Abstract
The outcome of high-risk soft tissue sarcoma (STS) is poor with radical surgery being the only potentially curative modality. Pazopanib is a multikinase inhibitor approved for the treatment of metastatic STS. Herein, in terms of the German Interdisciplinary Sarcoma Group (GISG-04/NOPASS) trial, we evaluate the potential role of kinetic analysis of fludeoxyglucose F-18 (18F-FDG) data derived from the application of dynamic positron emission tomography/computed tomography (PET/CT) in response assessment to pazopanib of STS patients scheduled for surgical resection. Sixteen STS patients treated with pazopanib as neoadjuvant therapy before surgery were enrolled in the analysis. All patients underwent dynamic PET/CT prior to and after pazopanib treatment. Data analysis consisted of visual (qualitative) analysis of the PET/CT scans, semi-quantitative evaluation based on standardized uptake value (SUV) calculations, and quantitative analysis of the dynamic 18F-FDG PET data, based on two-tissue compartment modeling. Resection specimens were histopathologically assessed and the percentage of regression grade was recorded in 14/16 patients. Time to tumor relapse/progression was also calculated. In the follow-up, 12/16 patients (75%) were alive without relapse, while four patients (25%) relapsed, among them one patient died. Median histopathological regression was 20% (mean 26%, range 5–70%). The studied population was dichotomized using a histopathological regression grade of 20% as cut-off. Based on this threshold, 10/14 patients (71%) showed partial remission (PR), while stable disease (SD) was seen in the rest 4 evaluable patients (29%). Semi-quantitative evaluation showed no statistically significant change in the widely used PET parameters, SUVaverage and SUVmax. On the other hand, 18F-FDG kinetic analysis revealed a significant decrease in the perfusion-related parameter K1, which reflects the carrier-mediated transport of 18F-FDG from plasma to tumor. This decrease can be considered as a marker in response to pazopanib in STS and could be due to the anti-angiogenic effect of the therapeutic agent.
Highlights
The outcome of high-risk soft tissue sarcoma (STS) is poor
Out of the 21 patients enrolled in the GISG-04/NOPASS trial [5], sixteen STS patients had evaluable dynamic positron emission tomography/computed tomography (PET/CT) both pre- and post treatment, and were enrolled in the analysis
The parameter K1 could be potentially used as an early response marker of the anti-angiogenic effect of pazopanib with changes of this parameter being used for therapeutic management decisions, after taking into account other tumor-related parameters
Summary
The outcome of high-risk soft tissue sarcoma (STS) is poor. Radical surgery, usually in combination with radiotherapy, is the mainstay of treatment and the only potentially curative modality [1]. Be cumbersome due to the large tumor size with infiltration of adjacent structures, and extensive tumor vasculature [2]. In this context, the development and application of a fast acting, preoperative STS therapy that would facilitate tumor resection and at the same time have low toxicity would be of high significance. Pazopanib is a multikinase inhibitor, approved for the treatment of metastatic STS based on a phase III trial in patients with non-adipocytic STS, who had progressed on at least one prior chemotherapy regimen [3]. Given this proof of efficacy, and its favorable safety profile [4], the German
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