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Melanoma: HELP
Articles by Bertil E. Damato
Based on 92 articles published since 2010
(Why 92 articles?)
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Between 2010 and 2020, B. Damato wrote the following 92 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Guideline Uveal Melanoma UK National Guidelines. 2015

Nathan, P / Cohen, V / Coupland, S / Curtis, K / Damato, B / Evans, J / Fenwick, S / Kirkpatrick, L / Li, O / Marshall, E / McGuirk, K / Ottensmeier, C / Pearce, N / Salvi, S / Stedman, B / Szlosarek, P / Turnbull, N / Anonymous4080839. ·Mount Vernon Cancer Centre, Northwood, Middlesex, UK. Electronic address: nathan.pd@gmail.com. · Ocular Oncology Service, St Bartholomew's and Moorfields Eye Hospital, London, UK. · Department Molecular and Clinical Cancer Medicine, University of Liverpool, UK. · OcuMel UK, UK. · Royal Liverpool University Hospital, Liverpool, UK. · University Hospital Aintree, Liverpool, UK. · Patient Representative, UK. · Moorfields Eye Hospital, London, UK. · The Clatterbridge Cancer Centre, NHS Foundation Trust, Liverpool, UK. · Southampton University Hospitals and University of Southampton, UK. · University Hospital Southampton, Southampton, UK. · Royal Hallamshire Hospital, Sheffield, UK. · Southampton University Hospitals, NHS Trust, Southampton, UK. · St Bartholomew's Hospital, UK; Barts Cancer Institute, Queen Mary University of London, London, UK. · Project Manager, London, UK. ·Eur J Cancer · Pubmed #26278648.

ABSTRACT: The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website.

2 Editorial Predicting Choroidal Melanoma Regression after Brachytherapy. 2018

Damato, Bertil. ·San Francisco, California. Electronic address: Bertil.Damato@UCSF.edu. ·Ophthalmology · Pubmed #29681297.

ABSTRACT: -- No abstract --

3 Review Tebentafusp: T Cell Redirection for the Treatment of Metastatic Uveal Melanoma. 2019

Damato, Bertil E / Dukes, Joseph / Goodall, Howard / Carvajal, Richard D. ·Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. Bertil.Damato@NHS.net. · Immunocore Limited, 101 Park Drive, Milton Park, Abingdon, Oxon OX14 4RY, UK. · Department of Medicine, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, HIP 9, New York, NY 10032, USA. ·Cancers (Basel) · Pubmed #31336704.

ABSTRACT: Metastatic disease from uveal melanoma occurs in almost 50% of patients suffering from this ocular tumour, with median survival from development of symptoms being around 1 year. In contrast to cutaneous melanoma, kinase inhibitors and immune checkpoint inhibitors are usually ineffective in patients with metastatic uveal melanoma. Tebentafusp is a novel form of immunotherapy based on the immune-mobilising monoclonal T cell receptor against cancer (ImmTAC) platform, which comprises a soluble T cell receptor that is fused to an anti-CD3 single-chain variable fragment. The T cell receptor domain of tebentafusp targets cells present a human leukocyte antigen-A*02:01 complexed with a peptide derived from the melanoma-associated antigen gp100, which is expressed strongly by melanoma cells, weakly by normal melanocytes and minimally by other tissues. The anti-CD3 domain recruits CD3+ T cells (and, indirectly, other immune cells), redirecting these to the melanoma cells. The most common adverse events with tebentafusp are manageable and usually transient. Early survival data in patients with metastatic uveal melanoma are promising when considered alongside historical data. Based on these encouraging results, a randomised study comparing tebentafusp to investigator's choice of therapy in metastatic uveal melanoma is ongoing.

4 Review Ocular treatment of choroidal melanoma in relation to the prevention of metastatic death - A personal view. 2018

Damato, Bertil. ·Ocular Oncology Service, Department of Ophthalmology, University of California San Francisco, 10 Koret Way, San Francisco, CA 94143, USA. Electronic address: Bertil.Damato@UCSF.edu. ·Prog Retin Eye Res · Pubmed #29571968.

