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

PURPOSE: Dynamic contrast-enhanced ultrasound (DCE-US) was used to monitor early response to sorafenib therapy in patients with liver metastases from uveal melanoma. METHODS: In 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. RESULTS: Inter-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. CONCLUSION: An 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.

Cost-utility analysis of a decade of liver screening for metastases using the Liverpool Uveal Melanoma Prognosticator Online (LUMPO).

This paper outlines a method for cost-utility analysis of liver screening for metastases in patients with posterior uveal melanoma (UM). A semiparametric model of the cumulative incidence of onset of liver metastases was fitted to a retrospective data set of 615 subjects with clinical follow-up with respect to liver surveillance imaging and outcome. The model was internally validated via bootstrap resampling in terms of its discrimination and calibration performance. Receiver operating characteristics (ROC) were derived at different time points. The discrimination performances are consistent across time. The area under the ROC curve at 5 years post treatment was 0.85 [95% CI: 0.81-0.88]. A goodness-of-fit test gives χ2(10)=5.3,p=0.9 demonstrating no evidence against the null hypothesis of zero difference between observed and expected onset of metastatic events. Results showed that at 80% sensitivity, 87% of UM patients will avoid unnecessary radiological scans. This provides potential cost savings of between £46,000 and £97,000 per year to the National Health Service assuming 600 new cases per year.

Uveal melanoma: quantitative evaluation of diffusion-weighted MR imaging in the response assessment after proton-beam therapy, long-term follow-up.

PURPOSE: The purpose of this prospective study was to investigate the proton-beam-induced changes in apparent diffusion coefficient (ADC) values of ocular melanoma treated with proton-beam therapy (PBT) in patients undergoing long-term magnetic resonance imaging (MRI) follow-up and to assess whether variations in ADC constitute a reliable biomarker for predicting and detecting the response of ocular melanoma to PBT. METHODS: Seventeen patients with ocular melanoma treated with PBT were enrolled. All patients underwent conventional MRI and diffusion-weighted imaging (DWI) at baseline and 1, 3, 6, and 18 months after the beginning of therapy. Tumor volumes and ADC values of ocular lesions were measured at each examination. Tumor volumes and mean ADC measurements of the five examination series were compared; correlation of ADC values and tumor regression was estimated. RESULTS: Mean ADC values of ocular melanomas significantly increased already 1 month after therapy whereas tumor volume significantly decreased only 6 months after therapy. Pretreatment ADC value of ocular melanomas and early change in ADC value 1 month after therapy significantly correlated with tumor regression. CONCLUSIONS: In ocular melanoma treated with PBT, ADC variations precede volume changes. Both pretreatment ADC and early change in ADC value may predict treatment response, thus expanding the role of DWI from diagnostic to prognostic.

Ultrahigh field magnetic resonance and colour Doppler real-time fusion imaging of the orbit--a hybrid tool for assessment of choroidal melanoma.

OBJECTIVES: A combination of magnetic resonance images with real-time high-resolution ultrasound known as fusion imaging may improve ophthalmologic examination. This study was undertaken to evaluate the feasibility of orbital high-field magnetic resonance and real-time colour Doppler ultrasound image fusion and navigation. METHODS: This case study, performed between April and June 2013, included one healthy man (age, 47 years) and two patients (one woman, 57 years; one man, 67 years) with choroidal melanomas. All cases underwent 7.0-T magnetic resonance imaging using a custom-made ocular imaging surface coil. The Digital Imaging and Communications in Medicine volume data set was then loaded into the ultrasound system for manual registration of the live ultrasound image and fusion imaging examination. RESULTS: Data registration, matching and then volume navigation were feasible in all cases. Fusion imaging provided real-time imaging capabilities and high tissue contrast of choroidal tumour and optic nerve. It also allowed adding a real-time colour Doppler signal on magnetic resonance images for assessment of vasculature of tumour and retrobulbar structures. CONCLUSIONS: The combination of orbital high-field magnetic resonance and colour Doppler ultrasound image fusion and navigation is feasible. Multimodal fusion imaging promises to foster assessment and monitoring of choroidal melanoma and optic nerve disorders. KEY POINTS: • Orbital magnetic resonance and colour Doppler ultrasound real-time fusion imaging is feasible • Fusion imaging combines the spatial and temporal resolution advantages of each modality • Magnetic resonance and ultrasound fusion imaging improves assessment of choroidal melanoma vascularisation.

