English

Abstract

Introduction Gastrointestinal stromal tumours (GISTs) represent a major fraction of gastrointestinal sarcomas, frequently showing c-kit exon 11 mutations and associated with a good response to imatinib mesylate. Secondary resistance to imatinib has also been reported during therapy; therefore, clinicians need non-invasive tools for early assessment of treatment response due to traditional morphologic criteria [X-rays and computerized tomography (CT)] being unsuccessful. We report upon a patient with GIST with exon 11 mutation showing excellent response to imatinib mesylate, only a few days after initiation of the therapy and persisting for 18 months of follow-up. Here we also provide a short review of the recent literature on this topic. Conclusion There is evidence that F-FDG PET and PET/CT could be used to optimally monitor c-kit inhibitor therapy in GISTs, detecting early responders, non-responders and secondary resistance, there by allowing better patient management. Introduction Gastrointestinal stromal tumours (GISTs) are rare malignancies even though they represent the most relevant part of the gastrointestinal (GI) tract sarcomas. In most cases, GISTs are localized in the stomach and small intestine, followed by the colon and rectum1. GISTs are derived from Cajal cells in myenteric plexus; they are frequently marked by the expression of the c-kit tyrosine kinase receptor1. C-kit is a tyrosine kinase and is normally activated as a ligand by stem cell factor; a mutation of the c-kit proto-oncogene activates the tyrosine kinase in the absence of physiologic stimulation, there by leading to unrestrained cell proliferation2. The majority of GISTs (75%–80%) shows gain-of-function mutations of transmembrane receptor c-kit, which causes continuous activation of cell proliferation. The most common is the exon 11 mutation3. Genetic mutation analysis allows investigation of the relationship between the mutations occurred and response to drugs, such as imatinib mesylate. Imatinib mesylate is a tyrosine kinase inhibitor of tumour growth, and it has been demonstrated to be effective in GIST treatment. It is currently the first-line drug in advanced GISTs4. Recent studies3,5 show that 85% patients with c-kit exon 11 mutation respond to imatinib mesylate; nevertheless, it has been reported that resistance to this drug may occur during therapy6. This phenomenon needs to be disclosed as early as possible to change the therapeutic strategy, improve the clinical outcome and reduce the cost of ineffective therapies. In this regard, the response evaluation criteria in solid tumours (RECIST) criteria which relates to morphological examinations, mainly contrastenhanced computed tomography (CT), are unsatisfactory in assessment of GISTs response because changes in tumour size may be minimal at an early post-therapy evaluation or the lesion could be even larger because of intra-tumoural necrosis or haemorrhage7,8. There is recent evidence that a functional imaging modality such as 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) or a hybrid imaging modality such as PET/ CT could achieve this goal9–11. This paper reports the case of a GIST patient treated with imatinib mesylate and showing an excellent response as documented by 18F-FDG PET/CT only a few days after initiation of the therapy and persisting for 18 months of follow-up. We also reviewed the relevant literature pertaining to the response monitoring tools in GISTs. Discussion In April 2008, a 54-year-old male patient underwent surgery for GIST T2N0M0 with mutation of exon 11. In August 2010, a controlled CT revealed bone and liver GIST metastasis that was proven at biopsy. Therapy with imatinib mesylate was scheduled. Before initiating therapy, the patient underwent baseline 18F-FDG PET/CT and repeated an early PET/CT examination 10 days after initiation of the therapy. Subsequent PET/CT controls during imatinib mesylate therapy * Corresponding author Email: domenico.rubello@libero.it † Current address: Nuclear Medicine and Radiology Unit, Morgagni-Pierantoni Hospital, Forli, Italy 1 Department of Nuclear Medicine, Medical Physics, Radiology, Neuroradiology, PET/ CT Centre, ‘Santa Maria della Misericordia’ Hospital, Via Tre Martiri 140, 45100 Rovigo, Italy 2 Department of Medical Physics, ‘Santa Maria della Misericordia’ Hospital, Rovigo, Italy 3 Department of Oncology, ‘Santa Maria della Misericordia’ Hospital, Rovigo, Italy Em er gi ng T ec hn ol og ie s