ABSTRACT: About 50% of patients with choroidal melanoma develop metastatic disease, despite successful eradication of the primary tumor. Patient care is complicated by the fact that we do not know whether ocular treatment ever influences survival and if so in whom. Some authorities believe that metastatic spread is never preventable, because it has always occurred by the time the ocular tumor is detected. Others hold the view that metastatic spread can occur late, at least in some patients, in whom timely and successful treatment is life-saving. Some melanomas never seem to metastasize, even if they reach an advanced stage. It is likely that many patients are undergoing futile enucleation or experiencing severe ocular morbidity and visual loss from excessive radiation safety margins in the hope of living longer. Some of these patients would do better with tumor resection, often rejected because of concerns about iatrogenic tumor dissemination. At the same time, many patients with a small melanoma are being left untreated for years until growth is documented, possibly missing opportunities for prolonging life. Metastatic disease is highly likely when genetic tumor analysis detects monosomy 3, chromosome 8q gain, a class 2 gene expression profile, and/or BAP1 loss. Do these lethal genetic aberrations ever develop while the patient is under observation? If so, can these be predicted by genetic analysis? Do lethal mutations and metastasis ever occur because ocular treatment has failed to eradicate the tumor completely? Answers to these questions would profoundly change the management of patients with uveal melanoma.

5 Review Uveal Melanoma Treatment and Prognostication. 2017

Dogrusöz, Mehmet / Jager, Martine J / Damato, Bertil. ·Department of Ophthalmology, LUMC, Leiden, The Netherlands. · Departments of Ophthalmology and Radiation Oncology, University of California, San Francisco, California, United States. ·Asia Pac J Ophthalmol (Phila) · Pubmed #28399342.

ABSTRACT: Approximately 90% of uveal melanoma develop in the choroid, with the remainder arising in the ciliary body or the iris. The treatment of uveal melanoma is aimed at conserving the eye and useful vision, and, if possible, preventing metastatic disease. Enucleation is now reserved for tumors that are large and/or involve the optic disc, having largely been replaced by various forms of radiotherapy (plaque brachy-therapy, proton beam or stereotactic radiotherapy) and laser therapy. Whereas iridectomy and iridocyclectomy are widely performed, transscleral exoresection of choroidal tumors is performed only in a few centers because it requires special skills and hypotensive anesthesia. Transretinal endoresection using vitrectomy equipment is easier but controversial because of concerns about tumor seeding. Long-term postoperative surveillance is necessary to identify and treat local tumor recurrence and any other complications, such as radiation-induced morbidity, and to provide counseling to the patient. Factors predicting metastasis include older age, large tumor size, ciliary body involvement, extraocular spread, epithelioid cytomorphology, chromosome 3 loss and chromosome 8q gain, class 2 gene expression profile, loss of BRCA1-associated protein-1 (BAP1), and the presence of inflammation. Prognostication is enhanced by multi-variable analysis combining clinical, histologic, and genetic factors, also taking the patient's age and sex into account. As there is a lack of options for treating metastases, much research is focused on identifying potential therapeutic targets.

6 Review Management of Primary Acquired Melanosis, Nevus, and Conjunctival Melanoma. 2016

Kao, Andrew / Afshar, Armin / Bloomer, Michele / Damato, Bertil. ·Department of Ophthalmology, University of California, San Francisco, CA 94143, USA. Bertil.Damato@ucsf.edu. ·Cancer Control · Pubmed #27218788.

ABSTRACT: BACKGROUND: The management of conjunctival melanoma is difficult because of the rarity of the disease, confusing terminology, high rates of local tumor recurrence, controversies regarding treatment, a poor evidence base, unreliable prognostication, and significant mortality rates. METHODS: The medical literature was reviewed, focusing on treatment and management options for conjunctival melanoma. Recent trends and developments were summarized with respect to terminology, local treatment, histology, genetic analysis, prognostication, and systemic treatment, highlighting the scope for research and possible improvements in patient care. RESULTS: Histopathological diagnostic terminology for primary acquired melanosis is being superseded by more explicit terminology, thus differentiating hypermelanosis from conjunctival melanocytic intraepithelial neoplasia. Topical chemotherapy and increased use of adjunctive radiotherapy have helped improve rates of local tumor control. Use of exenteration has become rare. Regional and systemic metastases are common in patients with nonbulbar conjunctival melanoma, although long-term survivors with metastases are growing in number. Prognostication is mainly based on tumor size and location, but histological and genetic data into multivariate analyses will soon be incorporated. The role of sentinel lymph-node biopsy continues to be controversial. Chemotherapy for metastatic disease is being superseded by targeted therapy based on genetic abnormalities such as BRAF mutations. CONCLUSIONS: The management of conjunctival melanoma requires expert care from an experienced, multidisciplinary team. The goal of therapy is to provide good local tumor control with minimal morbidity, high-quality pathology, and adequate psychological support. Maximizing patient enrollment in multicenter clinical trials is likely to strengthen evidence-based decision-making.

7 Review Uveal melanoma: evidence for efficacy of therapy. 2015

Afshar, Armin R / Damato, Bertil E. · ·Int Ophthalmol Clin · Pubmed #25436491.

