Metastatic duodenal GIST: role of surgery combined with imatinib mesylate
© Mohiuddin et al; licensee BioMed Central Ltd. 2007
Received: 14 February 2007
Accepted: 29 March 2007
Published: 29 March 2007
The best possible treatment of metastatic high grade large duodenal GIST is controversial. Surgery (with or without segmental organ resection) remains the principal treatment for primary and recurrent GIST. However, patients with advanced duodenal GIST have a high risk of early tumour recurrence and short life expectancy.
We present a case of a young man treated with a combined modality of surgery and imatinib for an advanced duodenal GIST.
He remains asymptomatic and disease free 42 months following this combined approach.
Treatment with imatinib has dramatically improved the outlook for patients with advanced, unresectable and/or metastatic disease.
Gastrointestinal stromal tumours or GISTs are the most common mesenchymal neoplasms of the gastrointestinal tract demonstrating positive c-kit (CD117) immunohistochemical staining. Approximately 50–70% originates in the stomach whereas 20–30% of from the small bowel, with duodenum being the least common site. Less frequent sites include the colon and rectum (5–15%) and esophagus (< 5%). These tumours usually grow submucosally but may also manifest as exophytic extraluminal subserosal growth. We report a case of a young man with a large extraluminal advanced duodenal GIST treated successfully with combination of surgery and imatinib mesylate.
Because of size of the tumour, histopathological and immunochemistry findings and the presence of tumour deposits in the adjacent mesocolon, the patient was given two years of imatinib mesylate therapy. A follow-up CT scans of chest, abdomen and pelvis have failed to reveal any evidence of recurrence. The patient is still alive and well without any signs of recurrence 42 months following this treatment.
Duodenal GIST can present with vague and non-specific symptoms such as upper abdominal pain (50% to 70%), gastrointestinal haemorrhage (20% to 50%) and an abdominal mass [1, 2]. A patient presenting with gastrointestinal haemorrhage may reveal a submucosal mass on endoscopy and biopsies are diagnostic in only 50% of cases . In our patient the endoscopy and biopsies were not helpful because the tumour was subserosal. The CT scan however raised the suspicion of duodenal GIST.
At laparotomy a large duodenal tumour on a narrow pedicle was encountered. It was felt that a wedge duodenal resection would be adequate provided tumour free margins could be obtained. A frozen section confirmed histologic tumour-free margins. Furthermore the adjacent mesocolon containing tumour deposit was also excised.
Parameters used in evaluation of GIST malignancy
Amin MB et al (1993)5
Kindblom et al (1998)6
Fletcher et al (1998)7
Panizo et al (2000)8
Trupiano et al (2002)9
Miettinen et al (2002)10
The overall 5 year survival for completely resected GISTs ranges from 30 – 80% . The relapse rate for patients having surgery ranges from 5% in those that have a complete resection, to 90% in those with unresectable and/or metastatic disease. The median survival for patients with unresectable and/or metastatic disease is 12 months (ranging from 2–20 months) . Patients with advanced stage disease have shown that the disease progresses after approximately 1.5 months without effective therapy .
Summary of Imatinib Trials
Multicentre Randomized USA Trial
Demetri et al NEJM 200215
400 mg od
600 mg od
34 months median
PR – 67%
SD – 16%
Survival – median
EORTC, ISG and AGITG
Van Glabbeke M et al Eur J Cancer16,17
400 mg od
400 mg bid
17 months median
CR – 6%
PR – 45%
SD – 33%
Survival – median
The Sarcoma Intergroup
Rankin et al Journal of Clinical Oncology 200418
400 mg od
800 mg od
24 months median
CR – 3%
PR – 45%
SD – 26%
Survival – median
Van Oosterum, Lancet 200119
Dose finding 400–1000 mg od
PR – 53%
SD – 16%
We felt that our patient being at an increased risk of recurrence because of his operative and histological findings, would need adjuvant treatment with imatinib (a) to stabilise his disease and (b) to prolong his recurrence-free period and survival. He was therefore started on 400 mg of imatinib once daily. He was followed up at six monthly intervals with a full body CT scan for the first two years. Surprisingly enough, he did not suffer from any major side effects from imatinib at all. At two years imatinib was stopped and further CT scans were performed at six monthly intervals which have not shown any evidence of recurrence and the patient remains asymptomatic and disease free at 42 months following his treatment. The future plan is to monitor him closely with CT scans for another eighteen months.
We feel that imatinib, a targeted tyrosine kinase inhibitor treatment in combination with surgery, has prolonged our patient's disease free survival and therefore have provided an effective adjuvant treatment for the metastatic duodenal GIST.
Conflict of interest/funding
The author(s) declare that they have no competing interests.
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