treatment. Targeted Oncol 5(1):53–58. doi:10.1007/s11523-010-0136-7

    Article  Google Scholar 

  21. Lassau N, Chami L, Benatsou B, Peronneau P, Roche A (2007) Dynamic contrast-enhanced ultrasonography (DCE-US) with quantification of tumor perfusion: a new diagnostic tool to evaluate the early effects of antiangiogenic treatment. Eur Radiol 17(Suppl 6):F89–F98

    PubMed  Google Scholar 

  22. Lassau N, Brule A, Chami L, Benatsou B, Péronneau P, Roche A (2008) Evaluation of early response to antiangiogenic treatment with dynamic contrast enhanced ultrasound. J Radiol 89(5 Pt 1):549–555, doi:JR-5-2008-89-5-C1-0221-0363-101019-200802781

    Article  PubMed  CAS  Google Scholar 

  23. Lassau N, Koscielny S, Albiges L, Chami L, Benatsou B, Chebil M, Roche A, Escudier BJ (2010) Metastatic renal cell carcinoma treated with sunitinib: early evaluation of treatment response using dynamic contrast-enhanced ultrasonography. Clin Cancer Res 15; 16(4):1216–1225. doi:10.1158/1078-0432.CCR-09-2175

    Google Scholar 

  24. Lamuraglia M, Le Cesne A, Chami L, et al (2006) Dynamic contrast-enhanced Doppler ultrasound (DCE-US) is a useful radiological assessment to early predict the outcome of patients with gastrointestinal stromal tumors (GIST) treated with imatinib (IM). J Clin Oncol ASCO Annual Meeting Proceedings (Post Meeting Edition) June 20, Vol 24:529S

  25. Lamuraglia M, Escudier B, Chami L et al (2006) To predict progression-free survival and overall survival in metastatic renal cancer treated with sorafenib: pilot study using dynamic contrast enhanced Doppler ultrasound. Eur J Cancer 42(15):2472–2479. doi:10.1016/j.ejca.2006.04.023

    Article  PubMed  CAS  Google Scholar 

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Disclosure of funding received from any of the following organizations: NIH—Wellcome Trust, Howard Hughes Medical Institute and others.

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Authors and Affiliations

  1. Department of Medical Imaging, Ultrasonography Unit, Institut Gustave Roussy, University Paris-Sud, Villejuif, France

    Nathalie Lassau, Linda Chami, Mohamed Chebil, Baya Benatsou & Sophie Bidault

  2. Department of Statistics, Institut Gustave Roussy, University Paris-Sud, Villejuif, France

    Serge Koscielny

  3. Department of Medicine, Institut Gustave Roussy, University Paris-Sud, Villejuif, France

    Christophe Massard, Angela Cioffi & Axel Le Cesne

  4. Department of Medicine, University Claude Bernard Lyon I, Centre Léon Bérard, Lyon, France

    Jean-Yves Blay

  5. Imaging Department, Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94805, Villejuif Cedex, France

    Nathalie Lassau

  6. IR4M, University Paris-Sud, Orsay, France

    Nathalie Lassau

Authors
  1. Nathalie Lassau
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  2. Linda Chami
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  3. Serge Koscielny
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  4. Mohamed Chebil
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  6. Baya Benatsou
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  7. Sophie Bidault
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  8. Angela Cioffi
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  9. Jean-Yves Blay
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  10. Axel Le Cesne
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Correspondence to Nathalie Lassau or Christophe Massard.

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Lassau, N., Chami, L., Koscielny, S. et al. Quantitative functional imaging by Dynamic Contrast Enhanced Ultrasonography (DCE-US) in GIST patients treated with masatinib. Invest New Drugs 30, 765–771 (2012). https://doi.org/10.1007/s10637-010-9592-2

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  • DOI: https://doi.org/10.1007/s10637-010-9592-2

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