ABSTRACT: -- No abstract --

8 Review Intraocular collision tumour: case report and literature review. 2013

Coupland, Sarah E / Dodson, Andrew / Liu, Hongxiang / Du, Ming-Qing / Angi, Martina / Damato, Bertil E. ·Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 5th Floor Duncan Building, Daulby Street, Liverpool, L69 3GA, UK. s.e.coupland@liverpool.ac.uk ·Graefes Arch Clin Exp Ophthalmol · Pubmed #23232651.

ABSTRACT: BACKGROUND: "Collision" tumours consist of different neoplasms coexisting within a single lesion. Whilst quite common in the skin, the gastrointestional tract, and the ovaries, intraocular collision tumours are exceedingly rare. We describe an exceptional case of a combined uveal melanoma and intraocular plasmacytoma. METHODS: Observational case report. A 61-year-old woman underwent enucleation for rubeotic glaucoma and cells in the anterior chamber after proton-beam radiotherapy of a cilio-choroidal melanoma of the right eye. Examination of the enucleated eye was performed with immunohistochemistry, multiplex ligation dependent probe amplification (MLPA), and polymerase chain reaction (PCR) for immunoglobulin heavy- and light-chain gene rearrangements. A review of the literature on ocular collision tumours and uveal involvement by plasma cell neoplasms was also performed. RESULTS: Morphological, immunophenotypical, and genotypical examination of the tumour revealed the co-existence of both a melanoma and a plasmacytoma within the choroid and ciliary body. The glaucoma was caused by extensive infiltration of the iris and trabecular meshwork by the plasmacytoma cells. Review of the literature revealed only four collision tumours involving the eyelid and three involving the choroid. All three intraocular collision tumours consisted of uveal melanoma and choroidal non-Hodgkin lymphoma. Uveal involvement by plasma cell neoplasms is also extremely rare, with only six reported cases. CONCLUSIONS: This is the first documented intraocular collision tumour consisting of a uveal melanoma and isolated plasmacytoma. If a patient presents with 'uveitis' after proton-beam radiotherapy of a cilio-choroidal melanoma, there may be scope for performing biopsies to determine whether the lymphoid infiltrate is reactive or neoplastic.

9 Review Conjunctival melanoma and melanocytic intra-epithelial neoplasia. 2013

Kenawy, N / Lake, S L / Coupland, S E / Damato, B E. ·St Paul's Eye Unit, Liverpool Ocular Oncology Service, Royal Liverpool University Hospital, Liverpool, UK. nkenawy@liv.ac.uk ·Eye (Lond) · Pubmed #23222568.

ABSTRACT: The rarity of conjunctival melanoma has impeded progress in the management of patients with this cancer; however, much progress has occurred in recent years. Primary acquired melanosis is now differentiated histologically into hypermelanosis and conjunctival melanocytic intra-epithelial neoplasia, for which an objective reproducible scoring system has been developed. Mapping and clinical staging of conjunctival disease has improved. Adjunctive radiotherapy and topical chemotherapy have made tumour control more successful, with reduced morbidity. Genetic analyses have identified BRAF and other mutations, which may predict responsiveness to new chemotherapeutic agents, for example Vemurafenib, should metastatic disease develop. Multicentre studies are under way to enhance survival prediction by integrating clinical stage of disease with histological grade of malignancy and genetic abnormalities. Such improved prognostication would not only be more relevant to individual patients, but would also provide greater opportunities for basic science research.

10 Review Molecular pathology of uveal melanoma. 2013

Coupland, S E / Lake, S L / Zeschnigk, M / Damato, B E. ·Pathology, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. s.e.coupland@liverpool.ac.uk ·Eye (Lond) · Pubmed #23222563.

ABSTRACT: Like other cancers, uveal melanomas (UM) are characterised by an uncontrolled, clonal, cellular proliferation, occurring as a result of numerous genetic, and epigenetic aberrations. Signalling pathways known to be disrupted in UM include: (1) the retinoblastoma pathway, probably as a result of cyclin D1 overexpression; p53 signalling, possibly as a consequence of MDM2 overexpression; and the P13K/AKT and mitogen-activated protein kinase/extracellular signal-related kinase pathway pathways that are disturbed as a result of PTEN and GNAQ/11 mutations, respectively. Characteristic chromosomal abnormalities are common and include 6p gain, associated with a good prognosis, as well as 1p loss, 3 loss, and 8q gain, which correlate with high mortality. These are identified by techniques such as fluorescence in situ hybridisation, comparative genomic hybridisation, microsatellite analysis, multiplex ligation-dependent probe amplification, and single-nucleotide polymorphisms. UM can also be categorised by their gene expression profiles as class 1 or class 2, the latter correlating with poor survival, as do BRCA1-associated protein-1 (BAP1) inactivating mutations. Genetic testing of UM has enhanced prognostication, especially when results are integrated with histological and clinical data. The identification of abnormal signalling pathways, genes and proteins in UM opens the way for target-based therapies, improving prospects for conserving vision and prolonging life.

