Estimating uveal melanoma volume with ellipsoid tumour models.

Previous studies indicate that ocular blood flow is altered in eyes with choroidal melanoma. In the present study pulsatile ocular blood flow (POBF) was assessed to investigate whether there exists a correlation between tumour size and ocular blood flow parameters. Twenty-two patients with unilateral untreated choroidal melanoma were studied using two measurement techniques: POBF was measured with a pneumotonometer and local foveal fundus pulsation amplitude (FPA) by laser interferometry, and results were correlated. Tumour volume was calculated using the ellipsoidal solid model and was correlated to POBF and FPA. Levels of POBF and FPAs tended to be higher in tumour eyes compared with unaffected eyes, but the differences did not reach the level of significance. Both methods showed a high degree of correlation in unaffected eyes. In tumour eyes the correlation was slightly less pronounced. There was no correlation between tumour and POBF or FPA. Our results do not indicate choroidal hyperperfusion in patients with choroidal melanoma. The clinical usefulness of measuring POBF in tumour patients may be limited.

Correlation of fitzpatrick skin type and iris color with tumor size in 823 patients with uveal melanoma

Long-term results with linear accelerator LINAC-based stereotactic radiosurgery for intraocular uveal malignant melanoma were assessed. A retrospective study was carried out of patients with uveal melanoma after a 1-day session stereotactic radiosurgery at LINAC in Slovakia. In the period 2001-2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma, 11 ciliary body melanoma) was treated. The median tumor volume at baseline was 0.5 cm (with range from 0.2 to 1.6 cm). Tumors ranged in size from 2.4 to 20.8 mm in basal diameter and from 2.0 to 18.3 mm in thickness. The therapeutic dose was 35.0 Gy by 99% of dose volume histogram. Older age at treatment was correlated with the largest basal tumor diameter, tumor thickness, and TNM stage. The survival after stereotactic irradiation was 96% in 1 year, 93% in 2 years, 84% in 5 years, 80% in 7 years, and 53% in 11 years. In 20 (13.3%) patients, secondary enucleation was necessary because of complications (secondary glaucoma). Enucleation-free interval ranged from 1 to 6 years. The median age at death was lower (65.7 years) for patients who died from metastatic disease than for those who died from any other cause (75.0 years). Survival rates at 5-year intervals and the need for secondary enucleation because of complications after linear accelerator irradiation are comparable to other techniques.

Linear tumor size (T-size) estimated with conventional histology informs breast cancer management. Previously we demonstrated significant differences in margin and focality estimates using conventional histology versus digital whole-mount serial sections (WMSS). Using WMSS we can measure T-size or volume. Here, we compare WMSS T-size with volume, and with T-size measured conventionally. We also compare the ellipsoid model for calculating tumor volume to direct, WMSS measurement. Two pathologists contoured regions of invasive carcinoma and measured T-size from both WMSS and (simulated) conventional sections in 55 consecutive lumpectomy specimens. Volume was measured directly from the contours. Measurements were compared using the paired t-test or Spearman's rank-order correlation. A five-point 'border index' was devised and assigned to each case to parametrize tumor shape considering 'compactness' or cellularity. Tumor volumes calculated assuming ellipsoid geometry were compared with direct, WMSS measurements. WMSS reported significantly larger T-size than conventional histology in the majority of cases [61.8%, 34/55; means = (2.34cm; 1.99cm), p < 0.001], with a 16.4% (9/55) rate of 'upstaging'. The majority of discordances were due to undersampling. T-size and volume were strongly correlated (r = 0.838, p < 0.001). Significantly lower volume was obtained with WMSS versus ellipsoid modeling [means = (1.18cm3; 1.45cm3), p < 0.001]. Significantly larger T-size is measured with WMSS than conventionally, due primarily to undersampling in the latter. Volume and linear size are highly correlated. Diffuse tumors interspersed with normal or non-invasive elements may be sampled less extensively than more localized masses. The ellipsoid model overestimates tumor volume.

