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

Abstract

ObjectiveWe 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 MethodsIn 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.ResultsThe 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.ConclusionTwo distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management.

Rapidly progressive dyspnea in gastrointestinal stromal tumor (GIST) with imatinib cardiac toxicity

“…Prospective data on cardiac function and long-term follow-up data are needed to confirm murine observation in humans. Kim et al and Trent et al both have described a rapidly progressive heart failure with imatinib-treated GIST in a small series of patients, consistent with the current case in which dyspnea manifested just 2 weeks after dose initiation [5,6]. …”

“…Acute fluid retention in Kim’s series was noted at 0.3–4.0 months (median ~2 months) after dose escalation or imatinib initiation. In contrast to literature assertions, acute fluid retention presentations were more severe, and more likely in younger patients with fewer comorbidities [5,6]. In general, elderly with preexisting cardiovascular comorbidities might be more prone to chemotherapeutic toxicity; but, in the current case, dose-dependent toxicity seems more likely.…”

“…Thus, the authors concluded that fluid retention was not associated with imatinib cardiotoxicity [5]. Incidence of cardiotoxicity was cited as similar to onset of heart failure incidence in the general population, estimated at 0.2% per year, as evidenced by new-onset heart failure or left ventricular dysfunction [5].…”

“…Thus, the authors concluded that fluid retention was not associated with imatinib cardiotoxicity [5]. Incidence of cardiotoxicity was cited as similar to onset of heart failure incidence in the general population, estimated at 0.2% per year, as evidenced by new-onset heart failure or left ventricular dysfunction [5]. While the impact of imatinib cardiotoxicity for GIST has been debated, molecular re-engineering of anticancer C-kit kinase inhibitors and cellular data on mitochondrial dysfunction and adenosine triphosphate (ATP) production deficit in murine models suggest a relationship, despite advocates for imatinib safety [11–14].…”

Cardiotoxicity of anticancer treatments

“…Such agents can alter afterload (through blood-pressure elevation) or preload (through fluid retention). 12,13 Furthermore, upon alteration of loading relationships that add stress to the myocardium, exacerbation or acceleration of the rate of cell death can occur. Rather than directly inducing toxicity, these anticancer agents potentiate a secondary insult that, in some instances, is reversible with correction of the adverse haemodynamic changes.…”