11 Review Effects of radiotherapy on uveal melanomas and adjacent tissues. 2013

Groenewald, C / Konstantinidis, L / Damato, B. ·Ocular Oncology Service, St Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, UK. ·Eye (Lond) · Pubmed #23196647.

ABSTRACT: Most uveal melanomas are treated with radiotherapy. An adequate understanding of the effects of radiation on the tumour and the healthy ocular tissues is necessary. Ionizing radiation damages cell membranes, organelles, and DNA. Irradiated cells are lysed or undergo apoptosis, necrosis, and senescence. These effects occur in tumour cells and vascular endothelial cells, resulting in tumour shrinkage, ischaemia, infarction, exudation, and fibrosis, which can cause exudative maculopathy, serous retinal detachment, rubeosis, and neovascular glaucoma (ie, 'toxic tumour syndrome'). Such abnormalities must be distinguished from collateral damage to healthy ocular tissues that receive high doses of radiation, and these include radiation-induced retinopathy, optic neuropathy, choroidopathy, cataract, and scleral necrosis. Radiation retinopathy can be treated effectively with photodynamic therapy, anti-angiogenic agents, and intravitreal steroid injections. In some patients, optic neuropathy may improve with intravitreal steroids or anti-angiogenic agents. Neovascular glaucoma resolves with intra-cameral bevacizumab. Exudative retinal detachment can regress with intra-vitreal steroid injections. Cataract is treated in the usual manner. Scleral necrosis, if severe, may require grafting, possibly using a lamellar flap from the same eye. Depending on the bulk of the residual toxic tumour, treatment can consist of intra-vitreal steroids and/or anti-angiogenic agents, transpupillary thermotherapy or photodynamic therapy to the tumour, or surgical removal of the tumour by endo- or exo-resection. Measures aimed at preventing collateral damage include eccentric placement of ruthenium plaques or iodine seeds and delivery of a notched proton beam. The decision to treat a uveal melanoma with radiotherapy requires the ability to manage iatrogenic side effects and complications.

12 Review Personalized treatment of uveal melanoma. 2013

Damato, B / Heimann, H. ·Department of Molecular and Clinical Cancer Medicine, Ocular Oncology Service, Royal Liverpool University Hospital, Liverpool, UK. Bertil@Damato.co.uk ·Eye (Lond) · Pubmed #23174751.

ABSTRACT: Personalized treatment of uveal melanoma involves the tailoring of all aspects of care to the condition, needs, wishes, and fears of the patient, taking account of the individual's circumstances. When selecting between radiotherapy, surgical resection, and phototherapy, or when deciding how best to combine these different therapeutic modalities, it is necessary to understand the patients utilities, with respect to tumour control, visual conservation, and preservation of the eye, so as to prioritize outcomes accordingly. For example, such considerations would influence the width of the safety margins when administering radiotherapy, according to whether the patient considers it more important to conserve vision or to guarantee tumour control. With 'suspicious naevi', the choice between observation, immediate treatment, and biopsy is complicated by the lack of adequate survival data on which to base rational decisions, making it necessary for both patient and doctor to accept uncertainty. Personalized care should involve close relatives, as appropriate. It must also adapt to changes in the patient's needs over time. Such personalized care demands the ability to respond to such needs and the sensitivity to identify these requirements in the first place. Personalized treatment enhances not only the patient's satisfaction but also the 'job satisfaction' of all members of the multidisciplinary team, improving quality of care.

13 Review Local resection of uveal melanoma. 2012

Damato, Bertil E. ·Royal Liverpool University Hospital, Liverpool, UK. ·Dev Ophthalmol · Pubmed #22042014.

ABSTRACT: Local resection of uveal melanoma is aimed at conserving the eye and useful vision while removing any threat of metastatic spread. The tumour can be removed en bloc through a scleral opening (i.e., 'exoresection') or in a piecemeal fashion with a vitreous cutter passed through the retina (i.e., 'endoresection'). Variations of exoresection include iridectomy, iridocyclectomy, cyclochoroidectomy, and choroidectomy. Endoresection can be performed through a retinotomy or under a large retinal flap. Both exoresection and endoresection can be undertaken as a primary procedure, or after other conservative therapy as treatment for recurrent or toxic tumour. Each can be performed in combination with some form of radiotherapy, which can precede or follow the surgical resection. Endoresection should be relatively straightforward for experienced vitreoretinal surgeons; however, exoresection is more challenging, particularly with large and posterior tumours, because of the need for hypotensive anaesthesia and other measures to control intra-operative haemorrhage. In addition to their technical complexities, exoresection and endoresection are limited by intuitive concerns regarding iatrogenic tumour dissemination. When these obstacles are overcome, local resection preserves eyes that would otherwise be inoperable and produces relatively large tumour samples, which are useful for prognostication and research and which may one day have therapeutic value.

