Molecular response of gastrointestinal stromal tumour after treatment with tyrosine kinase inhibitor imatinib mesylate

Division of Medical Oncology, Hematology, and Tumour Immunology, Robert Roessle Hospital and Tumour Institute, Charité University Hospital, The Humboldt University at Berlin, D-13122 Germany.
Journal of Clinical Pathology (Impact Factor: 2.92). 03/2004; 57(2):215-7.
Source: PubMed


Bleeding from the tumour site is not uncommon during the treatment of gastrointestinal stromal tumours with imatinib mesylate. It might represent an early reaction of highly vascularised tumour tissue to receptor blockade. Although often requiring emergency surgery, this is not necessarily a deleterious sign. Slow tumour regression and cystic tissue alteration may follow. Using immunohistochemistry and consecutive resection specimens, it was shown that the number of mitoses decreased significantly and MIB-1 as a marker of cell proliferation could no longer be detected. In the few tumour cells still present, the magnitude of expression of the pathognomonic marker CD117 remained unchanged. Decreases in the size of tumours responding to imatinib mesylate cannot be expected to meet the World Health Organisation or RECIST (response evaluation criteria in solid tumours) criteria. This underlines the necessity of functional imaging by positron emission tomography, contrast enhanced magnetic resonance imaging, or magnetic resonance spectroscopy to assess the response to treatment.

Download full-text


Available from: Christian Stroszczynski, Sep 29, 2014
10 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Unresectable or metastatic gastrointestinal stromal tumors (GISTs) exhibit a dynamic clinical course, with no evidence of benefit from any standard cytotoxic chemotherapy and an inevitably fatal outcome. With the introduction of Imatinib, an oral drug able to inhibit the KIT receptor tyrosine kinase, new questions arise regarding our ability to monitor treatment response with conventional methods and optimally manage such patients on treatment with new agents. Herein we report two cases of patients with a history of GIST in treatment with Imatinib. After 4 weeks from treatment start, CT scan evaluation demonstrated a massive increase in the size of metastatic lesions, but a confirmatory PET excluded, in both patients, the presence of any metabolic activity in the previously known metastatic sites. Imatinib therapy was continued with subjective clinical benefit for 12 further months before a PET scan-confirmed disease progression had occurred in one patient and is still ongoing after 15 months in the other. These cases open the obvious question of whether conventional imaging techniques are adequate to assess the response to Imatinib treatment in GIST patients.
    Anticancer research 01/2004; 24(5B):3147-51. · 1.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Niedermolekulare synthetische Moleküle (small molecules) haben in jüngster Zeit erhebliches Interesse für die Behandlung solider Tumoren gefunden. Sie richten sich vorwiegend gegen Rezeptoren der Signaltransduktion (Tyrosinkinasen, EGF), die für die Proliferation bei manchen Subtypen maligner Tumoren von entscheidender Bedeutung sind. Während die EGF-Rezeptorblockade hinsichtlich der dadurch gebotenen therapeutischen Optionen noch schwer abschätzbar ist, hat die Blockade von c-kit, einem homologen Stammzellfaktor bei der CML und bei gastrointestinalen Stromatumoren, bereits einen festen Stellenwert erreicht. Die Beeinflussung von PDGF-, von VEGF- oder anderen Rezeptoren beruht meist auf der Blockade der kristallografisch ermittelten Struktur der Kinasedomäne mit Behinderung der Phosphorylierung. Das Medikamenten-Engineering ist hierbei von entscheidender Bedeutung, aber auch die Subklassifikation von Malignomen, um tatsächlich denjenigen Tumortyp zur Behandlung zu bringen, bei dem der blockierbare Rezeptor einen oder den entscheidenden Schritt der Tumorproliferation darstellt. Hierfür sind Genexpressionsstudien auf der Basis von Mikroarrays eine wichtige Voraussetzung. Da unklar ist, wie lange eine Rezeptorblockade anhält, sollte bei Resektabilität des Residualtumors der operative Eingriff angestrebt werden. Zu berücksichtigen ist, dass für Operationen unter den Bedingungen der Rezeptorblockade noch wenige Erfahrungen vorliegen. Die Aufklärung der Resistenzmechanismen gegenüber small molecules hat für die CML und GIST gerade begonnen und verspricht wichtige Aufschlüsse über intratumorale Anpassungsvorgänge an medikamentöse Rezeptorblockaden zu liefern.
    Der Onkologe 01/2004; 10(1). DOI:10.1007/s00761-003-0637-4 · 0.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Typical MRI findings for gastro-intestinal stromal tumours (GIST) under treatment with imatinib were evaluated. MRI was performed in 45 patients (25 responders, 20 non-responders) with metastatic or locally advanced, unresectable GIST. Target lesions were selected and re-evaluated after 2, 4, and 6 months of therapy with imatinib. The target tumour response (TTR) was classified according to RECIST criteria. TTR, signal intensity in the centre and border of the lesion and the presence and the extension of a hypervascular rim were analysed. The mean diameter of the marker lesions decreased significantly (P<0.001) from 7.1+/-2.6 cm to 5.9+/-2.3 cm after 6 months. Accuracy of RECIST criteria was 51%, 69% and 73% on MRI 2, 4 and 6 months for response assessment. In addition, responders had higher signal-to-noise ratios on T2-w images after 2 months (P<0.05) and a decrease of vascularised areas in the lesion 4 and 6 months after treatment (each P<0.01), when compared with non-responders. Beyond the size measurement for response assessment, MRI provides additional information of tumour response using SI of T2-w images and quantification of vascularised areas of GIST manifestations.
    European Radiology 01/2006; 15(12):2448-56. DOI:10.1007/s00330-005-2867-x · 4.01 Impact Factor
Show more