DOI: 10.1148/rg.262055097
RadioGraphics 2006;26:481-495
© RSNA, 2006
Gastrointestinal Stromal Tumor: Role of CT in Diagnosis and in Response Evaluation and Surveillance after Treatment with Imatinib1
Xie Hong, MD, PhD,
Haesun Choi, MD,
Evelyne M. Loyer, MD,
Robert S. Benjamin, MD,
Jonathan C. Trent, MD, PhD and
Chusilp Charnsangavej, MD
1 From the Departments of Diagnostic Radiology (X.H., H.C., E.M.L., C.C.) and Sarcoma Medical Oncology (R.S.B., J.C.T.), Unit 57, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. Recipient of a Certificate of Merit award for an education exhibit at the 2004 RSNA Annual Meeting. Received April 14, 2005; revision requested May 11 and received July 11; accepted July 11. H.C. and R.S.B. are consultants to and J.C.T. has received a research grant from the speakers bureau of Novartis Pharma, Basel, Switzerland; all other authors have no financial relationships to disclose.
Address correspondence to H.C. (e-mail: hchoi{at}mdanderson.org).
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Abstract
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Gastrointestinal stromal tumors (GISTs), which arise from the interstitial cells of Cajal, are the most common nonepithelial tumors of the gastrointestinal tract. It is now well known that imatinib, a new molecularly targeted tyrosine kinase receptor blocker, results in a dramatic response and markedly improved long-term survival in patients with GISTs. The increasing recognition of GISTs and the prolonged survival have made imaging increasingly important not only for diagnosis but also for monitoring the effects of treatment and detecting tumor progression. Computed tomography (CT) is the imaging modality of choice for these purposes. The imaging findings at initial presentation, during treatment, and at tumor progression were studied in 113 patients with primary and advanced GISTs before and up to 37 months after imatinib treatment. GISTs occur anywhere along the gastrointestinal tract, most commonly in the stomach and small bowel. At contrast material–enhanced CT, localized primary GISTs are typically exophytic, large, hypervascular masses. When the tumors respond to treatment, the changes in tumor size may initially vary; however, GISTs typically become homogeneous and hypoattenuating, with disappearance of enhancing tumor nodules and tumor vessels in the early posttreatment period. Development of a nodule within the treated tumor is unique to GISTs and indicates recurrence regardless of changes in tumor size.
© RSNA, 2006
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LEARNING OBJECTIVES FOR TEST 5
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After reading this article and taking the test, the reader will be able to:- List the clinical features and imaging findings of GISTs.
- Describe how GISTs can be diagnosed on the basis of the imaging findings.
- Discuss use of imaging in evaluating the response to imatinib treatment and in detecting tumor progression.
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Introduction
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Gastrointestinal stromal tumors (GISTs) are currently the most common nonepithelial tumors of the gastrointestinal tract, with an estimated 4500–6000 new cases reported each year in the United States (1). The term gastrointestinal stromal tumor was first used by Mazur and Clark (2) to describe an unusual type of nonepithelial tumor of the gastrointestinal tract that lacked the traditional features of smooth muscle or Schwann cells. GISTs are now thought to derive from a precursor of the interstitial cells of Cajal, normally present in the myenteric plexus, and are clearly distinct from other mesenchymal tumors, such as leiomyomas or leiomyosarcomas (3). The interstitial cells of Cajal normally express a trans-membrane receptor tyrosine kinase encoded by the KIT gene. Almost all GISTs express activating mutations in KIT that lead to ligand-dependent KIT tyrosine kinases activation and promote tumor survival and growth (4).
GISTs smaller than 2 cm are generally considered benign with a very low risk of recurrence. However, no GIST can truly be labeled benign (1). Histologically, GISTs manifest in one of three patterns: predominantly spindle cells (most common), predominantly epithelioid cells, or a mixture of spindle and epithelioid cells. Identifying KIT (CD117), a tyrosine kinase receptor in the interstitial cells of Cajal (5), is key to making a diagnosis of GIST in 95% of patients. The small number of GIST patients whose tumors do not express detectable KIT mutations instead express activating mutations in the related tyrosine kinase platelet-derived growth factor receptor alpha (PDGFR-
) (6). A definitive diagnosis is particularly important because advanced GIST can now be treated with the new tyrosine kinase inhibitor imatinib (Gleevec; Novartis Pharma, Basel, Switzerland) with a remarkable response (7) and a prolonged survival (8,9). Imatinib is a selective adenosine triphosphate (ATP)–competitive inhibitor of KIT, BCR-ABL, and PDGFR- and -ß. For KIT-negative GISTs, a tumor genotype assay to determine the mutational status of both the KIT and PDGFR- genes is recommended to establish a definitive diagnosis (1).
For localized primary GISTs, surgical resection is the mainstay of therapy (1). Use of a pre-operative biopsy of suspected GISTs has been controversial because of the potential risks of hemorrhage and tumor seeding into the peritoneal cavity. However, the prevalence of postbiopsy hemorrhage or tumor seeding is not yet known. Moreover, making a definite diagnosis on the basis of aspirated materials is difficult because of problems with inadequate sampling (10,11). A core biopsy is usually required with careful sampling of solid components by using a large-bore needle.