14 Review Treatment selection for uveal melanoma. 2012

Damato, Bertil E. ·Ocular Oncology Service, Royal Liverpool University Hospital, Liverpool, UK. ·Dev Ophthalmol · Pubmed #22042010.

ABSTRACT: Uveal melanomas can be treated by various forms and combinations of radiotherapy, phototherapy and local resection, which need to be tailored to the tumour size, location and extent as well as the patient's needs, fears and wishes. Many factors complicate the process of treatment selection and these include limited resources, incomplete knowledge of the patient's condition (e.g. genetic tumour type) and inadequate scientific evidence on which to base decision making. In this chapter, I describe how I select treatment for small, large, juxtapapillary, ciliary and iridal melanomas, respectively, and for melanocytic tumours of indeterminate malignancy. I also describe how I interact with patients so as to select the most suitable treatment in a personalised manner. Finally, I discuss challenges and shortcomings in this aspect of patient care, also providing suggestions for further research in this field.

15 Review Estimating prognosis for survival after treatment of choroidal melanoma. 2011

Damato, Bertil / Eleuteri, Antonio / Taktak, Azzam F G / Coupland, Sarah E. ·Ocular Oncology Service, Royal Liverpool University Hospital, Prescot St, Liverpool L7 8XP, UK. Bertil@damato.co.uk ·Prog Retin Eye Res · Pubmed #21658465.

ABSTRACT: Choroidal melanoma is fatal in about 50% of patients. This is because of metastatic disease, which usually involves the liver. Kaplan-Meier survival curves based only on tumor size and extent do not give a true indication of prognosis. This is because the survival prognosis of choroidal melanoma correlates not only with clinical stage but also with histologic grade, genetic type, and competing causes of death. We have developed an online tool that predicts survival using all these data also taking normal life-expectancy into account. The estimated prognosis is accurate enough to be relevant to individual patients. Such personalized prognostication improves the well-being of patients having an excellent survival probability, not least because it spares them from unnecessary screening tests. Such screening can be targeted at high-risk patients, so that metastases are detected sooner, thereby enhancing any opportunities for treatment. Concerns about psychological harm have proved exaggerated. At least in Britain, patients want to know their prognosis, even if this is poor. The ability to select patients with a high risk of metastasis improves prospects for randomised studies evaluating systemic adjuvant therapy aimed at preventing or delaying metastatic disease. Furthermore, categorization of tissue samples according to survival prognosis enables laboratory studies to be undertaken without waiting many years for survival to be measured. As a result of advances in histologic and genetic studies, biopsy techniques and statistics, prognostication has become established as a routine procedure in our clinical practice, thereby enhancing the care of patients with uveal melanoma.

16 Review Does ocular treatment of uveal melanoma influence survival? 2010

Damato, B. ·Ocular Oncology Service, Royal Liverpool University Hospital, Prescot St, Liverpool L7 8XP, UK. Bertil@Damato.co.uk ·Br J Cancer · Pubmed #20661247.

ABSTRACT: Treatment of uveal (intraocular) melanoma is aimed at prolonging life, if possible conserving the eye and useful vision. About 50% of patients develop fatal metastatic disease despite successful eradication of the primary intraocular tumour. The effect of ocular treatment on survival is unknown, because the same survival data from case series can be interpreted in different ways. Treatment is therefore based on intuition and varies greatly between centres. Randomised trials of treatment vs non-treatment of asymptomatic tumours are desirable but would be controversial, difficult, expensive and possibly inconclusive. Strategies for coping with uncertainty are needed to avoid unethical care.

17 Clinical Trial Concordant chromosome 3 results in paired choroidal melanoma biopsies and subsequent tumour resection specimens. 2015

Coupland, Sarah E / Kalirai, Helen / Ho, Vivian / Thornton, Sophie / Damato, Bertil E / Heimann, Heinrich. ·Department of Pathology, Royal Liverpool and Broadgreen University Hospital Trust (RLBUHT), University of Liverpool, Liverpool, UK. · Department of Ophthalmology, Royal Liverpool and Broadgreen University Hospital Trust (RLBUHT), Liverpool, UK. · Department of Ophthalmology, Royal Liverpool and Broadgreen University Hospital Trust (RLBUHT), Liverpool, UK Ocular Oncology Service, University of California, San Francisco, California, USA. ·Br J Ophthalmol · Pubmed #26206786.

