DOI:10.2214/AJR.04.1516
AJR 2006; 186:510-515
© American Roentgen Ray Society
MDCT Appearance of Gastrointestinal Stromal Tumors After Therapy with Imatinib Mesylate
Dinuke R. Warakaulle1 and
Fergus Gleeson1
1 Both authors: Department of Radiology, The Churchill Hospital, Old Road,
Oxford, OX3 7LJ, United Kingdom.
Received September 25, 2004;
accepted after revision January 14, 2005.
Address correspondence to D. R. Warakaulle
(dinuke2{at}hotmail.com).
Abstract
OBJECTIVE. Our objective was to determine the MDCT appearance of
gastrointestinal stromal tumors (GISTs) after treatment with imatinib
mesylate.
CONCLUSION. Cystic changes within primary and metastatic GISTs seen
on MDCT in patients after imatinib mesylate therapy are evidence of disease
response. Calcification may also occur in lesions that respond to therapy.
Keywords: CT • gastrointestinal imaging • gastrointestinal stromal tumors • imatinib mesylate • oncologic imaging
Introduction
Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms that
arise from precursors of the connective tissue cells of the gastrointestinal
tract. About 70% arise in the stomach, 20-30% in the small intestine, and
fewer than 10% in the remainder of the gastrointestinal tract, and the tumors
occur predominantly in middle-aged and elderly patients
[1]. The most specific
diagnostic criterion for GIST is immunohistochemical staining that is positive
for CD117, which detects a tyrosine kinase receptor that is a product of the
c-kit protooncogene, which mutates to become constitutionally active
in these tumors [2].
Malignant GISTs have a variable imaging appearance. They have been
described as typically large, well-circumscribed tumors that arise in the wall
of the stomach or small bowel. They rarely obstruct viscera and have a
propensity to metastasize to the liver and peritoneum
[3]. Central cystic changes at
the time of diagnosis have been shown to be more common in large (> 3 cm in
diameter) tumors [4]. Large
tumors, irregular and poorly defined margins, invasion of adjacent structures,
heterogeneous enhancement, hepatic metastases, and peritoneal dissemination on
imaging have been shown to correlate with high-grade tumors and an unfavorable
prognosis [5].
Until the advent of imatinib mesylate, treatment with systemic chemotherapy
and local radiation therapy had little impact on surgically unresectable
disease [6].
Imatinib mesylate is a phenylaminopyrimidine derivative that selectively
inhibits the enzymatic activity of several tyrosine kinases, including the
BCR-ABL fusion protein of chronic myeloid leukemia and Philadelphia
chromosome-positive acute lymphoblastic leukemia and the product of the
c-kit protooncogene. Joensuu et al.
[7] showed that imatinib
mesylate caused disease regression in a patient with recurrent unresectable
GIST. Chen et al. [8] also
reported a similar response to imatinib mesylate in four patients with hepatic
metastases from GISTs. All eight hepatic lesions followed up in this study
showed cystic changes after therapy.
The aim of this study was to evaluate the MDCT appearance of inoperable
GISTs in patients treated with imatinib mesylate.
Materials and Methods
The pharmaceutical database of The Churchill Hospital was reviewed to
obtain a list of patients who had been prescribed imatinib mesylate (Glivec,
Novartis) over a 5-year period (March 2000 to March 2004). Five patients were
identified as satisfying the selection criteria and constituted our study
group. These data were then cross-referenced with the histopathologic database
to determine which of these patients had been treated for biopsy-proven,
c-kit-positive GISTs. The MDCT examinations of all these patients
were reviewed. Only patients with inoperable tumors received imatinib mesylate
therapy.
All examinations were performed on an 8-MDCT scanner (LightSpeed Ultra, GE
Healthcare). Images were obtained in the portal venous phase after the IV
administration of 100 mL of iodinated contrast medium (Niopam 300 [iopamidol],
Amersham Health) at a slice thickness of 5.0 mm and at 15.0-mm intervals. The
images were viewed on a workstation using software supplied with the imaging
system. Only axial images were viewed. The images were interpreted by one of
the authors, a radiologist experienced in oncologic and gastrointestinal
cross-sectional imaging. Follow-up imaging was performed after three or six
cycles of chemotherapy, depending on the oncologists' preferences.
Results
In three of the patients we reviewed, the lesions responded to imatinib
mesylate therapy (Table 1). In
two of these patients, the primary and metastatic lesions became smaller and
showed extensive cystic changes. The primary tumor in the third patient did
not change significantly in size but did undergo extensive cystic changes. In
this context, the term "cystic change" as used by Chen et al.
[8] and in our report describes
markedly lower attenuation in the tumor than in skeletal muscle on
contrast-enhanced CT. The study of Chen et al.
[8] showed that GISTs with
cystic changes had higher attenuation values than did simple cysts, although
they might have appeared visually similar. One lesion in our series showed
punctate calcification on a follow-up study, a feature not previously
described.
Two patients showed disease progression despite imatinib mesylate therapy.
The tumor masses in both patients increased in size, and there was no
significant relative increase in the cystic components of the tumors.
Discussion
CT is widely used for staging gastrointestinal malignancies and for
monitoring response to therapy. GISTs are rare tumors for which no effective
therapy was available for inoperable cases until the advent of imatinib
mesylate. The CT appearance of these tumors has been described previously
[3,
4]. Chen et al.