The increasing recognition of GISTs and the prolonged survival have made imaging increasingly important, not only for diagnosing the tumors but also for monitoring the effects of treatment and detecting tumor progression. Computed tomography (CT) is currently the modality of choice for these purposes, although different imaging techniques, such as fluorine 18 fluorode-oxyglucose (FDG) positron emission tomography (PET), magnetic resonance (MR) imaging, and ultrasonography (US), can also be used. FDG PET is highly sensitive in the detection of GISTs (12,13), but its access is limited worldwide; in addition, in a small number of lesions, glucose uptake by GISTs before treatment is insufficient for detection with FDG PET (14). MR imaging is indicated for surgical planning in cases of localized rectal GISTs, for evaluation of liver lesions indeterminate at CT, and for cases in which CT is contraindicated. In experts’ hands, US may also be useful to evaluate the liver.
This article describes the typical imaging findings of GISTs at initial presentation, during treatment with imatinib, and at tumor progression. Our observations are based on a review of the CT scans of 113 patients with primary and advanced GISTs treated at our institution; these scans were obtained between December 2000 and March 2004, both before and up to 37 months after imatinib treatment. These images were reviewed under the approval of the institutional review board. The findings at CT were correlated with those at FDG PET, when applicable. In addition, the radiologic findings related to drug toxic effects and technical aspects of CT are also described.
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Findings at Initial Presentation
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GISTs occur mostly in the stomach and small bowel but can occur anywhere along the gastrointestinal tract and uncommonly in the peritoneal cavity (1). Retroperitoneal GISTs are extremely rare (15). Of the 113 patients whose CT scans we reviewed, 42 (37%) had GISTs in the stomach (Figs 1–4), 37 (33%) in the small bowel (Figs 5, 6), 10 (9%) in the duodenum, five (4%) in the colon, six (5%) in the rectum (Figs 7, 8), two (2%) in the esophagus (Fig 9), and four (4%) in the peritoneum (Fig 10). In seven patients (6%), the location of the primary tumor was unknown.
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Figure 1. Gastric GIST in a 68-year-old woman who presented for an annual checkup with mild epigastric discomfort. The diagnosis was made with CT-guided biopsy. Contrast-enhanced CT scan shows a homogeneous extraluminal mass (arrow) arising from the greater curvature of the stomach. This appearance is typical of primary GIST. A subtotal gastrectomy was performed; there was no evidence of recurrence 18 months after surgery. The patient is currently undergoing surveillance.
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Figure 2. Gastric GIST in a 67-year-old man with rectorrhagia. A diagnosis of chronic gastritis was made at endoscopic biopsy. Contrast-enhanced CT scan shows an exophytic, slightly enhancing soft-tissue mass (long arrow) arising from the lesser curvature of the stomach. The oral contrast material (arrowheads) within the ulcerated mass is due to a fistula to the gastric lumen. To make the diagnosis, biopsy of one of the hepatic metastases (short arrows) was performed.
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Figure 3. Gastric GIST in a 72-year-old man with weakness. The diagnosis was made with exploratory laparotomy. Contrast-enhanced CT scan shows an unresectable gastric mass (arrowheads) completely surrounding the stomach. There is a small amount of contrast material (arrow) within the mass because of a fistula to the gastric lumen. Results of the initial endoscopic biopsy were negative for malignancy.
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Figure 4a. Small gastric GIST in a 42-year-old woman with Hodgkin lymphoma. The mass was detected at routine follow-up and diagnosed with endoscopic biopsy. (a) Contrast-enhanced CT scan shows a small (1.5-cm), exophytic mass (arrow) near the gastroesophageal junction. (b) Follow-up CT scan obtained 2 years later shows that the mass (arrow) has increased in size.
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Figure 4b. Small gastric GIST in a 42-year-old woman with Hodgkin lymphoma. The mass was detected at routine follow-up and diagnosed with endoscopic biopsy. (a) Contrast-enhanced CT scan shows a small (1.5-cm), exophytic mass (arrow) near the gastroesophageal junction. (b) Follow-up CT scan obtained 2 years later shows that the mass (arrow) has increased in size.
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Figure 5. Small bowel GIST in a 55-year-old woman who had abdominal discomfort but was otherwise healthy. The diagnosis was made with CT-guided biopsy. Contrast-enhanced CT scan shows a heterogeneous exophytic mass (white arrows) arising from the distal small bowel. Note the small fistula (black arrow) to the originating small bowel lumen.
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Figure 6. Small bowel GIST in a 50-year-old man. The mass was found incidentally during a work-up for prostate carcinoma and diagnosed with CT-guided biopsy. Contrast-enhanced CT scan shows a large, necrotic, exophytic mass (white arrowhead) arising from the ileum with a slightly enhancing solid component at the periphery. Note the multiple tumor vessels (black arrowheads) within the mass.
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Figure 7a. Small rectal GIST in an asymptomatic 66-year-old woman. The mass was found during an annual checkup and diagnosed with endoscopic biopsy. Axial T2-weighted (a) and contrast-enhanced T1-weighted (b) MR images obtained for a preoperative work-up show a small, enhancing, submucosal mass (arrow).