ABSTRACT: BACKGROUND/AIM: The study's aim was to compare chromosome 3 aberrations of choroidal melanoma (CM) as determined by multiplex ligation dependent probe amplification (MLPA) or microsatellite analysis (MSA) in intraocular tumour biopsies with those results obtained from subsequent endoresection/enucleation of the same CM. METHODS: A retrospective cohort of 28 patients with CM seen between 2007 and 2014 at the Liverpool Ocular Oncology Centre was analysed. Prognostic genetic testing, for chromosome 3 status, was performed on all tumour specimens, either by MLPA or MSA, depending on DNA yield. In nine cases genetic testing was performed on a sample taken after radiotherapy; four of these had genetic information pre- and post-radiotherapy. RESULTS: Fourteen biopsy specimens were analysed by MLPA and 14 by MSA. Twenty-seven endoresection or enucleation specimens were analysed by MLPA, and a single enucleation specimen by MSA. Chromosome 3 data showed prognostic concordance for the patient-matched samples in all 28 cases including 4 cases where samples were taken pre pre- and post radiotherapy. Thirteen cases were classified as monosomy 3 and 12 as disomy 3. Two cases had a loss of chromosome arm 3q in both samples and a single case showed loss of 3p in the biopsy sample with complete monosomy 3 in the subsequent enucleation sample taken 5 months later. CONCLUSIONS: Intraocular biopsy of CM yields similar prognostic information to larger surgical specimens. Initial evidence, that genetic testing can be successfully conducted post radiotherapy, is also provided. TRIAL REGISTRATION NUMBER: NITRO trial, ISRCTN35236442.

18 Article Multicenter External Validation of the Liverpool Uveal Melanoma Prognosticator Online: An OOG Collaborative Study. 2020

Cunha Rola, Alda / Taktak, Azzam / Eleuteri, Antonio / Kalirai, Helen / Heimann, Heinrich / Hussain, Rumana / Bonnett, Laura J / Hill, Christopher J / Traynor, Matthew / Jager, Martine J / Marinkovic, Marina / Luyten, Gregorius P M / Dogrusöz, Mehmet / Kilic, Emine / de Klein, Annelies / Smit, Kyra / van Poppelen, Natasha M / Damato, Bertil E / Afshar, Armin / Guthoff, Rudolf F / Scheef, Björn O / Kakkassery, Vinodh / Saakyan, Svetlana / Tsygankov, Alexander / Mosci, Carlo / Ligorio, Paolo / Viaggi, Silvia / Le Guin, Claudia H D / Bornfeld, Norbert / Bechrakis, Nikolaos E / Coupland, Sarah E. ·Liverpool Ocular Oncology Research Group, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, L7 8TX, UK. · Department of Medical Physics and Clinical Engineering, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, L69 3GA, UK. · Department of Biostatistics, University of Liverpool, Liverpool, L69 3GL, UK. · Liverpool Bio-Innovation Hub Biobank, University of Liverpool, Liverpool, L7 8TX, UK. · Department of Ophthalmology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands. · Rotterdam Ocular Melanoma Study Group, Erasmus University Medical Center, Rotterdam, 3008 AE, The Netherlands. · Ocular Oncology, Vitreoretinal Diseases & Surgery, University of California, San Francisco, CA 94143, USA. · Oxford Eye Hospital, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK. · Department of Ophthalmology, University of Rostock, D-18057 Rostock, Germany. · Department of Ophthalmology, University of Lübeck, D- 23538 Lübeck, Germany. · Ocular Oncology Department, Helmholtz Moscow Research Institute of Eye Diseases, 105062 Moscow, Russia. · S.C. Oculistica Oncologica - Ocular Oncology Service, Ente ospedaliero Ospedali Galliera, 16128 Genova, Italy. · DISTAV-Department of Earth, Environment and Life Sciences, University of Genoa, 16132 Genova, Italy. · Laboratory of Human Genetics, IRCCS Istituto G. Gaslini, 16147 Genova, Italy. · Department of Ophthalmology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. · Liverpool Clinical Laboratories, Royal Liverpool University Hospital, Liverpool, L69 3GA, UK. ·Cancers (Basel) · Pubmed #32085617.