Uveal melanoma (UM) is the most frequent primary malignant intraocular tumor in adults with an estimated incidence of 4-5 per million per year in western countries [1]. About 50% of UM patients eventually develop metastasis. In a previous study, the prognosis of Chinese UM was mainly correlated with visual clinical features and gene sequencing results. Models designed to predict UM prognosis have been previously described [2], but these studies were based on Caucasians, not Chinese. Further, our previous study [3] determined that the clinical characteristics were different between Chinese and Caucasian UM patients. Therefore, in this study, we analyzed the clinical characteristics and survival status of 1553 patients diagnosed with UM over a period of 15 years in China, and also included factors that were not included in our previous study, such as the largest basal diameter, thickness, tumor size after updating the criteria, pigmentation, whether complicated with intraocular hemorrhage, ciliary body involvement, extraocular extension and TNM stage. We also constructed comprehensive prognostic models to predict the risk of metastasis within 2 years and death of UM after 2 years following treatment according to clinical characteristics using machine learning. The methods of this study are described in the Supplementary File. The clinical data of the UM patients are shown in Supplementary Table S1. The mean age of subjects was 47.2 ± 12.5 years (median, 48.0 years; range, 5-85 years), indicating that the onset age is much younger than Caucasians [4] for whom it usually occurs in the fifth to sixth decades. This demonstrates one of the racial variations of the disease. Nearly 70% of patients' visual acuity was worse than the 0.30 logarithm of the minimum angle of resolution (LogMAR). Intraocular pressure was within the normal range of 10-21 mmHg in 1279 (85.6%) patients, while it was lower than 10 mmHg in 148 (9.9%) patients and higher than 21 mmHg in 67 (4.5%) patients. The mean largest basal diameter was 12.0 ± 3.6 mm (median, 11.7 mm; range, 1.1-23.0 mm), and the mean tumor thickness was 7.1 ± 3.3 mm (median, 6.9 mm; range, 0.4-23.0 mm). According to the criteria of the American Joint Committee on Cancer classification (7th edition), there were 198 (12.9%) patients at Stage I, 1089 (71.1%) at Stage II, and 243 (15.8%) at Stage III. It was reported that the mixed cell-type tumor is the most common UM [5], but in the present study, the spindle cell-type UM was the most common pathological type (44.6%). The mean follow-up time was 49.5 ± 32.5 months (median, 43 months; range, 0-197 months). We followed 78.4% of patients for more than 2 years, 32.5% for more than 5 years and 3.2% for more than 10 years. The estimated 5-, 10-, and 15-year overall survival rates after treatment initiation were 84.0%, 72.0%, and 66.7% (Figure 1A). Shields et al [4] published a cohort study of 8100 UM patients, demonstrating UM-related survival rates of 91.4%, 86.5% and 83.8% and metastasis rates of 15%, 25% and 31%. Our 5-, 10- and 15-year UM-related survival rates were 85.6%, 75.5% and 69.5%, and were thus lower than Shields et al results [4]. However, the metastasis rates in our study were higher at 18.9%, 27.2% and 31.4% (Figure 1B). Similarly, our UM-related survival rates were lower than those reported in Scotland (92.3%, 87.4% and 83.8%) [6]. A total of 183 patients in our study died of UM metastasis, and the median duration from metastasis to death was 7 months. 75.5% of these patients died within 1 year of metastasis. A previous study showed that 80% of UM patients died within 1 year of metastasis and 92% within 2 years [7]. The most common site of metastasis observed was the liver (Supplementary Table S2). Multiple-site metastasis occurred in 70 patients. Survival analysis and predicting models of 1553 UM patients. A. Kaplan-Meier curve of overall survival. B. Kaplan-Meier curve of metastasis. C. ROC curve of model for predicting death after 2 years of treatment (UMDeath model). D. ROC curve of model for predicting metastasis within 2 years of treatment (UMMetastasis model). Abbreviations: UM, Uveal Melanoma; AUC, Area Under Curve; ROC, Receiver Operating Characteristic We assessed the variables with significant differences in univariate analysis for Cox multivariate regression analysis (Supplementary Table S3). There were few patients with known pathological types (n = 386), including spindle cell-type (n = 172), mixed cell-type (n = 131), and epithelioid cell-type (n = 83). Thus, pathological information was not included in the multivariate analysis. Using the log-rank test, we found that the prognosis of patients with epithelioid cell-type UM was significantly worse than spindle cell-type UM (Bonferroni corrected P < 0.001); which was consistent with another study [8]. Cox multivariate regression analysis of some other possible prognostic factors showed that older age, larger basal diameter and presence of subretinal fluid were associated with high mortality and metastasis, while hemisphere tumor was associated with better prognosis (Supplementary Figures S1 and S2). In addition, tumor pigmentation and position were only related to death (Supplementary Figure S1). We used random forest [9, 10] to construct two models (UMDeath and UMMetastasis): whether a patient will survive for more