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Figure 7b. Small rectal GIST in an asymptomatic 66-year-old woman. The mass was found during an annual checkup and diagnosed with endoscopic biopsy. Axial T2-weighted (a) and contrast-enhanced T1-weighted (b) MR images obtained for a preoperative work-up show a small, enhancing, submucosal mass (arrow).
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Figure 8. Rectal GIST in a 39-year-old man with chronic back pain and worsening constipation. The diagnosis was made with endoscopic biopsy. Contrast-enhanced CT scan shows a slightly heterogeneous, massive perirectal mass (arrows), which is inseparable from the rectum with significant mass effect on the rectum. The mass was removed after imatinib treatment; it was found to have been located in the rectal wall.
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Figure 9. Esophageal GIST in a 40-year-old man with dysphagia. The diagnosis was made with endoscopic biopsy. Contrast-enhanced CT scan shows a large, exophytic, moderately enhancing mass (arrow) arising from the distal esophagus (E). This appearance is typical of primary GIST. The tumor recurred 18 months after esophagectomy.
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Figure 10. Extraintestinal GIST in a 36-year-old woman with a recent history of rectal prolapse. The diagnosis was made with surgical exploration. Contrast-enhanced CT scan shows a large, heterogeneous, moderately enhancing mass (arrows) at the rectovaginal septum; it is inseparable from both the vagina and the rectum. The mass replaced the rectovaginal connective tissue and was unresectable during the initial surgical exploration, but it was removed after treatment with imatinib. There has been no recurrence 22 months after surgery. The patient is currently undergoing surveillance.
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The clinical manifestations of GISTs depend on the location and size of the tumors and are often nonspecific. Common symptoms include early satiety, indigestion, bloating, vague abdominal pain, and a palpable mass. Occasionally, gastrointestinal bleeding occurs with tumors involving the mucosa (1). Because of these nonspecific clinical symptoms and the exophytic growth of the tumors, GISTs are often not detected until late in their progression.
The CT features of GISTs vary greatly, depending on the size and aggressiveness of the tumor and the time of presentation during the course of the disease. Primary GISTs are typically large, hypervascular, enhancing masses on contrast-enhanced CT scans and are often heterogeneous because of necrosis, hemorrhage, or cystic degeneration at the time of presentation (Figs 1–3, 5, 6, 8–10) (16,17). Ulceration and fistulization to the gastrointestinal lumen are also common features of GISTs (Figs 2, 3, 5) (16,17). Often, tumor vessels can be seen within the tumors (Fig 6). The masses usually displace adjacent organs and vessels, but direct invasion of the adjacent structures is sometimes seen with advanced disease (Fig 10). It can be difficult to identify the origin of the mass because of its large size and prominent extraluminal location. Bowel obstruction is rare.
Small GISTs can be endoluminal and polypoid in appearance. Small, localized GISTs are usually homogeneous and may be an incidental finding at CT or endoscopy (Figs 4, 7). Visibility with endoscopy is limited to smaller tumors, and results of endoscopic biopsy often can be nondiagnostic primarily because of insufficient tissue collection (10,11). Therefore, CT should be performed to follow up on suspected GISTs identified with endoscopy.
Nearly 50% of patients with GISTs present with metastasis (18). Most metastases of GISTs involve the liver and peritoneum by hematogenous spread and peritoneal seeding, respectively. Less commonly, metastases are found in the soft tissue, lungs, and pleura (Figs 11–14). Unlike gastrointestinal adenocarcinomas, GISTs metastasizing to the lymph nodes are extremely rare. The CT characteristics of metastatic lesions of GISTs are similar to those of primary tumors: hyperattenuating, enhancing masses that can be heterogeneous because of necrosis, hemorrhage, or cystic degeneration. Often, tumor vessels are evident within the tumors (Fig 13).
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Figure 11. Advanced jejunal GIST with multiple hepatic metastases in a 56-year-old man. Contrast-enhanced CT scan shows multiple small hepatic metastases with solid (black arrows) or rim (white arrows) enhancement. (Reprinted, with permission, from reference 14.)
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Figure 12. Advanced GIST with multiple peritoneal and soft-tissue metastases in a 64-year-old woman with recurrent small bowel GIST. Contrast-enhanced CT scan shows multiple heterogeneous, enhancing peritoneal masses (arrows) and an anterior subcutaneous mass (arrowhead).
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Figure 13. Advanced GIST with multiple hepatic and peritoneal metastases in a 68-year-old man with recurrent gastric GIST. Contrast-enhanced CT scan shows multiple bulky, heterogeneous masses (arrows) in the liver and peritoneum. Note the multiple small tumor vessels (arrowheads) in the tumors.
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Figure 14a. Advanced GIST with pleural and bilateral pulmonary metastases in a 46-year-old man with recurrent esophageal GIST. Contrast-enhanced CT scans show irregular soft-tissue masses along the left diaphragmatic pleura (straight arrows in a, arrows in b) and bilateral lung nodules (arrowheads in b). A postoperative change from an esophagectomy is also evident (curved arrow in a).
