Diagnosis Of Uveal Melanoma Research Articles

Intravitreal anti-VEGF therapy for macular radiation retinopathy: a 10-year study.

To report long-term experience with intravitreal anti-vascular endothelial growth factor treatment for radiation maculopathy. From 2005-2015, 120 consecutive patients underwent intravitreal anti-VEGF therapy for radiation maculopathy. Inclusion criteria included a diagnosis of uveal melanoma treated with plaque radiotherapy and subsequent macular radiation vasculopathy (exudate, retinal hemorrhage, intraretinal microangiopathy, neovascularization, edema). Anti-VEGF therapy involved continuous injections in 4- to 12-week intervals with doses of 1.25 mg/0.05 mL, 2.0 mg/0.08 mL, 2.5 mg/0.1 mL, or 3.0 mg/0.12 mL of bevacizumab as well as 0.5 mg/0.05 mL or 2.0 mg/0.05 mL of ranibizumab. Goals were maintenance of visual acuity and normative macular anatomy. Safety and tolerability (retinal detachment, hemorrhage, infection), visual acuity, central foveal thickness on optical coherence tomography imaging, and clinical features of radiation maculopathy were analyzed. Progressive reductions in macular edema, hemorrhages, exudates, cotton-wool spots, and microangiopathy were noted. At last follow-up, 80% remained within 2 lines of their initial visual acuity or better, with a mean treatment interval of 38 months (range 6-108 months). Kaplan-Meier analysis of the probability of remaining within 2 lines of initial visual acuity was 69% at 5 years and 38% at 8 years of anti-VEGF therapy. Discontinuation of therapy was rare. Relatively few acute or long-term side effects were noted, allowing for good long-term patient accrual. Continuous intravitreal anti-VEGF therapy in patients with radiation maculopathy was well-tolerated and preserved vision. In most cases, reductions or resolution of retinal hemorrhages, cotton-wool spots, and retinal edema were noted for up to 10 years.

Diagnostic value of SOX-10 immunohistochemical staining for the detection of uveal melanoma.

ObjectivesSOX-10 has been shown to be a sensitive marker of cutaneous melanoma. This study aimed to evaluate Sox-10 expression in uveal melanoma.MethodsA total of 40 tissue blocks of enucleated eyes with uveal melanoma were cut and stained using an anti-SOX-10 mouse monoclonal antibody and HMB-45 antibody.ResultsSOX-10 showed exclusive nuclear positivity in 100% of the uveal melanoma cases (38/38). HMB-45 showed cytoplasmic positivity in 97.3 (37/38). Positivity for SOX-10 was also noted in the inner and outer nuclear layers of the retina in 78% of the enucleated eyes.ConclusionsSOX-10 expression proved to be the most sensitive marker for uveal melanoma, and therefore, we propose a modified panel for the diagnosis of uveal melanoma that includes both SOX-10 and HMB-45. The observation of distinct, diffuse nuclear SOX-10 expression in retinal inner and outer nuclear layers is a finding that warrants further investigation as a marker for retinoblastoma.

Fine-needle aspiration biopsy of uveal melanoma: outcomes and complications

PurposeTo report outcomes and complications of fine-needle aspiration biopsy (FNAB) of uveal melanoma performed for diagnostic and prognostic purposes.MethodsProspective interventional case series of 150 consecutive patients with a clinical diagnosis...