than 2 years after treatment and whether the tumor will metastasize within 2 years of treatment using demographic attributes, general ocular features and tumor-specific features, which are listed in Supplementary Table S3. The imbalanced ratio (the ratio between the numbers of majority samples and minority samples) was different when we chose a different censored time, and the ratio was abnormal when the censored time was 3 years. Thus, we chose to predict the prognosis of patients within 2 years. Moreover, four-fold cross-validation was used to fairly assess the performance of random forest, where the training dataset and the testing dataset are subject-independent (each sample was collected from one patient and all samples were split into training and testing datasets in cross-validation, therefore, one sample were used only once in the training or testing dataset). Also, 0.5 was selected as the threshold for both classification problems, on which all statistical results were based. Finally, we applied genetic feature selection to investigate which features were more related to the two classification problems (whether a patient would die after 2 years or have metastasis within 2 years after treatment) (Supplementary Material). When the model for the prediction of death was established, we found that the largest basal diameter, thickness, size, intraocular pressure and initial treatment were related to death. The boxplots show the results of four-fold cross-validation before and after feature selection (Supplementary Figure S3A and S3B). The sensitivity, specificity, accuracy, area under the curve (AUC) and their 95% confidence intervals are shown in Supplementary Table S4. PRiMeUM [2], a model for predicting the risk of metastatic UM, used the clinical characteristics and chromosomal information to determine the risk of metastasis within 2 years after the primary treatment; and showed that the accuracy of risk prediction could reach 83% using only clinical characteristics. Moreover, we established a model for predicting metastasis within 2 years after treatment. It was found that the largest basal diameter, size, stage, age, intraocular pressure and gender were associated with metastasis. The boxplots show four-fold cross-validation results before and after feature selection (Supplementary Figure S4A and S4B). The sensitivity, specificity, accuracy, AUC and their 95% confidence intervals are shown in Supplementary Table S5. Figures 1C and 1D, Supplementary Figures S3C and S4C depict the receiver operating characteristic and precision-recall curves of one-fold out of four-fold cross-validation for predicting death and metastasis, respectively. Two predictive models each found that intraocular pressure was an influencing factor for UM metastasis and death, and intraocular pressure and prognosis were related to tumor volume. The larger the tumor, the greater the impact on the eyeball structure and physiological conditions, and thus is more likely to cause changes in intraocular pressure. This present study is currently the largest retrospective study on UM in China. The age of onset for Chinese UM patients was earlier and the prognosis was worse than Western patients. The largest basal diameter and age were found to be related to prognosis in both statistical results and predictive models. Our predictive models found that intraocular pressure was related to both death and metastasis. These models achieved a high sensitivity and specificity for predicting survival and can predict metastasis to a certain extent. The authors thank those who participated in the present study. Supported by The Capital Health Research and Development of Special (2020-1-2052), Science & Technology Project of Beijing Municipal Science & Technology Commission (Z201100005520045, Z181100001818003), The Beijing Municipal Administration of Hospitals' Ascent Plan (DFL20150201), The National Natural Science Foundation of China (82101180), Beijing Natural Science Foundation (7204245), Scientific Research Common Program of Beijing Municipal Commission of Education (KM202010025018), Beijing Municipal Administration of Hospitals' Youth Programme (QMS20190203), Beijing Dongcheng District Outstanding Talents Cultivating Plan(2018). No conflicting relationship exists for any author. This research adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of Beijing Tongren Hospital. We obtained informed consent from all of these patients. YML, YL, and WBW contributed to the study conception. YNC, YNW and MXC designed the current study. HHZ, YNH, YF,YJL and JTL collected the data and implemented the follow-up. KZ, YNC and YNW performed the analyses and verified the underlying data. RTC, RF and HW arranged and checked the consistency of results. YNC and YNW wrote the initial draft of the manuscript. WBW and KZ commented on the manuscript and gave final approval of the version to be published. Written informed consent was obtained from the patients for participation in the study and publication of this article. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Correspondence and requests for materials and code should be addressed to WBW ([email protected]), YL ([email protected]) or YML ([email protected]). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Estimating Choroidal Melanoma Volume: Comparison of Methods