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Figure 14b. Advanced GIST with pleural and bilateral pulmonary metastases in a 46-year-old man with recurrent esophageal GIST. Contrast-enhanced CT scans show irregular soft-tissue masses along the left diaphragmatic pleura (straight arrows in a, arrows in b) and bilateral lung nodules (arrowheads in b). A postoperative change from an esophagectomy is also evident (curved arrow in a).
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Monitoring GISTs after Treatment with Imatinib
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Response Evaluation
Treatment with imatinib results in decreases in the size of GISTs, but this response typically takes several months before satisfying traditional tumor response criteria, such as the Response Evaluation Criteria in Solid Tumors (19). At contrast-enhanced CT, a response to imatinib is characterized by rapid transition from a heterogeneously hyperattenuating pattern to a homogeneously hypoattenuating pattern with resolution of the enhancing tumor nodules and a decrease in tumor vessels (Figs 15–17). Overall tumor attenuation decreases dramatically with the development of myxoid degeneration and, occasionally, hemorrhage or necrosis (Figs 15–17). The term cyst or cystic change should be avoided when describing the appearance of treated tumors at imaging. Although a decrease in the tumor attenuation is seen within 1 month in most of the responding GISTs, it may be seen as early as 5 days after treatment (unpublished data) or perhaps even earlier. The possibility of earlier detection of a tumor response at CT is being investigated.
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Figure 15a. Good response to imatinib in a 79-year-old woman with recurrent small bowel GIST with peritoneal implants. (a) Pretreatment contrast-enhanced CT scan shows a heterogeneous mesenteric mass with slight peripheral enhancement (arrows) abutting the liver. Note the tumor vessels (arrowhead) within the mass. (b, c) Follow-up CT scans show that the mass (large arrows) has become homogeneous and hypoattenuating, with significant decreases in the attenuation and size of the tumor 2 months after treatment (b) and further decreases 4 months after treatment (c). The tumor vessels are no longer evident. Such findings typify a good response to imatinib. A homogeneous hypoattenuating lesion in the liver (small arrow in c) is compatible with a treated hepatic metastasis.
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Figure 15b. Good response to imatinib in a 79-year-old woman with recurrent small bowel GIST with peritoneal implants. (a) Pretreatment contrast-enhanced CT scan shows a heterogeneous mesenteric mass with slight peripheral enhancement (arrows) abutting the liver. Note the tumor vessels (arrowhead) within the mass. (b, c) Follow-up CT scans show that the mass (large arrows) has become homogeneous and hypoattenuating, with significant decreases in the attenuation and size of the tumor 2 months after treatment (b) and further decreases 4 months after treatment (c). The tumor vessels are no longer evident. Such findings typify a good response to imatinib. A homogeneous hypoattenuating lesion in the liver (small arrow in c) is compatible with a treated hepatic metastasis.
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Figure 15c. Good response to imatinib in a 79-year-old woman with recurrent small bowel GIST with peritoneal implants. (a) Pretreatment contrast-enhanced CT scan shows a heterogeneous mesenteric mass with slight peripheral enhancement (arrows) abutting the liver. Note the tumor vessels (arrowhead) within the mass. (b, c) Follow-up CT scans show that the mass (large arrows) has become homogeneous and hypoattenuating, with significant decreases in the attenuation and size of the tumor 2 months after treatment (b) and further decreases 4 months after treatment (c). The tumor vessels are no longer evident. Such findings typify a good response to imatinib. A homogeneous hypoattenuating lesion in the liver (small arrow in c) is compatible with a treated hepatic metastasis.
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Figure 16a. Good response with a decrease in tumor attenuation after imatinib treatment in a 76-year-old man with recurrent gastric GIST with hepatic metastases. (a) Pretreatment contrast-enhanced CT scan shows multiple hypoattenuating hepatic metastases with slightly enhancing rims (arrows) in both lobes. (b) Contrast-enhanced CT scan obtained 2 months after treatment shows that the masses (arrows) have become homogeneous with a decrease in attenuation but have not substantially decreased in size.
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Figure 16b. Good response with a decrease in tumor attenuation after imatinib treatment in a 76-year-old man with recurrent gastric GIST with hepatic metastases. (a) Pretreatment contrast-enhanced CT scan shows multiple hypoattenuating hepatic metastases with slightly enhancing rims (arrows) in both lobes. (b) Contrast-enhanced CT scan obtained 2 months after treatment shows that the masses (arrows) have become homogeneous with a decrease in attenuation but have not substantially decreased in size.
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Figure 17a. Good response to imatinib treatment in a 71-year-old man with primary gastric GIST. (a) Contrast-enhanced CT scan shows a large, slightly heterogeneous mass (arrows) completely encasing or arising from the stomach. (b) Follow-up contrast-enhanced CT scan obtained 2 months after treatment shows that the mass (arrows) has become homogeneous with a significant decrease in attenuation, an appearance that typifies a good response to imatinib. (Reprinted, with permission, from reference 1.)
