Early Metabolic Response as a Predictor of Treatment Outcome in Patients With Metastatic Soft Tissue Sarcomas

Abstract

Background/Aim: Pazopanib is approved for advanced soft tissue sarcoma (STS) patients. The aim of the study was to examine the usefulness of ( 18 F)-Fluorodeoxyglucose-positron emission tomography/ computed tomography (FDG-PET/CT) imaging for early evaluation of the response of STS patients to pazopanib, as well as the association between pazopanib pharmacokinetics and early metabolic response. Patients and Methods: Twenty STS patients underwent FDG-PET scans at baseline, two-and eight-weeks following treatment with pazopanib. The FDG-PET scans were evaluated by quantitative PERCIST analysis and visually by an independent nuclear medicine physician and related to RECIST1.1 outcome at eight weeks. Results: After eight weeks of therapy, 14 out of 20 patients had discontinued pazopanib due to tumor progression identified radiologically ('non-responders' n=12) or toxicity (n=2). Quantitative FDG-PET scoring at two weeks, according to PERCIST guidelines, identified 25% (3 of 12) of the patients radiologically as non-responders versus 42% (5 of 12) identified by visual response analysis. Conclusion: In this heterogeneous STS patients' cohort, early FDG-PET/CT identified a substantial part of pazopanib non-responders.Soft tissue sarcomas (STS) represent a group of rare mesenchymal cancers that encompasses more than 70 histological subtypes (1). Based on the outcome of the PALETTE trial, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved pazopanib as the first oral targeted therapy for non-gastrointestinal stromal tumors (GIST), non-adipocytic STS patients in second line and beyond (2). Patients treated with pazopanib showed a progression-free survival (PFS) benefit of 3 months compared to placebo-treated patients. Unfortunately, 23% of patients had progressive disease and were considered as de novo resistant to pazopanib therapy (non-responders), and about 10-30% of the STS patients treated with pazopanib developed grade 3-4 toxicity (2, 3). It is, therefore, evident that easily assessable biomarkers to predict response shortly after the start of treatment with pazopanib are required to identify patients who will ultimately not benefit from therapy. This is particularly important to avoid treatment of patients with an ineffective, potentially toxic, and expensive drug over a prolonged period of time. Molecular imaging with ( 18 F)-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) has shown clinical relevance for grading and staging sarcoma patients (4); reflecting outcome after (neoadjuvant) chemotherapy (5, 6); and for predicting the anti-tumor effect of imatinib in GIST patients (7, 8) at an earlier stage than is currently possible with conventional radiological imaging that solely depicts tumor morphology (CT/MRI). In addition, FDG-PET/CT has been successful in predicting the effects of angiogenesis inhibitors in metastatic renal cell carcinoma (mRCC) (9).Until now, the metabolic response depicted by FDG-PET/CT has not been related to drug pharmacokine...

Sarcoma treatment in the era of molecular medicine

“…It is interesting to note that advances in imaging technology have paved the way for imaging modalities that are capable of defining drug response at earlier stages of treatment. As an example, the use of FDG‐PET after 2 weeks of treatment with pazopanib was able to correctly classify 42% of STS patients as non‐responders (Vlenterie et al , 2019).…”

Usefulness of 18f-FDG PET-CT in Staging, Restaging, and Response Assessment in Pediatric Rhabdomyosarcoma

“…In the second case (Figure 2), the 18 F-FDG PET-CT played a major role in giving both an accurate evaluation of the disease extent (staging and restaging) and a metabolic prognostic factor TLR that Baum et al [14] have correlated with the survival rate [19]. Our two cases are not a suggestion to use only serial 18 F-FDG PET-CT in the follow-up of these patients, but they represent an invitation to consider, as many works suggest [20][21][22][23][24], that the provided metabolic information could be extremely useful in the disease management, with an estimated 21% overall potential benefit of PET-CT over CT/MRI, in the "upstaging" of high-grade disease, as Macpherson et al demonstrated in a recent work [20].…”

Princípios básicos e aplicações oncológicas da PET-CT/18F-FDG

“…A partir destes dados, a PET-CT/ 18 F-FDG pode ser uma metodologia importante para a mudança de dosagens e incorporação de reforços terapêuticos em decisões futuras. De acordo com Vlenterie et al 34 , os achados de PET-CT associados ao PERCIST identificaram que 25% dos pacientes com sarcoma metastático de tecidos moles não foram responsivos ao tratamento de duas semanas com o Pazopanib, sugerindo a PET-CT/ 18 F-FDG como um biomarcador precoce para predizer a progressão da doença.…”