Diagnostic Cytologic Features of Uveal Melanoma

To report the cytologic characteristics of uveal melanoma. This is a prospective, single-center study of consecutive patients. All patients with a clinical diagnosis of uveal melanoma from May 2009 to July 2013 who underwent prognostication fine-needle aspiration biopsy (FNAB) were included. The cytologic characteristics of uveal melanoma were analyzed for 150 consecutive patients with a clinical diagnosis of uveal melanoma who were treated at the Cleveland Clinic Cole Eye Institute between May 2009 and August2012. Cellular features of all cases were analyzed for cell type, presence of melanin, nuclear grade, tumor-infiltrating lymphocytes, and necrosis. Cytology was then correlated with histopathology in enucleated eyes. A total of 150 patients were included. Seven samples of tumor resections were excluded from the study because they were studied by impression smears. A total of 143 FNAB samples of 143 patients formed the basis for analysis. Fifty-three percent of the patients were male, and the average age for all patients was 60 years. Transcorneal (n = 8), transscleral (n = 71), and transvitreal (n = 64) approaches were used. Of 143 samples, 131 were adequate. Among these, spindle cells were observed in 98% (63% mixed and 35% spindle only), whereas only epithelioid cells were observed in 2 samples. Melanin granules were observed in 80% of samples. Tumor nuclear grade (atypia) increased with tumor height and by tumor location (least atypia with iris tumors). Cytologic features such as spindle cells and melanin granules, present in 98% and 80% of samples, respectively, are important cytologic diagnostic features. Tumor nuclear grade (atypia) increased with tumor height. Iris melanoma has bland features compared with ciliary and choroidal melanoma.

International Validation of the American Joint Committee on Cancer's 7th Edition Classification of Uveal Melanoma.

Although an accurate uveal melanoma staging system is needed to improve research and patient care, the evaluation of eye cancer staging systems requires international multicenter data sharing to acquire a statistically significant analysis. To assess patient mortality outcomes associated with uveal melanoma staging according to the 7th edition of the American Joint Committee on Cancer's AJCC Cancer Staging Manual. A committee was formed to create patient-specific data fields for patients with uveal melanoma. Ten subspecialty ophthalmic oncology centers from 4 continents shared data. Patient selection criteria included diagnosis of uveal melanoma from April 1, 2001, to April 1, 2011, adequate records to allow tumor staging by the AJCC criteria, and follow-up for metastatic melanoma. Primary treatments included local resection, radiation therapy, and enucleation. Metastasis after initial tumor staging with 5- and 10-year Kaplan-Meier metastasis-free point estimates, depending on AJCC prognostic stages I through IV, tumor size category, and subclassification (defined by the presence of ciliary body involvement and/or extrascleral extension). A total of 3809 patients were entered into the database. Of these, 3377 records (88.7%) were complete. Primary ciliary body and choroidal melanoma was the diagnosis for 3217, and 160 had primary iris melanoma. Tumor size categories were T1 in 1115 (34.7%) of the 3217 patients, T2 in 1128 patients (35.1%), T3 in 789 patients (24.5%), and T4 in 185 patients (5.8%). The 5- and 10-year Kaplan-Meier metastasis-free point estimates by tumor size categories were 97% (95% CI, 95%-98%) and 94% (95% CI, 91%-96%) for T1 tumors, 85% (95% CI, 82%-88%) and 80% (95% CI, 75%-84%) for T2 tumors, 77% (95% CI, 73%-80%) and 68% (95% CI, 60%-74%) for T3 tumors, and 61% (95% CI, 49%-71%) (5-year only) for T4 tumors, respectively. Increasing tumor size was consistent with increased metastasis risk (P <.001). Subclassifications were significantly associated with increased risk of metastasis (P < .001). The AJCC prognostic and anatomical groupings were as follows: stage I, 1030 (32.0%); stage IIA, 1095 (34.0%); stage IIB, 710 (22.1%); stage IIIA, 282 (8.8%); stage IIIB, 79 (2.5%); and stage IIIC, 21 (0.7%). The 5- and 10-year Kaplan-Meier metastasis-free estimates for prognostic stages were 97% (95% CI, 95%-98%) and 94% (95% CI, 91%-96%) for stage I, 89% (95% CI, 86%-91%) and 84% (95% CI, 80%-88%) for stage IIA, 79% (95% CI, 75%-83%) and 70% (95% CI, 62%-76%) for stage IIB, 67% (95% CI, 59%-73%) and 60% (95% CI, 51%-68%) for stage IIIA, 50% (95% CI, 33%-65%) and 50% (95% CI, 33%-65%) for stage IIIB, and 25% (95% CI, 4%-53%) (5-year only) for stage IIIC, respectively. The 160 iris melanomas were too few for subgroup analysis. Multicenter, worldwide, Internet-based data sharing was used to study a heterogenous patient population in ophthalmic oncology. Our results support the continued use of the 7th edition of the AJCCCancer Staging Manual for uveal melanoma.

Development and external validation of a prognostic nomogram for metastatic uveal melanoma.

