Korean J Radiol.  2015 Apr;16(2):304-313. 10.3348/kjr.2015.16.2.304.

Fluid Retention Associated with Imatinib Treatment in Patients with Gastrointestinal Stromal Tumor: Quantitative Radiologic Assessment and Implications for Management

• Kim KW
• Shinagare
• Krajewski
• Pyo J
• Tirumani S
• Jagannathan JP
• Ramaiya NH

• KMID: 2070174
• DOI: http://doi.org/10.3348/kjr.2015.16.2.304

Abstract

OBJECTIVE
We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management.
MATERIALS AND METHODS
In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores.
RESULTS
The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction.
CONCLUSION
Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management.

Keyword

Imatinib; Fluid retention; Subcutaneous edema; Ascites; Computed tomography

MeSH Terms

Adult
Aged
Aged, 80 and over
Antineoplastic Agents/*adverse effects/therapeutic use
Ascites/pathology/radiography
Benzamides/*adverse effects/therapeutic use
Echocardiography/methods
Edema/pathology/radiography
Female
Gastrointestinal Stromal Tumors/drug therapy/pathology/*radiography
Gastrointestinal Tract/pathology/*radiography
Heart Failure/radiography
Humans
Male
Middle Aged
Molecular Targeted Therapy/*adverse effects
Pericardial Effusion/pathology/radiography
Peritoneal Neoplasms/diagnosis/radiography/secondary
Piperazines/*adverse effects/therapeutic use
Pleural Effusion/pathology/radiography
Pyrimidines/*adverse effects/therapeutic use
Radiology
Retrospective Studies
Tomography, X-Ray Computed
Antineoplastic Agents
Benzamides
Piperazines
Pyrimidines

Figure

• 

  Fig. 1 Grade of subcutaneous edema. In 71-year-old female with gastrointestinal stromal tumor (case 6), subcutaneous edema occurred as mild form involving less than half of abdominal wall at 1st follow-up CT (A) after initiation of imatinib 400 mg, and aggravated to moderate form involving more than half of abdominal wall at 2nd follow-up CT (B) obtained shortly after dose escalation from 400 to 800 mg, followed by severe circumferential subcutaneous edema at 3rd follow-up CT (C).

• 

  Fig. 2 Time-course of radiologic signs of fluid retention (FR) of all patients. Vertical axis represents total score and each score of radiologic signs of FR and transverse axis represents time from imatinib initiation. Nine patients (cases 1-9) show acute/progressive FR, while six patients (cases 10-15) show only intermittent/steady FR, with mild persistent FR or occasional episode of mild FR. AS = ascites, PC = pericardial effusion, PL = pleural effusion, SE = subcutaneous edema

• 

  Fig. 3 Time-course of acute/progressive fluid retention (FR) in patients of group 1. Vertical axis represents total score of radiologic signs of FR, and transverse axis represents time from imatinib initiation or recent dose escalation. Acute/progressive FR occurs in early period after imatinib initiation or recent dose escalation (9/9, 100%), with median time to maximum FR 1.9 months and median score of maximum FR 5. Thick gray line is representative line of time-course of exacerbation periods with time to peak 1.9 months and peak height 5.

• 

  Fig. 4 Proportion of type of radiologic fluid retention of group 1 (A) and group 2 (B). In all types of fluid retention, proportion and severity were higher in group 1 compared to group 2. AS = ascites, PC = pericardial effusion, PL = pleural effusion, SE = subcutaneous edema

• 

  Fig. 5 67-year-old male with gastrointestinal stromal tumor presented with new ascites (case 11). A. Axial contrast-enhanced CT (CECT) shows new small ascites in pelvic cavity (arrow) adjacent to peritoneal metastasis in pelvic cavity (arrowheads), 10 days after starting imatinib treatment. Mild subcutaneous edema is also newly apparent. B. Axial image of CECT shows scrotal edema (curved arrows). Based on scrotal edema, subcutaneous edema, and stability of peritoneal metastasis, new small ascites occurred early after starting imatinib may be manifestation of fluid retention rather than malignant ascites.

• 

  Fig. 6 Relationship between total score of radiologic fluid retention (FR) and imatinib dose (A) or management level of FR (B). A. Scatterplot shows moderate positive correlation (r = 0.526) between total score of radiologic FR and imatinib dose. B. Strong positive correlation (r = 0.879) between level of management and total score of radiologic FR was observed on scatterplot.

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