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Figure 17b. Good response to imatinib treatment in a 71-year-old man with primary gastric GIST. (a) Contrast-enhanced CT scan shows a large, slightly heterogeneous mass (arrows) completely encasing or arising from the stomach. (b) Follow-up contrast-enhanced CT scan obtained 2 months after treatment shows that the mass (arrows) has become homogeneous with a significant decrease in attenuation, an appearance that typifies a good response to imatinib. (Reprinted, with permission, from reference 1.)
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Paradoxically, tumors may enlarge during treatment. Enlargement of the tumor, if associated with an overall decrease in tumor enhancement, does not indicate progression (Figs 18, 19). Such enlargements can be due to development of an intratumoral hemorrhage or to myxoid degeneration.
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Figure 18a. Good response to imatinib treatment with increasing tumor size in a 51-year-old man with recurrent colon GIST with a peritoneal metastasis. (a) Pretreatment contrast-enhanced CT scan shows a peritoneal mass (arrow) with relatively low attenuation (42 HU). (b) Corresponding FDG PET scan shows markedly increased glucose uptake by the lesion (arrow). (c) Contrast-enhanced CT scan obtained 2 months after treatment shows that the mass (arrow) has become larger. However, the attenuation of the tumor has decreased (30 HU). (d) Corresponding FDG PET scan shows no appreciable glucose uptake by the lesion (arrow). The findings in c and d correlated with clinical improvement. Lack of a substantial decrease in tumor size during the early posttreatment period does not preclude a response to treatment. (Reprinted, with permission, from reference 14.)
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Figure 18b. Good response to imatinib treatment with increasing tumor size in a 51-year-old man with recurrent colon GIST with a peritoneal metastasis. (a) Pretreatment contrast-enhanced CT scan shows a peritoneal mass (arrow) with relatively low attenuation (42 HU). (b) Corresponding FDG PET scan shows markedly increased glucose uptake by the lesion (arrow). (c) Contrast-enhanced CT scan obtained 2 months after treatment shows that the mass (arrow) has become larger. However, the attenuation of the tumor has decreased (30 HU). (d) Corresponding FDG PET scan shows no appreciable glucose uptake by the lesion (arrow). The findings in c and d correlated with clinical improvement. Lack of a substantial decrease in tumor size during the early posttreatment period does not preclude a response to treatment. (Reprinted, with permission, from reference 14.)
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Figure 18c. Good response to imatinib treatment with increasing tumor size in a 51-year-old man with recurrent colon GIST with a peritoneal metastasis. (a) Pretreatment contrast-enhanced CT scan shows a peritoneal mass (arrow) with relatively low attenuation (42 HU). (b) Corresponding FDG PET scan shows markedly increased glucose uptake by the lesion (arrow). (c) Contrast-enhanced CT scan obtained 2 months after treatment shows that the mass (arrow) has become larger. However, the attenuation of the tumor has decreased (30 HU). (d) Corresponding FDG PET scan shows no appreciable glucose uptake by the lesion (arrow). The findings in c and d correlated with clinical improvement. Lack of a substantial decrease in tumor size during the early posttreatment period does not preclude a response to treatment. (Reprinted, with permission, from reference 14.)
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Figure 18d. Good response to imatinib treatment with increasing tumor size in a 51-year-old man with recurrent colon GIST with a peritoneal metastasis. (a) Pretreatment contrast-enhanced CT scan shows a peritoneal mass (arrow) with relatively low attenuation (42 HU). (b) Corresponding FDG PET scan shows markedly increased glucose uptake by the lesion (arrow). (c) Contrast-enhanced CT scan obtained 2 months after treatment shows that the mass (arrow) has become larger. However, the attenuation of the tumor has decreased (30 HU). (d) Corresponding FDG PET scan shows no appreciable glucose uptake by the lesion (arrow). The findings in c and d correlated with clinical improvement. Lack of a substantial decrease in tumor size during the early posttreatment period does not preclude a response to treatment. (Reprinted, with permission, from reference 14.)
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Figure 19a. Good response to imatinib treatment with increasing tumor size in a 41-year-old man with recurrent small bowel GIST with hepatic metastases. (a) Pretreatment contrast-enhanced CT scan shows multiple small, slightly hypoattenuating hepatic metastases (arrows). (b) Contrast-enhanced CT scan obtained 2 months after treatment shows that the lesions (arrows) have become homogeneous with decreased attenuation. However, the size of the tumors has increased. (c) Contrast-enhanced CT scan obtained 4 months after treatment shows that the lesion in the medial segment of the left lobe (long arrow) has significantly decreased in size. Note that the lesion in the right lobe (short arrow) has continued to increase in size but remains hypoattenuating. This lesion eventually became smaller on follow-up CT scans. (Reprinted, with permission, from reference 1.)
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Figure 19b. Good response to imatinib treatment with increasing tumor size in a 41-year-old man with recurrent small bowel GIST with hepatic metastases. (a) Pretreatment contrast-enhanced CT scan shows multiple small, slightly hypoattenuating hepatic metastases (arrows). (b) Contrast-enhanced CT scan obtained 2 months after treatment shows that the lesions (arrows) have become homogeneous with decreased attenuation. However, the size of the tumors has increased. (c) Contrast-enhanced CT scan obtained 4 months after treatment shows that the lesion in the medial segment of the left lobe (long arrow) has significantly decreased in size. Note that the lesion in the right lobe (short arrow) has continued to increase in size but remains hypoattenuating. This lesion eventually became smaller on follow-up CT scans. (Reprinted, with permission, from reference 1.)