BackgroundApproximately 50% of patients with uveal melanoma (UM) will develop metastatic disease, usually involving the liver. The outcome of metastatic UM (mUM) is generally poor and no standard therapy has been established. Additionally, clinicians lack a validated prognostic tool to evaluate these patients. The aim of this work was to develop a reliable prognostic nomogram for clinicians.Patients and MethodsTwo cohorts of mUM patients, from Veneto Oncology Institute (IOV) (N=152) and Mayo Clinic (MC) (N=102), were analyzed to develop and externally validate, a prognostic nomogram.ResultsThe median survival of mUM was 17.2 months in the IOV cohort and 19.7 in the MC cohort. Percentage of liver involvement (HR 1.6), elevated levels of serum LDH (HR 1.6), and a WHO performance status=1 (HR 1.5) or 2–3 (HR 4.6) were associated with worse prognosis. Longer disease-free interval from diagnosis of UM to that of mUM conferred a survival advantage (HR 0.9). The nomogram had a concordance probability of 0.75 (SE .006) in the development dataset (IOV), and 0.80 (SE .009) in the external validation (MC). Nomogram predictions were well calibrated.ConclusionsThe nomogram, which includes percentage of liver involvement, LDH levels, WHO performance status and disease free-interval accurately predicts the prognosis of mUM and could be useful for decision-making and risk stratification for clinical trials.

Clinical Presentation, Pathological Features and Natural Course of Metastatic Uveal Melanoma, an Orphan and Commonly Fatal Disease

Background: Uveal melanoma (UM) is a rare disease characterized by an unpredictable course and a variable outcome. We assessed the natural course of patients with metastatic uveal melanoma (MUM). Methods: Data from 76 patients with MUM who were treated in Leuven between 1957 and 2008 were examined retrospectively. Statistical analysis involved the nonparametric, Kaplan-Meier and log rank tests. Results: The median age at diagnosis of UM was 58 years (range 30-94). Synchronous metastases were found in 9% of the cases; all other patients had metachronous disease after a median interval of 40 months (range 7-420). Statistical analysis failed to identify factors related to the time until metastatic spread with the exception of a significant negative correlation with age at UM diagnosis (Spearman: ρ = -0.4, p < 0.001). The most frequent metastatic site was the liver (in 96% of the patients). The median time from diagnosis of UM until death was 47 months (range 2-236) and only 5 months in patients with metastatic disease (range 1-128). Conclusions: MUM is an orphan disease. Advances in MUM can only be achieved by the networking of sites interested in this rare tumor type, with systematic collection of data and tumor tissue for improving our understanding of the molecular biology of this disease.

Assessment of the effect of iris colour and having children on 5-year risk of death after diagnosis of uveal melanoma: a follow-up study

BackgroundTo examine the all-cause mortality and uveal melanoma specific mortality among newly diagnosed uveal melanoma patients after five years. Furthermore, we assess of the effect of iris colour and having children on 5-year risk of death after diagnosis of uveal melanoma. Therefore, we assess the performance of an individual prediction model of survival from uveal melanoma.MethodsA cohort of 459 patients aged 45 to 79 years with newly diagnosed uveal melanoma was recruited between 2002 and 2004 from the Division of Ophthalmology, University of Essen, Germany. Survival probabilities were estimated by Kaplan-Meier survival analysis. The clinical and histopathological characteristics were obtained from medical records. Iris colour and childbearing history were assessed at baseline by a computer-assisted telephone interview. We used crude and multivariable Cox proportional hazards regression to estimate unadjusted and adjusted hazard ratios (HR) and corresponding 95% confidence intervals (95%CIs) with respect to death from uveal melanoma and death from all causes. We used the Cox model to estimate adjusted probabilities of primary events. For computing Harrell’s C statistics, we used a Cox model including the prognostics factors gender, age at diagnosis, ciliary body involvement, largest basal tumour diameter, and iris colour.ResultsThe 5-year uveal melanoma-specific survival probability was 82.9% (95% CI: 79.1-86.3). Main prognostic factors for the death of uveal melanoma were ciliary body involvement (HR: 1.7 (95% CI:1.0-2.8)), largest basal tumour diameter >15 mm HR: 7.0 (95% CI: 3.5-13.9), light iris colour (HR: 2.3 (95% CI: 0.9-5.8), having children (HR: 0.6 (95% CI: 0.2 - 1.7)), and gender (HR: 0.7 (95% CI: 0.4-1.1)). The value of the bootstrap-corrected C statistics was 0.76 (95% CI: 0.74-0.77).ConclusionBeyond the established prognostic factors, light iris colour also appears to be a prognostic factor for death from uveal melanoma.