To evaluate the prognostic value of estimated tumour volume as a continuous biomarker in uveal melanoma and to compare its discriminative performance with the American Joint Committee on Cancer (AJCC) staging and multiplex ligation-dependent probe amplification (MLPA)-based genetic risk classification. This retrospective cohort study included consecutive patients with choroidal or ciliary body melanoma treated between 2016 and 2024 at a tertiary ocular oncology centre. Tumour volume (mm³) was calculated from baseline ultrasonography using an ellipsoidal (oval-base) approximation. The primary endpoint was metastasis-free survival (MFS). Survival was analysed using Kaplan-Meier methods and Cox regression. In the genetic subset, Firth-penalised Cox regression was applied. Prognostic discrimination was assessed using Harrell's concordance index (C-index) for AJCC stage, tumour volume, MLPA profile and combined models. A total of 237 patients were included (mean age 65.5±13.8 years; 54.0% female). Median follow-up was 61.0 months, and 64 patients developed metastasis during follow-up. Higher tumour volume was significantly associated with worse MFS, corresponding to an approximately 10% increase in hazard per 100 mm³ (HR 1.10; 95% CI 1.05 to 1.13; p<0.001). Continuous tumour volume showed higher discrimination than AJCC staging alone (C-index 0.73 vs 0.66). The highest discrimination was observed in models combining tumour volume and MLPA profile, with limited additional gain after including AJCC stage (C-index 0.79 in the MLPA subset). Continuous tumour volume provides more refined prognostic stratification in uveal melanoma and complements AJCC staging. Integrating volumetric, anatomic and molecular biomarkers improves risk assessment and may support individualised surveillance strategies.