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Figure 19c. Good response to imatinib treatment with increasing tumor size in a 41-year-old man with recurrent small bowel GIST with hepatic metastases. (a) Pretreatment contrast-enhanced CT scan shows multiple small, slightly hypoattenuating hepatic metastases (arrows). (b) Contrast-enhanced CT scan obtained 2 months after treatment shows that the lesions (arrows) have become homogeneous with decreased attenuation. However, the size of the tumors has increased. (c) Contrast-enhanced CT scan obtained 4 months after treatment shows that the lesion in the medial segment of the left lobe (long arrow) has significantly decreased in size. Note that the lesion in the right lobe (short arrow) has continued to increase in size but remains hypoattenuating. This lesion eventually became smaller on follow-up CT scans. (Reprinted, with permission, from reference 1.)
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The tumor response observed subjectively at CT, which is based on a decrease in or the disappearance of enhancing tumor nodules or tumor vessels or on a decrease in the overall tumor attenuation or size, correlates well with the response observed at FDG PET, which is based on a change in maximum standardized uptake value (14). An objective evaluation of tumor attenuation, measured in Hounsfield units, has been shown to be useful in early quantitative evaluation of tumor response (14,20,21). When the findings at CT are inconclusive or inconsistent with the clinical presentation, FDG PET should be performed (Fig 18). Short-term follow-up CT, perhaps within 1 month, can be a good alternative when FDG PET is not available.
Surveillance
Although surgical resection is the treatment of choice for primary GISTs, recurrence occurs in most patients, even after a complete resection with a tumor-free margin. The median time to recurrence after surgical resection is approximately 2 years (1). Once the tumors are resected or respond to imatinib treatment, the main goal of imaging is surveillance to detect recurrence or progression as early as possible.
Recurrences typically occur first in the liver or peritoneum. Traditional criteria for progression include tumor size increase, the development of new lesions at the site of the previous disease, and the development of metastasis (Fig 20). All of these criteria remain of value in monitoring patients with GISTs. The development of enhancing tumor nodules within the treated hypoattenuating tumor, regardless of changes in tumor size, is consistent with GIST recurrence (Figs 21, 22). This feature is unique to progressing GIST and should be kept in mind during surveillance. In our preliminary review, 40 (40%) of 101 patients with advanced GISTs had recurrences within 37 months of imatinib treatment, and 12 (30%) of these recurrences involved new intratumoral nodules or regrowth of residual but stable intratumoral nodules. The development of imatinib-resistant clones has been postulated to be responsible for such recurrences (22).
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Figure 20a. Recurrent small bowel GIST with a new peritoneal lesion at the site of previous disease in a 66-year-old woman. (a) Pretreatment contrast-enhanced CT scan shows multiple solid tumor implants (arrows) in the peritoneum and anterior abdominal wall. (b) On a contrast-enhanced CT scan obtained 14 months after treatment, the implants are no longer evident. (c) Contrast-enhanced CT scan obtained at 18-month follow-up shows a small recurrent lesion (arrow) at the site of previous disease. The lesion increased in size at 21-month follow-up.
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Figure 20b. Recurrent small bowel GIST with a new peritoneal lesion at the site of previous disease in a 66-year-old woman. (a) Pretreatment contrast-enhanced CT scan shows multiple solid tumor implants (arrows) in the peritoneum and anterior abdominal wall. (b) On a contrast-enhanced CT scan obtained 14 months after treatment, the implants are no longer evident. (c) Contrast-enhanced CT scan obtained at 18-month follow-up shows a small recurrent lesion (arrow) at the site of previous disease. The lesion increased in size at 21-month follow-up.
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Figure 20c. Recurrent small bowel GIST with a new peritoneal lesion at the site of previous disease in a 66-year-old woman. (a) Pretreatment contrast-enhanced CT scan shows multiple solid tumor implants (arrows) in the peritoneum and anterior abdominal wall. (b) On a contrast-enhanced CT scan obtained 14 months after treatment, the implants are no longer evident. (c) Contrast-enhanced CT scan obtained at 18-month follow-up shows a small recurrent lesion (arrow) at the site of previous disease. The lesion increased in size at 21-month follow-up.
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Figure 21a. Recurrence with new intratumoral nodules in a 59-year-old woman with recurrent gastric GIST in the omentum. (a) Pretreatment contrast-enhanced CT scan shows a large heterogeneous omental mass (arrows) with slight enhancement abutting the anterior surface of the stomach. (b, c) CT scans obtained 2 months (b) and 7 months (c) after treatment show that the mass (arrows) has become homogeneous with a decrease in attenuation and has progressively decreased in size. These findings indicate a good response to ima-tinib treatment. (d) Contrast-enhanced CT scan obtained 11 months after treatment shows two small nodules (arrows) within the mass. At surgery, the nodules were confirmed to be viable tumor tissue.