Treatment of liver metastases from uveal melanoma: a retrospective single-center analysis

Metastatic liver melanoma is a rare event in the Chinese population with extremely poor prognosis. Any treatment that controls a metastatic hepatic lesion potentially prolongs survival. This study aimed to evaluate the survival of patients with isolated liver metastases from uveal melanoma treated with partial hepatectomy or non-surgical management and to find the best therapeutic modality for these patients. From January 1996 to September 2008, eight patients with liver metastases secondary to uveal melanoma were admitted to our hospital. Five patients underwent partial hepatectomy and 3 received other treatments (TACE, RFA, PEI). Their medical records were reviewed and overall survival was analyzed. The patients comprised 3 men and 5 women, with a median age of 44 years. Six patients presented with liver metastases at the time the primary tumor was diagnosed. The interval from the diagnosis of uveal melanoma to liver metastasis in the remaining 2 patients was 9.5 and 32.5 months, respectively. The median survival after the treatment of liver metastasis was 11.5 and 7.5 months in the surgical and non-surgical groups, respectively. There was no procedure-related mortality in the whole study cohort. Partial hepatectomy or other therapies were safe and feasible for isolated liver metastases from uveal melanoma. Aggressive treatment with multidisciplinary modalities may result in prolonged survival.

Malignant melanoma of the uvea: Diagnosis, characterization and prognosis

AbstractPurpose: To summarize available data on uveal melanoma biology, diagnosis and clinical characterization. Methods: Herein, we review diagnostic criteria, clinical characterization and therapeutic implications of the emerging molecular biology in posterior uveal melanoma/high risk indeterminate choroidal pigmented lesion. Results: The diagnosis of uveal melanoma is based on clinical examination with indirect ophthalmoscope and ultrasonograpy. The use of mnemonic "to find small ocular melanoma" is useful in risk stratification of small indeterminate melanocytic choroidal lesions. The use of optical choerence tomograpy and autofluorescence also help in identifying sub‐retinal fluid and orange pigment. In the cytogenetic era, tumor‐sampling procedures are becoming the main prognostic tools for uveal melanoma patients. Conclusions: Ophthalmic oncology is moving in the same direction as all other oncologic subspecialties, starting to determine the patient’s risk using sampling‐based laboratory techniques. However, it is essential to start treating patients earlier (in the premalignant tumor stage) and to develop consistent, selective and effective adjuvant therapy

Management of Occult Necrotic Melanomas

A smanyas20%ofuvealmelanoma–containingeyeshistorically had opaquemedia andmore than half of such tumors were unsuspected.1,2 While many ophthalmic oncologic centers, including ours, have more than 99% accuracy of uvealmelanoma diagnosis, in eyeswith opaquemedia andextensivenecrosis the correctdiagnosis can sometimesbe impossible to establish with ultrasonography, magnetic resonance imaging (MRI), and fine-needle aspiration biopsy (FNAB).3,4 We present 5 cases that illustrate these problems.

Development of renal cell carcinoma in patients with primary uveal melanoma.