ABSTRACT: Uveal melanoma (UM) is fatal in ~50% of patients as a result of disseminated disease. This study aims to externally validate the Liverpool Uveal Melanoma Prognosticator Online V3 (LUMPO3) to determine its reliability in predicting survival after treatment for choroidal melanoma when utilizing external data from other ocular oncology centers. Anonymized data of 1836 UM patients from seven international ocular oncology centers were analyzed with LUMPO3 to predict the 10-year survival for each patient in each external dataset. The analysts were masked to the patient outcomes. Model predictions were sent to an independent statistician to evaluate LUMPO3's performance using discrimination and calibration methods. LUMPO3's ability to discriminate between UM patients who died of metastatic UM and those who were still alive was fair-to-good, with C-statistics ranging from 0.64 to 0.85 at year 1. The pooled estimate for all external centers was 0.72 (95% confidence interval: 0.68 to 0.75). Agreement between observed and predicted survival probabilities was generally good given differences in case mix and survival rates between different centers. Despite the differences between the international cohorts of patients with primary UM, LUMPO3 is a valuable tool for predicting all-cause mortality in this disease when using data from external centers.

19 Article Patient-Reported Outcomes and Quality of Life after Treatment for Choroidal Melanoma. 2019

Damato, Bertil / Hope-Stone, Laura / Cooper, Bruce / Brown, Steve / Heimann, Heinrich / Dunn, Laura. ·University of California, San Francisco, San Francisco, California, USA. · University of Liverpool, Liverpool, United Kingdom. · Stanford University, Stanford, California, USA. ·Ocul Oncol Pathol · Pubmed #31768363.

ABSTRACT: Background/Aims: Patients with choroidal melanoma can develop psychological morbidity because of visual disability, pain, facial deformity, and fears of metastatic disease. The aim of this study was to report on the prevalence of symptoms, moods, and well-being after radiotherapy or enucleation for choroidal melanoma and how these outcomes changed over time. Methods: Participants were mailed questionnaires approximately 6 months following treatment, then annually on every anniversary of their treatment. Results: Soon after enucleation, patients experienced visual difficulties because of loss of stereopsis and visual field and were concerned about their appearance and about metastatic disease. After radiotherapy, patients were more concerned about local tumor recurrence and more troubled by diplopia and headache. Over time, visual difficulties diminished after enucleation but increased in patients who had received radiotherapy, with concerns about metastasis, loss of health, and tumor recurrence diminishing in both groups. Anxiety tended to diminish whereas depression increased, especially after enucleation. Emotional well-being improved after both kinds of treatment, whereas functional and physical well-being diminished after enucleation but improved after radiotherapy. Self-reported quality of life diminished equally with both kinds of treatment. Conclusion: The findings of this study should help physicians understand what patients tend to feel after treatment for choroidal melanoma.

20 Article Next-Generation Sequencing of Uveal Melanoma for Detection of Genetic Alterations Predicting Metastasis. 2019

Afshar, Armin R / Damato, Bertil E / Stewart, Jay M / Zablotska, Lydia B / Roy, Ritu / Olshen, Adam B / Joseph, Nancy M / Bastian, Boris C. ·Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA. · Hellen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. · Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA. · Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. · Computational Biology and Informatics, University of California, San Francisco, San Francisco, CA, USA. · Department of Pathology, University of California, San Francisco, San Francisco, CA, USA. · Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA. ·Transl Vis Sci Technol · Pubmed #31024753.

ABSTRACT: Purpose: To clinically use the UCSF500, a pancancer, next-generation sequencing assay in uveal melanoma (UM) and to correlate results with gene expression profiling (GEP) and predictive factors for metastasis. Methods: Cohort study. Tumor samples of adult UM patients were analyzed with the UCSF500 and GEP. Main outcomes were copy number changes in chromosomes 1, 3, 6, and 8 and mutations in Results: The 62 patients had a mean age of 59 years (range, 24-89 years). Chromosome 3 loss was detected in 30 patients and was associated with larger basal tumor diameter (Wilcoxon rank sum test, Conclusions: UCSF500 detects chromosomal copy number changes and missense mutations that correlate strongly with metastasis predictors, including GEP. Translational Relevance: Next-generation sequencing of UM should enhance survival prognostication.

21 Article Metastatic Cutaneous Melanoma Presenting with Choroidal Metastasis Simulating Primary Uveal Melanoma. 2019

Everett, Lesley / Damato, Bertil E / Bloomer, Michele M / Palmer, James D / Kao, Andrew A / Stewart, Jay M / Afshar, Armin R. ·Department of Ophthalmology, University of California, San Francisco, California, USA. · Northern California Retina-Vitreous Associates, Mountain View, California, USA. ·Ocul Oncol Pathol · Pubmed #30976593.