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Figure 21b. Recurrence with new intratumoral nodules in a 59-year-old woman with recurrent gastric GIST in the omentum. (a) Pretreatment contrast-enhanced CT scan shows a large heterogeneous omental mass (arrows) with slight enhancement abutting the anterior surface of the stomach. (b, c) CT scans obtained 2 months (b) and 7 months (c) after treatment show that the mass (arrows) has become homogeneous with a decrease in attenuation and has progressively decreased in size. These findings indicate a good response to ima-tinib treatment. (d) Contrast-enhanced CT scan obtained 11 months after treatment shows two small nodules (arrows) within the mass. At surgery, the nodules were confirmed to be viable tumor tissue.
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Figure 21c. Recurrence with new intratumoral nodules in a 59-year-old woman with recurrent gastric GIST in the omentum. (a) Pretreatment contrast-enhanced CT scan shows a large heterogeneous omental mass (arrows) with slight enhancement abutting the anterior surface of the stomach. (b, c) CT scans obtained 2 months (b) and 7 months (c) after treatment show that the mass (arrows) has become homogeneous with a decrease in attenuation and has progressively decreased in size. These findings indicate a good response to ima-tinib treatment. (d) Contrast-enhanced CT scan obtained 11 months after treatment shows two small nodules (arrows) within the mass. At surgery, the nodules were confirmed to be viable tumor tissue.
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Figure 21d. Recurrence with new intratumoral nodules in a 59-year-old woman with recurrent gastric GIST in the omentum. (a) Pretreatment contrast-enhanced CT scan shows a large heterogeneous omental mass (arrows) with slight enhancement abutting the anterior surface of the stomach. (b, c) CT scans obtained 2 months (b) and 7 months (c) after treatment show that the mass (arrows) has become homogeneous with a decrease in attenuation and has progressively decreased in size. These findings indicate a good response to ima-tinib treatment. (d) Contrast-enhanced CT scan obtained 11 months after treatment shows two small nodules (arrows) within the mass. At surgery, the nodules were confirmed to be viable tumor tissue.
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Figure 22a. Recurrence with a new intratumoral nodule in a 72-year-old man with duodenal GIST metastatic to the liver. (a) Contrast-enhanced CT scan obtained 12 months after treatment shows a tiny nodule (arrow) within a hypoattenuating metastasis in the right lobe of the liver. (b, c) Follow-up contrast-enhanced CT scans obtained 17 months (b) and 22 months (c) after treatment show that the enhancing nodule (arrow in b, arrowhead in c) has progressively increased in size. At 22-month follow-up, the nodule completely fills the mass (arrow in c). The mass eventually became enlarged as well. (Reprinted, with permission, from reference 1.)
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Figure 22b. Recurrence with a new intratumoral nodule in a 72-year-old man with duodenal GIST metastatic to the liver. (a) Contrast-enhanced CT scan obtained 12 months after treatment shows a tiny nodule (arrow) within a hypoattenuating metastasis in the right lobe of the liver. (b, c) Follow-up contrast-enhanced CT scans obtained 17 months (b) and 22 months (c) after treatment show that the enhancing nodule (arrow in b, arrowhead in c) has progressively increased in size. At 22-month follow-up, the nodule completely fills the mass (arrow in c). The mass eventually became enlarged as well. (Reprinted, with permission, from reference 1.)
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Figure 22c. Recurrence with a new intratumoral nodule in a 72-year-old man with duodenal GIST metastatic to the liver. (a) Contrast-enhanced CT scan obtained 12 months after treatment shows a tiny nodule (arrow) within a hypoattenuating metastasis in the right lobe of the liver. (b, c) Follow-up contrast-enhanced CT scans obtained 17 months (b) and 22 months (c) after treatment show that the enhancing nodule (arrow in b, arrowhead in c) has progressively increased in size. At 22-month follow-up, the nodule completely fills the mass (arrow in c). The mass eventually became enlarged as well. (Reprinted, with permission, from reference 1.)
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A recent report from the National Comprehensive Cancer Network suggests that recurrent GISTs should be managed as metastatic disease (1). The clinical significance and management of local recurrence in an asymptomatic patient are still being debated. However, it is important to identify these recurrences as soon as possible because early local treatment, such as ablation or local resection, can be offered (1). Conversely, tumor progression should not be assumed in the presence of an enlarging mass devoid of new or enlarging enhancing nodules (Figs 18, 19).
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Special Issues
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Adverse Effects of Imatinib: Fluid Overload and Hemorrhage
The adverse effects of imatinib include fluid retention (most common), diarrhea, nausea, fatigue, muscle cramps, abdominal pain, and rash (1). Treatment-related fluid overload may manifest as ascites, a pleural effusion, a pericardial effusion, or extensive subcutaneous edema (Fig 23). Consequently, any new ascites noted on CT scans should not be mistakenly interpreted as indicating new peritoneal disease, when the disease is otherwise stable or resolving. Although adverse effects are usually very mild, intratumoral hemorrhages can occur in approximately 5% of patients with bulky tumors and may require surgical intervention. Careful observation is needed to detect possible decreases in hemoglobin levels during the first 4–8 weeks of imatinib treatment. As noted earlier, an intratumoral hemorrhage can increase the tumor size, wrongly suggesting progression; in addition, it can spuriously increase the tumor attenuation, thus complicating the response evaluation (Fig 24).