e15563 Background: Somatic mutations of BRCA1 associated protein1 (BAP1), a tumor suppressor gene, located on chromosome 3p21.1 is found in 50% of primary uveal melanoma (UM) and has been linked to an aggressive phenotype. It is recently reported that somatic BAP1 mutation is also found in 15% of renal cell carcinomas (RCC). We hypothesize that germ line or somatic mutation of BAP1 may contribute the carcinogenesis of patients (pts) who have both UM and RCC. Methods: Retrospective chart review on patients with primary UM treated at Wills Eye Institute and Thomas Jefferson University between 1997 and 2012 revealed 15 patients with both UM and histologically proven RCC. Clinical information on these patients was analyzed. Tumor tissue and blood specimens were also collected for BAP1 gene mutation analysis. Results: Of the 15 patients, 12 (80%) were males. Median age at diagnosis of UM was 57 years old. Six of these patients developed liver metastasis on follow-up (40%). From 8 patients whose pathology data on RCC were available, 6 of them were clear cell type (75%), one was papillary type-1 and one was multilocular cystic subtype. The diagnosis of RCC proceeded the UM diagnosis in 5 of 15 patients, while the diagnoses were made concurrently in 4 patients. Six patients were diagnosed with UM first. For pts who had genetic testing on UM, chromosome 3 abnormalities are the most common abnormalities found. Peripheral blood specimens were tested for 2 patients and germ-line BAP1 mutation was not discovered. Detailed tumor tissue BAP1 mutation analysis is ongoing. Conclusions: The development of RCC is relative common for UM and the molecular mechanism is being determined. It is male dominant in sex and mostly clear cell type in histology of RCC. Further gene mutation analysis and its association with clinical data will be reported.

Pathology and genetics of uveal melanoma

Uveal melanoma is the most common malignant tumour of the adult eye. Around half of all uveal melanoma patients will eventually die of their disease. There are a number of effective options to treat the primary tumour locally, but once the tumour has metastasised, there are no curative therapies. Traditionally, the diagnosis of uveal melanoma and prognostic prediction was based solely on the clinical presentation and detailed histopathological evaluation. Recent genetic findings have shed light on the biology of these tumours, and led to the development of genetic tests that can help assess their malignant potential and prognosis. The genes, proteins and pathways that have been (and continue to be) discovered will likely result in novel targeted therapeutic approaches with high efficacy and low toxicity. In this review, we summarise the clinical, pathological and genetic features of uveal melanoma, with emphasis on recent discoveries.

Translation and validation of the Polish version of the EORTC QLQ-OPT30 module for the assessment of health-related quality of life in patients with uveal melanoma

The purpose of this study was to translate into Polish and validate the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Ophthalmic Module (QLQ-OPT30). The QLQ-OPT30 was translated and pilot-tested according to EORTC guidelines. Patients were qualified based on the histological or ophthalmoscopic and ultrasonographic diagnosis of uveal melanoma. Each patient filled out the Polish version of the EORTC Quality of Life Questionnaire (EORTC QLQ-C30), the QLQ-OPT30 module and a personal questionnaire. Patients were divided into three groups according to treatment type, melanoma localisation and possible negative outcomes of the disease or treatment. Reliability and validity test were performed and patients' comments were analysed. Our study included 94 patients--50 women (53.2%) and 44 men (46.8%) in the mean age of 58.4 (±13) years. Treatment type and melanoma location did not influence the health-related quality of life. The QLQ-OPT30, apart from two scales, showed positive internal consistency (Cronbach's alpha coefficients range: 0.70-0.88). We found the Polish version of the EORTC QLQ-OPT30 module a useful tool for measuring health-related quality of life in uveal melanoma patients. Although its discriminative validity is somewhat limited it still can be recommended for clinical use in the Polish population.

Malignant melanoma of the uvea: diagnosis, characterization and prognosis

AbstractPurpose To summarize available data on uveal melanoma biology, diagnosis and clinical characterization.Methods Herein, we review diagnostic criteria, clinical characterization and therapeutic implications of the emerging molecular biology in posterior uveal melanoma/high risk indeterminate choroidal pigmented lesion.Results The diagnosis of uveal melanoma is based on clinical examination with indirect ophthalmoscope and ultrasonograpy. The use of mnemonic "to find small ocular melanoma" is useful in risk stratification of small indeterminate melanocytic choroidal lesions. The use of optical choerence tomograpy and autofluorescence also help in identifying sub‐retinal fluid and orange pigment. In the cytogenetic era, tumor‐sampling procedures are becoming the main prognostic tools for uveal melanoma patients.Conclusion Ophthalmic oncology is moving in the same direction as all other oncologic subspecialties, starting to determine the patient’s risk using sampling‐based laboratory techniques. However, it is essential to start treating patients earlier (in the premalignant tumor stage) and to develop consistent, selective and effective adjuvant therapy

