Gastrointestinal stromal tumors treated with imatinib: monitoring response with contrast-enhanced sonography.

OBJECTIVE The purpose of this study was to evaluate contrast-enhanced Doppler sonography with perfusion software as a predictor of early tumor response to imatinib (Glivec) in c-kit-positive gastrointestinal stromal tumors (GISTs). SUBJECTS AND METHODS Thirty patients (59 tumors) with metastases or a recurrence from a GIST were prospectively included in a single-center imaging trial. Contrast-enhanced Doppler sonography was performed with an Aplio scanner the day before (day-1) starting oral treatment (400 mg) and at days 1, 7, 14, 60, 90, and 6 months, 9 months, and 1 year. The percentage of contrast uptake (Levovist or Sonovue) before treatment and at the different stages of follow-up was evaluated by two radiologists. Digitized quantification was performed using Photoshop software. To define the benchmark standard, all patients were rated as responders or nonresponders at 2 and 6 months by a board consisting of oncologists and radiologists who had all clinical and imaging data at their disposal. Changes in the percentage of contrast uptake at each sonographic examination were compared statistically. RESULTS A total of 185 examinations were performed. Forty-four lesions in 24 patients were completely evaluated at 2 months, and 29 lesions in 15 patients were completely evaluated at 6 months. Initial contrast uptake at day 1 was predictive of the future response. A strong correlation was found between the decline in tumor contrast uptake at days 7 and 14 and tumor response (p < 10(-4)). CONCLUSION Contrast-enhanced Doppler sonography is a noninvasive imaging technique that allows the early prediction of tumor response in c-kit-positive GIST treated with Glivec.

[1]  Sigrid Stroobants,et al.  Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group. , 2002, European journal of cancer.

[2]  C. J. Chen,et al.  KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. , 2001, Cancer research.

[3]  D. Tuveson,et al.  Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. , 2001, The New England journal of medicine.

[4]  S. Koscielny,et al.  New hemodynamic approach to angiogenesis: color and pulsed Doppler ultrasonography. , 1999, Investigative radiology.

[5]  P. Hohenberger,et al.  Molecular response of gastrointestinal stromal tumour after treatment with tyrosine kinase inhibitor imatinib mesylate , 2004, Journal of Clinical Pathology.

[6]  E. Gaffney,et al.  Gastrointestinal stromal tumours , 2003, The British journal of surgery.

[7]  E. Kotter,et al.  Computed tomography in gastrointestinal stromal tumors , 2003, European Radiology.

[8]  J. Berman,et al.  Gastrointestinal stromal tumor workshop. , 2001, Human pathology.

[9]  D. Podoloff,et al.  The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[10]  Nathalie Lassau,et al.  Validation of a New Method for Quantifying In Vivo Murine Tumor Necrosis by Sonography , 2004, Investigative radiology.

[11]  K. Antman,et al.  Imatinib mesylate--a new oral targeted therapy. , 2002, The New England journal of medicine.

[12]  J. Blay,et al.  Limb salvage with isolated perfusion for soft tissue sarcoma: could less TNF-α be better? , 2005 .

[13]  T. de Baère,et al.  Prognostic value of angiogenesis evaluated with high-frequency and color Doppler sonography for preoperative assessment of melanomas. , 2002, AJR. American journal of roentgenology.

[14]  D. Vanel,et al.  Value of high-frequency US for preoperative assessment of skin tumors. , 1997, Radiographics : a review publication of the Radiological Society of North America, Inc.

[15]  A. Kovatich,et al.  CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. , 1998, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[16]  J Nuyts,et al.  18FDG-Positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Glivec). , 2003, European journal of cancer.

[17]  N. Lassau,et al.  Évaluation fonctionnelle et précoce des traitements en cancérologie : intérêt des produits de contraste ultrasonores , 2004 .

[18]  S. Bonvalot,et al.  [Treatment of local recurrent melanomas by isolated limb perfusion: value of Doppler ultrasonography]. , 2003, Journal de radiologie.

[19]  L. Sobin,et al.  Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site. , 1999, The American journal of surgical pathology.

[20]  P. Terrier,et al.  Doppler US with perfusion software and contrast medium injection in the early evaluation of isolated limb perfusion of limb sarcomas: prospective study of 49 cases. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[21]  A. Eggert,et al.  Loss of caspase-8 mRNA expression is common in childhood primitive neuroectodermal brain tumour/medulloblastoma. , 2002, European journal of cancer.

[22]  E. Levine,et al.  Cystic changes in hepatic and peritoneal metastases from gastrointestinal stromal tumors treated with Gleevec , 2003, Abdominal Imaging.

[23]  V. Velanovich,et al.  Evaluation of Gastrointestinal Stromal Tumors for Recurrence Rates and Patterns of Long-Term Follow-Up , 2004, The American surgeon.

[24]  Sigrid Stroobants,et al.  Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study , 2001, The Lancet.

[25]  N Weissman,et al.  Ultrasound imaging with SonoVue: low mechanical index real-time imaging. , 2002, Academic radiology.

[26]  P. Opolon,et al.  Evaluation of Contrast-Enhanced Color Doppler Ultrasound for the Quantification of Angiogenesis In Vivo , 2001, Investigative radiology.

[27]  A. D. Van den Abbeele,et al.  Use of positron emission tomography in oncology and its potential role to assess response to imatinib mesylate therapy in gastrointestinal stromal tumors (GISTs). , 2002, European journal of cancer.

[28]  S. Koscielny,et al.  Prognostic value of high-frequency sonography and color Doppler sonography for the preoperative assessment of melanomas. , 1999, AJR. American journal of roentgenology.

[29]  S. Whittaker,et al.  EORTC Cutaneous Lymphoma Task Force , 2002 .

[30]  J. Blay,et al.  Interruption of imatinib (IM) in GIST patients with advanced disease: Updated results of the prospective French Sarcoma Group randomized phase III trial on survival and quality of life , 2005 .

[31]  A. D. Van den Abbeele,et al.  Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. , 2002, The New England journal of medicine.

[32]  Gerald Antoch,et al.  Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[33]  N. Moriyama,et al.  Gastrointestinal Stromal Tumor: Correlation of Computed Tomography Findings with Tumor Grade and Mortality , 2003, Journal of computer assisted tomography.

[34]  R. Bechtold,et al.  Cystic changes in hepatic metastases from gastrointestinal stromal tumors (GISTs) treated with Gleevec (imatinib mesylate). , 2002, AJR. American journal of roentgenology.

[35]  G. Demetri,et al.  Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib , 2004 .