The influence of silicone oil used in ophthalmology on the proton therapy of uveal melanomas.

In ocular proton therapy the important parameters range and modulation of the proton field are calculated by a simple geometric ray tracking. Due to the assumed homogeneous eye tissue, the relative-to-water proton stopping power is nearly constant within the radiation field. In cases when silicone oil tamponades are used, this will no longer hold. CT-data which are necessary to estimate the path length of protons within the oil show bigger attenuation of x-rays then in eye tissue. The use of a CT-calibration curve to deduce the relative-to-water electron density for proton stopping power calculation would be misleading giving a value of 1.05 and thus a higher proton stopping power. In reality the relative-to-water electron density is smaller, namely 0.95, leading to a proton range prolonged by about 11% of the path length within the silicone oil, if the demand for the range adjustment would not be recognized (missing information from ophthalmologists or no CT data). This finding is congruent in analytical and Monte Carlo calculations as well as in experimental investigations, being presented here. The misleading result of the CT calibration curve is explained and therapeutic consequences are demonstrated. Multiple Coulomb scattering in silicone oil does not affect the size of the planed irradiation field.

Small ciliary body tumors: ultrasound biomicroscopic assessment and follow-up of 42 patients.

PURPOSE: Detecting and following small tumors of the ciliary body is a particular challenge because of their location. Recently high-frequency ultrasound biomicroscopy (UBM) has been used to assist in this task. The aim of this study was to evaluate this subset of small ciliary body tumors through the use of UBM. DESIGN: Retrospective, noncomparative case series. METHODS: Forty-two patients with small ciliary body tumors (less than 4 mm) from our institution were included in the study with a median follow-up of 4.3 years. UBM was used to assess tumor characteristics including height, location, and internal and external features. The data were collected longitudinally, and statistical analysis was performed. RESULTS: Median initial tumor height was 2.05 mm (range 1.1 to 3.8 mm) as measured by UBM. By 5 years after diagnosis, five tumors (12%) exhibited growth. The overall mean growth rate was 0.026 mm per year (P = .00007). The most rapid period of growth was in the first year after diagnosis (growth rate 0.128 mm per year), after which the mean tumor size appeared to stabilize. CONCLUSIONS: UBM is a valuable tool for detecting and following small ciliary body tumors (less than 4 mm), as these lesions may go undetected by other methods. Despite the potential for local extension into the iris or choroid, few of the tumors in this study exhibited growth, suggesting that many of these tumors can be managed conservatively. UBM can be used to assess various internal tumor features; however, arriving at a specific diagnosis without histologic correlation is difficult.

CT-scan and intraocular tumours: detection and assessment of size and extrascleral growth of uveal melanomas.

Twenty-two patients, who were suspected of an intraocular tumour, were examined with the high resolution thin slice CT-scan (1.5 or 3 mm slices). The final diagnosis in 14 cases was an uveal melanoma, and in 3 cases in which an uveal melanoma was suspected a chorioretinal haemorrhage, an exudative macular degeneration type Junius Kuhnt and an intrascleral foreign body were respectively found. In 2 cases intraocular metastases were demonstrated, and in 2 other cases malignant lymphomata. One patient had a haemangioma. In 10 of the 14 patients with uveal melanomata enucleation was performed and 4 were treated by ruthenium application. The CT-scan was compared with ultrasonographic, operative and histological findings. From the study it appears that the CT-scan is useful for screening uveal melanomas. It is however difficult to distinguish the uveal melanoma from a secondary retinal detachment; differentiation from an exudative macular degeneration was not possible. The size of the tumour was only represented correctly on the CT-scan in half the cases. CT examination fails to demonstrate or exclude epi- and extrascleral growth. The multiple metastases and the haemangioma could only be seen with difficulty on the CT-scan; the latter was however clearly visible after the injection of contrast. The foreign body could be clearly seen without contrast.