[8] evaluated the CT appearance
of hepatic metastases from GISTs in four patients treated with imatinib
mesylate. Most metastatic lesions became smaller after therapy, and all
exhibited cystic changes with well-defined borders on contrast-enhanced CT.
The case reported by Joensuu et al.
[7] showed hepatic metastases
with similar changes. These radiologic appearances are not typically seen in
cancer that responds to conventional chemotherapy or radiation therapy.
Histologic examination of GISTs treated with imatinib mesylate has shown that
some of these lesions undergo myxomatous changes
[6]. This avascular, amorphous
myxoid material is likely to correspond to the uniformly low-attenuation
cystic changes seen on contrast-enhanced CT.
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Fig. 2B —83-year-old man presenting with weight loss and altered bowel habit.
Follow-up studies after chemotherapy show progressive reduction in size and
extensive cystic changes in these lesions.
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Fig. 2C —83-year-old man presenting with weight loss and altered bowel habit.
Follow-up studies after chemotherapy show progressive reduction in size and
extensive cystic changes in these lesions.
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The efficacy of imatinib mesylate in the treatment of GISTs remains to be
proven in a large-scale clinical trial. The therapy is costly, with a daily
400-mg dose for a single 30-day cycle currently costing £1,829 (
$3,363). Monitoring the efficacy of therapy by accurately quantifying disease
response on imaging is therefore important. PET performed with
18F-FDG has been shown to be superior to CT for the detection of
early response to therapy [9]
and for the accurate separation of responders from nonresponders in the early
phase of therapy [10].
However, MDCT provides a more readily accessible means of monitoring response
to therapy and is the technique of choice for initial staging and often for
imaging-guided biopsy. A study performed by Antoch et al.
[11] showed that CT was able
to detect a response to therapy 1 month after its commencement, although the
accuracy of CT was less than that of 18F-FDG PET. In our opinion,
it would be reasonable to begin monitoring treatment response 1 month after
commencing therapy—that is, at the end of the first cycle—with
follow-up imaging at 3 and 6 months.
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Fig. 3A —85-year-old man presenting with chest wall mass. He had previously
undergone gastrectomy for gastrointestinal stromal tumor. Images from staging
CT study show lesion in right anterior chest wall (A, arrow)
and lobulated mass in upper abdomen (B, arrow).
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Fig. 3B —85-year-old man presenting with chest wall mass. He had previously
undergone gastrectomy for gastrointestinal stromal tumor. Images from staging
CT study show lesion in right anterior chest wall (A, arrow)
and lobulated mass in upper abdomen (B, arrow).
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Fig. 3C —85-year-old man presenting with chest wall mass. He had previously
undergone gastrectomy for gastrointestinal stromal tumor. Follow-up studies
after chemotherapy show resolution of chest wall mass (C) and
progressive shrinkage of upper abdominal lesion, with extensive cystic changes
(D and E).
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Fig. 3D —85-year-old man presenting with chest wall mass. He had previously
undergone gastrectomy for gastrointestinal stromal tumor. Follow-up studies
after chemotherapy show resolution of chest wall mass (C) and
progressive shrinkage of upper abdominal lesion, with extensive cystic changes
(D and E).
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Fig. 3E —85-year-old man presenting with chest wall mass. He had previously
undergone gastrectomy for gastrointestinal stromal tumor. Follow-up studies
after chemotherapy show resolution of chest wall mass (C) and
progressive shrinkage of upper abdominal lesion, with extensive cystic changes
(D and E).
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Fig. 4A —52-year-old woman presenting with right iliac fossa mass. She had
previously undergone resection of small bowel because of gastrointestinal
stromal tumor. Axial CT image shows large pelvic mass and mass in right
anterior abdominal wall.
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Fig. 4B —52-year-old woman presenting with right iliac fossa mass. She had
previously undergone resection of small bowel because of gastrointestinal
stromal tumor. Follow-up studies after chemotherapy show progressive growth of
these lesions (B and C) and new satellite nodule in anterior
abdominal wall (C, arrow).
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Fig. 4C —52-year-old woman presenting with right iliac fossa mass. She had
previously undergone resection of small bowel because of gastrointestinal
stromal tumor. Follow-up studies after chemotherapy show progressive growth of
these lesions (B and C) and new satellite nodule in anterior
abdominal wall (C, arrow).
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Fig. 5B —61-year-old man presenting with neurofibromatosis, type I, and right
iliac fossa mass. Repeated studies after patient's acute presentation show
enlargement of mass (B). An air-fluid level is seen within mass, with
loop of bowel closely apposed to it (C). These features are of
malignant fistula.
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Fig. 5C —61-year-old man presenting with neurofibromatosis, type I, and right
iliac fossa mass. Repeated studies after patient's acute presentation show
enlargement of mass (B). An air-fluid level is seen within mass, with
loop of bowel closely apposed to it (C). These features are of
malignant fistula.
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In conlcusion, a reduction in tumor size, extensive cystic changes, and
calcification in primary and metastatic GISTs on MDCT indicate a disease
response. Extensive cystic changes could be interpreted as a response to
therapy even in the absence of a reduction in size of the tumor mass.
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Abstract
Introduction