Disseminated tumour cells in bone marrow of patients with uveal melanoma

Approximately 50% of patients with uveal melanomas develop metastases. Thus, it is important to improve our understanding of how melanoma metastases develop. As part of a uveal melanoma micrometastasis study, we compared the detection rates of immunomagnetically selected (IMS) tumour cells in bone marrow (BM) with positively stained tumour cells using immunocytochemistry (ICC). Bone marrow mononuclear cells were isolated. Immunocytochemistry cytospin preparations were immunocytochemically stained in parallel with two different melanoma antibodies, 9.2.27 and HMB45. Using IMS, melanoma cells were selected from BM mononuclear cell fractions using immunomagnetic beads coated with the 9.2.27 antibody and identified by light microscopy. In cytospin preparations from 226 patients, melanoma cells were detected in 24 (10.6%), 10 with 9.2.27 and 17 with the HMB45 antibody. In three cases, we found positive cells with both antibodies. Six of the 226 (2.6%) patients that stained positively with ICC died with metastatic disease, all also positive with IMS. Sixty-six (29.2%) patients had positive BM samples with IMS at the first examination. Immunomagnetic selection (IMS) was positive in 36.8% of the 57 patients who later developed clinical metastases. Twenty-one IMS-positive patients and 31 IMS-negative patients died of metastases, in total 52 of 226 patients (23.0%). The mortality rate of melanoma metastasis was 24% (6/24) after at least 4 ½ years in ICC-positive patients compared to 38.5% (20/52) in IMS-positive patients. The presence of melanoma cells in BM of patients with uveal melanoma is documented in our study with IMS and ICC. Immunomagnetically selected is more sensitive than ICC in detecting tumour cells in BM. However, statistically, we did not find any prognostic impact of the presence of melanoma cells in BM.

Episcleral brachytherapy for uveal melanoma: analysis of 136 cases

To assess the results of I-125 episcleral brachytherapy (EB) in uveal melanoma: tumour control, visual acuity (VA), eye preservation and survival. Prospective and consecutive study of patients with a diagnosis of uveal melanoma at the Ocular Oncology Unit in the Valladolid University Teaching Hospital treated with EB between September 1997 and June 2008. Ocular examination and extraocular and systemic extension data were registered in a database at the time of the diagnosis and during the follow-up. Among a total of 310 patients diagnosed between September 1997 and June 2008, 136 were treated with EB (mean age, 58.3). Mean follow-up was 55.3 months. As for tumour type, 66.9% were nodular and 39% mushroom shaped. With respect to size, 80.9% were medium, 7.4% small and 11.8% large. After 4.6 years of follow-up, tumours were controlled in 97.1%, with a 55.1% reduction in mean height; only 2.9% of patients showed recurrence. VA was maintained in 16.2% of patients and 17.6% showed an increase; 33% had retinopathy and 14.6% optic neuropathy. Only 5.1% of patients underwent enucleation due to complications and there has been 1 melanoma-related death to date. I-125 EB is effective in tumour control, allowing preservation of the eye and useful visual function for the majority of patients.

Influence of Age on Prognosis of Young Patients with Uveal Melanoma: A Matched Retrospective Cohort Study

To determine the influence of patient age on life prognosis in patients with uveal melanoma. Matched retrospective cohort study of 122 patients in each age category (young [≤20 years], mid-adults [21-60 years], older adults [>60 years]). Kaplan-Meier estimates of tumor-related metastasis at 3, 5, and 10 years were 1%, 8%, and 8% in young; 8%, 11%, and 26% in mid-adults; and 13%, 16%, and 24% in older adults. After exclusion of iris melanoma, Kaplan-Meier estimates of tumor-related metastasis at 3, 5, and 10 years were 2%, 11%, and 18% in young; 9%, 14%, and 21% in mid-adults; and 9%, 34%, and 33% in older adults. Risk factors for metastasis based on multivariate analysis included increasing age in young (p=0.05, hazard ratio [HR] 1.33), male gender in mid-adults (p=0.046, HR 4.23), and larger tumor basal diameter in mid-adults (p=0.002, HR 1.37) and older adults (p=0.001, HR 1.30). After adjusting for tumor diameter, the metastatic rate was lower in young patients compared to mid-adults (0=0.042, HR 3.00) and older adults (p=0.007, HR 4.20). Younger patient age at the time of diagnosis of uveal melanoma is associated with lower rate of metastasis compared to mid-adults and older adults.