Three-dimensional theoretical temperature distributions produced by 915 MHz dipole antenna arrays with varying insertion depths in muscle tissue

Maximal tumor diameter (MD) is traditionally an important prognostic factor in breast cancer. It must be questioned, however, how well a one-dimensional parameter alone can represent the actual morphologic condition of a three-dimensional body. Along with the pathologically assessed MD and two perpendicular diameters (PDs) of a lesion, eccentricity (EF) and the three-dimensional parameters tumor volume (TV) and surface area (TSA) of 395 ductal invasive breast carcinomas of limited size (10-40 mm) were calculated. The dependent prognostic variable was axillary lymph node involvement (ALNI). MD, TV and TSA area were highly significant predictors of ALNI; these variables had similar levels of prediction accuracy (univariate analyses: MD: P = 0.0003, TV: P = 0.0009, TSA: P < 0.0001; multivariate analyses: MD: P = 0.0018, TV: P = 0.0109, TSA: P = 0.0009; pseudo R-squared values: MD: 0.42, TV: 0.39, TSA: 0.39). Despite certain variations in tumor shape, TV and TSA with similar MD, there is no evidence that three-dimensional pathologic measurements (TV/TSA) are more precise prognostic predictors of ALNI compared to the one-dimensional measurement alone.

The management of localized choroidal melanoma generally involves definitive radiation therapy when globe preservation is feasible. Stereotactic radiosurgery (SRS) using the Gamma Knife system (Elekta AB, Stockholm, Sweden) or the CyberKnife system (Accuray Inc., Madison, WI, USA) is a well-established radiation modality for treating choroidal melanoma, with outcomes comparable to those of other radiation techniques. The ZAP-X Gyroscopic Radiosurgery system (ZAP Surgical Systems Inc., San Carlos, CA, USA) is a more recent platform designed for cranial SRS treatments. It may be considered a substitute for existing SRS modalities due to a similar dosimetric profile. Here, we report a case of choroidal melanoma treated using ZAP-X gyroscopic radiosurgery (GRS).A 46-year-old female presented with a medium-sized juxtapapillary choroidal melanoma in the left eye. The tumor was located nasal to the optic disc and involved the nasal half of the disc. On B-scan ultrasonography, the lesion measured 9.27 mm in its largest basal diameter and 5.55 mm in thickness. The gross tumor volume (GTV) was calculated at 0.391 cm³. A 1 mm isotropic margin was added to the GTV to account for setup errors, resulting in a planning target volume (PTV) of 0.878 cm³. A GRS treatment plan was developed using 12 isocenters to ensure adequate PTV coverage. A total of 286 non-coplanar beams were directed at the isocenter coordinates. A dose of 21 Gy in a single fraction was prescribed to the 54% isodose line at the PTV margin. Ocular akinesia was achieved using short-term general anesthesia. Treatment was delivered using the ZAP-X system, with a total treatment time of 59 minutes and 45 seconds. The delivered monitor units (MUs) totaled 23,339.47. The patient tolerated the procedure well, with no immediate post-treatment complications. Follow-up evaluations were conducted at six weeks and at three and a half months post-treatment. The patient reported no vision loss; however, fundus examination of the left eye at three and a half months revealed signs of macular edema. Regular ocular assessments and follow-up imaging are planned to monitor treatment response and evaluate long-term outcomes.This case report highlights ZAP-X as a potential alternative to established SRS modalities for the treatment of juxtapapillary choroidal melanoma. It also underscores the need for larger studies to evaluate the efficacy and safety of ZAP-X in the management of choroidal melanoma.

Uveal melanoma (UM) is the most common primary intra-ocular malignancy in adults (Singh et al. 2011). Gamma Knife radiosurgery (GKR) has been demonstrated to have similar outcomes as enucleation with less morbidity and is, therefore, utilized for the treatment of UMs (Koutsandrea et al. 2008; Lund 2013). Because some tumour margins are difficult to visualize with magnetic resonance imaging (MRI), this study utilized carbon fiducials for assistance with GKR treatment planning. To our knowledge, this is the first report of utilizing carbon fiducials to mark eye tumours for targeted radiotherapy. Two patients underwent this procedure. Case 1 is a 79-year-old man who was otherwise asymptomatic and noted to have a ciliochoroidal mass, T4bN0M0 (Fig. 1A–C) in the right eye during a Neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy in the left eye. His visual acuity was 20/25 on the right (OD), 20/20 on the left (OS); intra-ocular pressure (IOP) was 17 OD, 15 OS. The tumour measured 8.5 × 17.9 × 20.5 mm on ultrasound. Case 2 is a 69-year-old woman who presented with 6 weeks of decreased vision in the left eye (20/20 OD, 20/400 OS) with pressures of 19 OD, 16 OS. She was noted to have a large UM (T4cN0M0), (Fig. 1D–F) measuring 3.5 × 16.3 × 20.5 mm by ultrasound. Treatment options were discussed. Because of basal dimensions, plaque brachytherapy was not considered an option. Both patients had tumours incompletely visualized on MRI. Particularly, Case 2 (Fig. 1D) had infiltrative, thin edges and a retinal detachment that could not be well distinguished by MRI without fiducials. Both patients elected to undergo fiducial placement and GKR. Fiducials were placed in the operating room. A 360-degree conjunctival peritomy preceded tagging of rectus muscles with silk sutures. Sclera was inspected for evidence of extrascleral tumour extension. Transillumination and indirect ophthalmoscopy were utilized to mark the gross tumour volume (GTV). Three BioMARC fiducials 1 mm × 5 mm (Carbon Medical Technologies, Saint Paul, MN, USA), composed of carbon-coated zirconium for biocompatibility, with preplaced double-armed 5-0 nylon sutures (Fig. 1G), were secured 2 mm beyond the border of the GTV. Conjunctiva was closed. Patients were treated with subconjunctival Ancef, Decadron, and discharged with atropine and Blephamide. Five days after fiducial placement, patients underwent GKR. Retrobulbar block was performed with 2% lidocaine, bupivacaine and hyaluronidase. Leksell stereotactic head frame was applied. Magnetic resonance imaging (MRI) orbits with contrast were repeated and imported into the treatment planning system Leksell GammaPlan, Elekta AB, Stockholm, Sweden. The clinical target volume (CTV), determined by the GTV plus 2 mm delineated by the fiducials, was treated. Patients were discharged the same day. Case 1 was treated with 11 isocenters to a CTV of 3010 mm3, 25 Gy to the 50% isodose line, maximum dose of 50 Gy. Case 2 was treated with 11 isocenters to a CTV of 2680 mm3, 27 Gy to the 50% isodose line, maximum dose of 54 Gy. At 4.8 months postradiosurgery, Case 1 had decreased visual acuity (20/60) and tumour thickness (8.1–8.2 mm) by ultrasound (Fig. 1H). After 3.4 months, Case 2 had improved visual acuity (20/125) and tumour volume (2.9 × 15.1 × 16.6 mm) by ultrasound (Fig. 1I). Notably, one of three fiducials (the most anterior fiducial) for Case 1 demonstrated extrusion at 4.8 months and was surgically removed. In summary, we present two patients with large UMs who were managed with GKR after fiducial placement. This approach may be beneficial for patients whose tumours are difficult to visualize on MRI. It may also be worthwhile to compare the tantalum fiducials currently used for proton beam radiotherapy (PBT) to mark UMs (Gragoudas et al. 1977) with carbon fiducials.

