Assessment of sorafenib induced changes in tumor perfusion of uveal melanoma metastases with dynamic contrast-enhanced ultrasound (DCE-US)

Dane Wildner,Deike Strobel,Rolf Janka,Eckhart Kaempgen,Max E Scheulen,Joerg Sturm,Ferdinand Knieling,Gerold Schuler,Markus F Neurath,Lucie Heinzerling

doi:10.1007/s00432-021-03666-8

Abstract

PurposeDynamic contrast-enhanced ultrasound (DCE-US) was used to monitor early response to sorafenib therapy in patients with liver metastases from uveal melanoma.MethodsIn total, 21 patients with liver metastases were recruited within a prospective trial and underwent daily sorafenib therapy. DCE-US of a target lesion was performed before initiation of treatment, on day 15 and 56. Two independent blinded investigators performed software analysis for DCE-US parameters and inter-observer-correlation was calculated. Response to treatment was evaluated on day 56. DCE-US parameters were correlated with clinical response and RECIST1.1 criteria.ResultsInter-observer-correlation (r) of DCE-US parameters [time-to-peak (TTP), mean-transit-time (MTT), peak intensity (PI), regional blood volume (RBV), regional blood flow (RBF)] at baseline, day 15, and day 56 was highly significant (r-range 0.73–0.97, all p < 0.001). Out of 17 evaluable patients, 12 patients survived day 56 (clinical responders, cRE), whereas, five patients died before day 56 and were classified as non-responders (cNR). TTP values significantly increased in the cRE group 15 days after initiation of treatment for investigator 1 (p = 0.034) and at day 56 for both investigators (p = 0.028/0.028). MTT had increased significantly in the cRE group on day 56 (p = 0.037/0.022). In the cNR group changes for TTP and MTT remained insignificant. Thus, increase of the DCE-US parameters TTP and MTT are associated with response to treatment and prognosis.ConclusionAn increase of TTP and MTT at frequent intervals could serve as a surrogate marker for early response evaluation to anti-angiogenic treatment of metastatic uveal melanoma.

Highlights

Uveal melanoma is the most frequent primary intraocular malignant tumor in adults (Chattopadhyay et al 2016)
Even though sorafenib did not show convincing effectiveness in metastatic cutaneous melanoma, an effect was postulated in uveal melanoma known for the high vascularization of metastases
Clinical trials evaluated the efficacy of sorafenib in the treatment of patients with metastatic uveal melanoma (Carvajal et al 2017; Mouriaux et al 2016; Scheulen et al 2017)

Summary

Introduction

Uveal melanoma is the most frequent primary intraocular malignant tumor in adults (Chattopadhyay et al 2016). Treatment for patients with cutaneous melanoma has significantly improved, but this progress could not be transferred to patients with uveal melanoma. Uveal melanoma remains a tumor entity with limited therapy options and for which effective treatment approaches are lacking (Carvajal et al 2017). Even though sorafenib did not show convincing effectiveness in metastatic cutaneous melanoma, an effect was postulated in uveal melanoma known for the high vascularization of metastases. Clinical trials evaluated the efficacy of sorafenib in the treatment of patients with metastatic uveal melanoma (Carvajal et al 2017; Mouriaux et al 2016; Scheulen et al 2017)

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