Imaging Modalities for Uveal Melanoma

Purpose:To review the spectrum of imaging modalities commonly used in clinical practice for the diagnosis and management of uveal melanoma.Materials and Methods:Review of literature.Results:Various forms of ophthalmic imaging are useful in the characterisation and treatment planning of uveal melanoma. These include digital photography, ultrasonography, angiography and optical coherence tomography. Digital photography is useful for documenting the clinical findings for future comparison and response to treatment. Ultrasonography provides information on tumour biometry, local extension and tumour composition (internal reflectivity). Angiography can be used to assess the degree of tumour vascularity. Newer forms of imaging, including optical coherence tomography (OCT), have excellent resolution and provide detail on surface features.Conclusion:The accuracy of clinical diagnosis of uveal melanoma exceeds 99 % when using currently available imaging modalities. There are advantages and disadvantages to each modality depending on tumour location, size, surface characteristics and internal structure. Ancillary techniques such as computed tomography, magnetic resonance imaging and positron emission tomography may be useful in atypical lesions or in the surveillance for metastatic disease.

Abstract A20: Development and pharmacological assessment of new models of orthotopic primary human uveal melanoma and retinoblastoma xenografts.

Abstract Background: The treatment of both uveal melanoma and retinoblastoma could require enucleation in unfavorable prognostic disease. In order to allow pharmacological assessment of innovative intraocular treatments in more relevant and predictive models, we have developed preclinical orthotopic xenografts of both primary human uveal melanoma (UM) and retinoblastoma (Rb) into immunodeficient mice. Materials and methods: Orthotopic models of human UM and Rb have been developed from two panels of subcutaneous xenografts previously established and characterized in the laboratory (Némati et al 2010; Aerts et al 2010), i.e. 6 UM models (MP34, MP41, MP42, MP55, MP65, and MM26) and 3 Rb models (RB102, RB111, and RB200). Mice bearing xenografts were sacrificed and tumors were dissected to obtain a suspension of fresh tumor cells at a concentration of 8000 cells/l in DMEM serum-free medium. Under intraperitoneal anesthesia, 2 l of cell suspension was injected into the subretinal space of the right eye for 3 groups of mice using a 32G needle via a Hamilton syringe. Each group was constituted by 3 to 6 SCID mice. After sub-retinal injection, ophthalmic examination of the mice was performed weekly. When tumor cells invaded vitreal cavity and anterior chamber, the mice were sacrificed for ophthalmological pathological analyzes. Finally, using the RB200 model, we have then evaluated the efficacy of 2 μl intraocular administration of bevacizumab (25 mg/kg/week for 4 weeks), melphalan (500 μg/kg/week for 4 weeks), and carboplatin (100 μg/kg/week for 4 weeks). Results: The 6 UM cells developed in all injected eyes, 6 to 10 weeks after orthotopic transplantation. Pathological analyzes confirmed UM diagnosis and conservation of histological sub-type, i.e. epithelioid and/or spindle cell, than in corresponding patient's tumors and subcutaneous xenografts. Liver tissues examination is on-going. Rb tumor cells developed in all injected eyes 4 to 6 weeks after orthotopic transplantation for RB102 and RB200. In contrast, no tumor growth was observed in injected eyes of the RB111 model. Pathological examination of the injected eyes confirmed the presence of a massive infiltration of the retina, vitreous and anterior chamber by retinoblastoma cells. Finally, we have observed a high efficacy of intraocular administration of carboplatin (17% of intraocular tumors), but not bevacizumab (100%) nor melphalan (67%), in the RB200 model than in the control group. Conclusions: We have developed relevant and available preclinical models of human UM and Rb that allow pharmacological assessment of intraocular standard therapies. We will now evaluate innovative therapeutic approaches in such a tumor situation. Némati et al. Clin Cancer Res 2010;16:2352–2362. Aerts et al. Photodiagnosis Photodyn Ther 2010;7:275–283. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A20.