To describe time trends, from 1987 through 1997, (1) in size of choroidal melanoma among patients with recent diagnosis confirmed at a clinical center that participated in the Collaborative Ocular Melanoma Study (COMS) and (2) in choice of treatment by patients who did not enroll in one of the COMS randomized trials. Investigators at all COMS clinical centers (41 in the United States and 2 in Canada) agreed to report, in a masked fashion that did not include personal identifiers, all patients diagnosed as having choroidal melanoma during the accrual period for COMS randomized trials of radiotherapy. Information reported for patients who did not enroll in a COMS randomized trial included tumor dimensions, date of diagnosis, and initial treatment selected. Patients reported by centers that continued to report cases until 1997 and diagnosed as having choroidal melanoma no more than 1 year before evaluation at a participating COMS center contributed the data analyzed. Time trends in tumor size among patients reported and in elective treatment of patients not enrolled in COMS randomized trials. Of 8712 patients with choroidal melanoma examined, 6703 met criteria for analysis of time trend in tumor size and 4077 were analyzed for treatment trends over time. The number of cases with longest tumor basal diameter greater than 15.0 mm declined over time from 393 (30%) of 1330 cases reported in 1987 through 1989 to 345 (25%) of 1397 cases reported in 1996 or 1997. The proportion of patients eligible for COMS randomized trials who did not enroll and who elected enucleation remained stable over time for tumors of all sizes; the proportion of these patients who elected eye-conserving radiotherapy increased over time. Juxtapapillary tumors accounted for nearly half of the enucleations among ineligible patients who had tumors no larger than 15.0 mm in longest basal diameter. Among patients examined at COMS centers during 1987 through 1997, the trends observed for patients with recently diagnosed choroidal melanoma included increasing presentation with tumors of smaller size, decreasing use of enucleation for choroidal melanoma 15.0 mm or less in longest basal diameter, and increasing use of such strategies for larger tumors.

