CT-based response assessment of advanced gastrointestinal stromal tumor: Dual energy CT provides a more predictive imaging biomarker of clinical benefit than RECIST or Choi criteria

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Abstract

Objectives

Dual-energy CT (DECT) allows quantification of intravenously injected iodinated contrast media in tumors, and therefore may be considered as a surrogate marker for perfusion and tumor vascularity. This study evaluated whether newly developed DECT response criteria allow better correlation with survival than established response criteria.

Methods

Seventeen patients with advanced GIST treated with tyrosine-kinase-inhibitors were assessed by contrast-enhanced DECT 2 and 6 months after beginning of treatment. Response to treatment of 165 tumor lesions was evaluated according to RECIST, Choi criteria and newly developed DECT criteria, defining non-responders as an increase of both tumor size >20% and iodine related attenuation or either a >50% increase of tumor size or iodine related attenuation. All other patients were classified as responders. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan–Meier analysis.

Results

Choi criteria and DECT showed a significantly longer median PFS of patients rated as responders than patients rated as non-responders (9–29 months vs. 2–6 months; p < 0.02) at follow-up. Only DECT analysis at 6 months follow-up allowed a valid prediction of OS.

Conclusion

This study indicates that DECT allows a better prediction of therapeutic benefit in advanced GIST patients treated with tyrosine-kinase-inhibitors than established response criteria. However, the most important predictive biomarker of therapeutic benefit was absence of progression, no matter which response evaluation criteria were applied.

Introduction

Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor of the gastrointestinal tract, with an incidence of approximately 5–15 per million persons in Western World [1]. While radical surgery is the treatment of choice for located GISTs, targeted therapy with tyrosine-kinase inhibitors like imatinib or sunitinib has become the treatment of choice for metastatic disease [1], [2]. Since the introduction of these molecularly targeted drugs, there has been increasing concern about the use of traditional tumor response criteria (e.g. WHO or RECIST) [3], as several studies have indicated that response to treatment is not equivalent to a change in tumor size. In fact, tumor activity not necessarily correlates with immediate size changes, as a biologic resistance to treatment may be apparent between 6 and 12 months before a radiologic progression is confirmed according to RECIST [4]. Interestingly, it has been demonstrated that patients classified as responders or stable disease (SD) according to RECIST have equal overall survival (OS), with the most important predictive marker of therapeutic benefit being absence or presence of progression [5]. Further, targeted therapies induce changes in lesion structure, often resulting in a decrease in tumor density, decrease in enhancement of intratumoral nodules, and decrease in tumor vessels that are consistent with therapeutic activity with or without a change in tumor volume [4], [6], [7]. Therefore, Choi et al. have proposed alternative response criteria which besides tumor size also consider changes in tumor density [6], [8], [9].

The attenuation or density of a lesion on portal venous CT can be considered as the sum of density on unenhanced CT and the change of density induced by the contrast enhancement after injection of iodinated contrast media. Dual energy CT (DECT) allows selective quantification and visualization of this iodinate based contrast agent differences, the so-called iodine-related attenuation (IRA) [10], [11]. Hence, two recent studies suggested that DECT IRA may be a more precise parameter in monitoring target therapies in GIST patients than Choi criteria [12], [13].

The aim of this study was to evaluate whether DECT allows a better correlation with survival than either Choi criteria or RECIST in patients with advanced GIST under target therapies.

Section snippets

Patient population

In this retrospective study we analyzed the data of 19 patients treated for histologically proven, advanced GIST at our institution. All patients received therapy with tyrosine kinase inhibitors and underwent DECT between July 2007 and August 2011. Due to the retrospective nature of the study, the institutional review board (IRB) approval was waived, but information gathered on this population was performed in compliance with Health Insurance Portability and Accountability Act (HIPAA) and the

Determination of the DECT response criteria

Non-responders were defined as those who showed new lesions on follow-up evaluation or showed an in abnormal increase in lesion size according to RECIST. Further those who experience a therapy change or died within 6 months of their follow-up examination were also classified as non-responders. Therefore the new DECT assessment criteria were established on the ground of the following findings: First when looking at all lesions rated as non-responders, 95% of them showed a 20% increase in tumor

Discussion

The distinctly favorable clinical response to kinase-targeted drugs as first, second- and third line treatment options have redefined the clinical management and prognosis of patients with GIST. Further it has initiated studies to optimize response evaluation strategies in target therapies by noninvasive imaging. Currently measurement of tumor response to antineoplastic agents in GIST patients is performed according to RECIST and the Choi criteria. The choi criteria were established from data

Conflict of interest

None to declare.

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1

Tel.: +49 621 383 2067; fax: +49 621 383 3817.

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Tel.: +49 621 383 2357; fax: +49 621 383 1430.

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