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Figure 23a. Development of fluid retention as an adverse effect of imatinib in a 64-year-old woman with metastatic small bowel GIST. (a) Pretreatment contrast-enhanced CT scan shows multiple heterogeneous and enhancing masses in the peritoneum (black arrow) and anterior subcutaneous tissue (white arrow). (b) On a follow-up contrast-enhanced CT scan obtained 2 months after treatment, the masses (arrows) have become smaller. Note the new ascites (*). New ascites should not be misinterpreted as an indicator of new peritoneal disease when the disease is otherwise improving.
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Figure 23b. Development of fluid retention as an adverse effect of imatinib in a 64-year-old woman with metastatic small bowel GIST. (a) Pretreatment contrast-enhanced CT scan shows multiple heterogeneous and enhancing masses in the peritoneum (black arrow) and anterior subcutaneous tissue (white arrow). (b) On a follow-up contrast-enhanced CT scan obtained 2 months after treatment, the masses (arrows) have become smaller. Note the new ascites (*). New ascites should not be misinterpreted as an indicator of new peritoneal disease when the disease is otherwise improving.
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Figure 24a. Development of an intratumoral hemorrhage as an adverse effect of imatinib in a 60-year-old woman with recurrent small bowel GIST in the liver. (a) Pretreatment contrast-enhanced CT scan shows multiple heterogeneous hepatic metastases with moderately enhancing solid nodules at the peripheries (arrows). Prominent tumor vessels (arrowheads) are noted within the masses. (b) Contrast-enhanced CT scan obtained 2 months after imatinib treatment shows that the tumors (arrows) have become homogeneous and the enhancing tumor nodules have markedly resolved, indicating a good response to the treatment. (c) Unenhanced CT scan from the same data acquisition shows a fluid-fluid level within the smaller tumor (black arrow); the fluid-fluid level was caused by an intratumoral hemorrhage. The attenuation of the smaller tumor increased from 73 HU to 115 HU. White arrow = larger tumor.
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Figure 24b. Development of an intratumoral hemorrhage as an adverse effect of imatinib in a 60-year-old woman with recurrent small bowel GIST in the liver. (a) Pretreatment contrast-enhanced CT scan shows multiple heterogeneous hepatic metastases with moderately enhancing solid nodules at the peripheries (arrows). Prominent tumor vessels (arrowheads) are noted within the masses. (b) Contrast-enhanced CT scan obtained 2 months after imatinib treatment shows that the tumors (arrows) have become homogeneous and the enhancing tumor nodules have markedly resolved, indicating a good response to the treatment. (c) Unenhanced CT scan from the same data acquisition shows a fluid-fluid level within the smaller tumor (black arrow); the fluid-fluid level was caused by an intratumoral hemorrhage. The attenuation of the smaller tumor increased from 73 HU to 115 HU. White arrow = larger tumor.
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Figure 24c. Development of an intratumoral hemorrhage as an adverse effect of imatinib in a 60-year-old woman with recurrent small bowel GIST in the liver. (a) Pretreatment contrast-enhanced CT scan shows multiple heterogeneous hepatic metastases with moderately enhancing solid nodules at the peripheries (arrows). Prominent tumor vessels (arrowheads) are noted within the masses. (b) Contrast-enhanced CT scan obtained 2 months after imatinib treatment shows that the tumors (arrows) have become homogeneous and the enhancing tumor nodules have markedly resolved, indicating a good response to the treatment. (c) Unenhanced CT scan from the same data acquisition shows a fluid-fluid level within the smaller tumor (black arrow); the fluid-fluid level was caused by an intratumoral hemorrhage. The attenuation of the smaller tumor increased from 73 HU to 115 HU. White arrow = larger tumor.
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Technical Issues
The liver is the most common organ for GIST metastasis. As with primary GISTs, hepatic metastasis is hypervascular and as such can be unrecognized on enhanced CT scans obtained during the portal venous phase. A "new" homogeneous and hypoattenuating lesion without definite enhancing nodules observed on an enhanced CT scan after imatinib treatment should not be mistaken for disease progression. Both unenhanced and enhanced CT scans should be thoroughly analyzed to avoid erroneous interpretation of such a lesion (Fig 25).
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Figure 25a. Spurious new hepatic lesion in a 59-year-old woman with gastric GIST metastatic to the liver. (a–c) Unenhanced (a), early arterial phase (b), and late arterial phase (c) pretreatment CT scans show an enhancing mass (arrow) in the left lobe of the liver. (d) On a portal venous phase CT scan, the mass (arrow) is invisible. (e) Portal venous phase CT scan obtained 2 months after treatment clearly shows the mass (arrow) owing to its decreased enhancement, which indicates a good response to the treatment. (Reprinted, with permission, from reference 1.)
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Abstract
LEARNING OBJECTIVES FOR TEST...