Purpose Uveal melanoma is the most common primary intraocular tumour in adults. There is no standard adjuvant treatment to prevent metastasis and no effective therapy in the metastatic setting. (−)-4-O-(4-O-β-D-glucopyranosylcaffeoyl) quinic acid (QA) is a new compound isolated from the endophytic fungus Penicillium sp.FJ-1 of Avicennia marina, with potent activities to inhibit the PI3K. Our work further investigated effects of QA against uveal melanoma and explored its underlying mechanisms. Methods MP65 cells were treated with QA at different concentrations. CCK-8 assay was used to detect effects of QA on cell viability. PI staining was used to detect cell cycle arrest. Tumour model was established by injecting MP65 cells into nude mice subcutaneously. Tumour-bearing mice were divided into three groups (5 mice per group). Mice were treated with QA (5 or 10 mg/kg) or saline by intraperitoneal injection five times per week. RT-qPCR and western blot were used to detect the expression of genes and proteins, respectively. Results QA significantly inhibited the proliferation of uveal melanoma cells and induced the cell cycle arrest as well as autophagy. Moreover, QA treatment significantly slowed tumour growth of uveal melanoma, shown by decreased tumour volume and weight. Furthermore, QA treatment markedly decreased the protein expression of p-PI3K and p-AKT in tumour tissues. Conclusions Our data provided scientific rationale to develop QA as a promising anti-tumour agent against uveal melanoma.

To evaluate whether intraprocedural 3D quantification of Lipiodol deposition on cone-beam computed tomography (CBCT) can predict tumor response on follow-up contrast-enhanced magnetic resonance imaging (CE-MRI) in patients with hepatocellular carcinoma (HCC) treated with conventional transarterial chemoembolization (cTACE). This IRB approved, retrospective analysis included 36 patients with 51 HCC target lesions, who underwent cTACE with CBCT. CE-MRI was acquired at baseline and 1 month after cTACE. Overall tumor volumes as well as intratumoral Lipiodol volumes on CBCT were measured and compared with the overall and necrotic (non-enhancing) tumor volumes on CE-MRI using the paired student's t test. Tumor response on CE-MRI was assessed using modified response evaluation criteria in solid tumors (mRECIST). A linear regression model was used to correlate tumor volumes, Lipiodol volumes, and the percentage of Lipiodol deposition on CBCT with the corresponding parameters on CE-MRI. Nonparametric spearman rank-order correlation and trend test were used to correlate the percentage of Lipiodol deposition in the tumor with tumor response. A strong correlation between overall tumor volumes on CBCT and CE-MRI was observed (R(2) = 0.986). In addition, a strong correlation was obtained between the volume of Lipiodol deposition on CBCT and tumor necrosis (in cm(3)) on CE-MRI (R(2) = 0.960), and between the percentage of Lipiodol deposition and tumor necrosis (R(2) = 0.979). Importantly, the extent of Lipiodol deposition (in percentage of total tumor volume) correlated strongly with tumor response on CE-MRI (Spearman rho = 0.84, p < 0.001). Intraprocedural 3D quantification of Lipiodol deposition on CBCT can be used to predict tumor response on follow-up CE-MRI.

Evaluation of blood supply to choroidal melanoma based on comparison of Doppler characteristics of blood flow with angiographic variant of angioarchitectonics and densitometric parameters of the tumor. The study was performed in 135 patients (135 eyes) with choroidal melanoma. The initial prominence of the tumors varied from 0.6 to 15.2 mm (mean 5.07±3.58 mm), the diameter of the tumor base varied from 4.1 to 22 mm (mean 10.97±3.62 mm). Taking into account the biometric characteristics of choroidal melanoma, all patients were divided into 3 groups: «small» (n=49), «medium» (n=34) and «large» (n=52). In addition to standard diagnostic examination, the following instrumental methods for assessing the blood supply of choroidal melanoma were carried out: angiography with indocyanine green, optical coherence tomography angiography, ultrasound in color Doppler mapping mode, ultrasound histography. Comparative analysis of Doppler ultrasound and contrast angiography data in assessing the blood supply of choroidal melanoma established that the first angiographic type, presented by straight and parallel vessels (65%, p=0.037), is characteristic for hypovascular and avascular masses, the second type - for hypervascular choroidal melanomas, in which the new vessels can take the form of arches, loops and nets (68%, p=0.027). The study of densitometric characteristics in choroidal melanoma of various sizes indicates a natural decrease in the acoustic density of the tumor tissue with increase in the prominence of the mass, while there are significant differences in the acoustic density values in hypo/avascular (36.53±5.37 dB) and hypervascular variants (29.28±4.53 dB) of blood supply to tumor tissue. The obtained data on acoustic density of choroidal melanoma can be used in clinical practice for indirect assessment of the nature of blood supply to choroidal melanoma.