ABSTRACT: Purpose: To report a case of metastatic cutaneous melanoma presenting with choroidal metastasis simulating primary uveal melanoma. Design: Case report. Method: Presentation of clinical, radiographic, histopathologic, and tumor genetic findings in a patient with cutaneous melanoma with choroidal metastasis. Results: A 50-year-old man with a remote history of stage 1A cutaneous melanoma presented with eye pain, peripheral vision loss, floaters, red eye, and choroidal mass that was originally diagnosed as a primary uveal melanoma at an outside institution; however, subsequent imaging and clinical evaluation demonstrated that this choroidal mass was the first manifestation of widely metastatic cutaneous melanoma (liver, pancreas, lung, bone, brain, and orbit lesions). Histopathologic analysis of the tumor after enucleation was consistent with cutaneous melanoma, and tumor genetic testing was positive for Conclusions: Metastatic cutaneous melanoma to the orbit or globe occurs rarely. Tumor genetic testing may help differentiate metastatic cutaneous melanoma from primary uveal melanoma in cases where the diagnosis is uncertain, and can also inform therapy and prognostic counseling.

22 Article Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome. 2019

Kenawy, Nihal / Kalirai, Helen / Sacco, Joseph J / Lake, Sarah L / Heegaard, Steffen / Larsen, Ann-Cathrine / Finger, Paul T / Milman, Tatyana / Chin, Kimberly / Mosci, Carlo / Lanza, Francesco / Moulin, Alexandre / Schmitt, Caroline A / Caujolle, Jean Pierre / Maschi, Célia / Marinkovic, Marina / Taktak, Azzam F / Heimann, Heinrich / Damato, Bertil E / Coupland, Sarah E. ·Liverpool Ocular Oncology Research Group, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · Aintree University Hospital, Liverpool, UK. · Clatterbridge Cancer Centre, Wirral, UK. · Eye Pathology Section, Department of Pathology and Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. · The New York Eye Cancer Centre, New York. · Ocular Oncology Service, Galliera Hospital, Genoa, Italy. · Ophthalmic Pathology Laboratory and Department of Ophthalmology, Jules Gonin Eye Hospital, Lausanne, Switzerland. · Ophthalmology Department, Oslo University Hospital, Oslo, Norway. · Ophthalmology Department, University Hospital of Nice, Nice, France. · Ophthalmology Department, Leiden University Medical Centre, Leiden, The Netherlands. · Department of Medical Physics and Clinical Engineering, Royal Liverpool University Hospital, Liverpool, UK. · Liverpool Ocular Oncology Centre, Royal Liverpool University Hospital, Liverpool, UK. · Oxford Eye Hospital and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. · Cellular Pathology, Liverpool Clinical Laboratories, Royal Liverpool University Hospital, Liverpool, UK. ·Pigment Cell Melanoma Res · Pubmed #30672666.

ABSTRACT: Relatively little is known about the genetic aberrations of conjunctival melanomas (CoM) and their correlation with clinical and histomorphological features as well as prognosis. The aim of this large collaborative multicenter study was to determine potential key biomarkers for metastatic risk and any druggable targets for high metastatic risk CoM. Using Affymetrix single nucleotide polymorphism genotyping arrays on 59 CoM, we detected frequent amplifications on chromosome (chr) 6p and deletions on 7q, and characterized mutation-specific copy number alterations. Deletions on chr 10q11.21-26.2, a region harboring the tumor suppressor genes, PDCD4, SUFU, NEURL1, PTEN, RASSF4, DMBT1, and C10orf90 and C10orf99, significantly correlated with metastasis (Fisher's exact, p ≤ 0.04), lymphatic invasion (Fisher's exact, p ≤ 0.02), increasing tumor thickness (Mann-Whitney, p ≤ 0.02), and BRAF mutation (Fisher's exact, p ≤ 0.05). This enhanced insight into CoM biology is a step toward identifying patients at risk of metastasis and potential therapeutic targets for systemic disease.

23 Article The Patient's Experience of Ocular Melanoma in the US: A Survey of the Ocular Melanoma Foundation. 2018

Afshar, Armin R / Deiner, Michael / Allen, Grant / Damato, Bertil E. ·Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA. · Ocular Melanoma Foundation, Washington, DC, USA. · Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA. ·Ocul Oncol Pathol · Pubmed #30320098.

ABSTRACT: Background: Ocular melanomas threaten patients with early death, visual handicap, and loss of the eye. The aims of this study were to identify aspects of care that patients with ocular melanoma considered most important and to determine whether patients felt their needs had been adequately addressed. Methods: A cross-sectional study including US ocular melanoma patients and their caregivers. An online survey of US ocular melanoma patients was designed and conducted by the Ocular Melanoma Foundation. Results: The cohort included 180 patients with uveal melanoma and 4 with conjunctival melanoma. Median follow-up was 3 years. A third of patients reported that their uveal melanoma had initially been diagnosed as a nevus. Most uveal melanomas were treated with brachytherapy. Almost 50% of patients had no genetic tumor analysis. Screening methods reported most commonly were computed tomography and liver function tests. Metastatic disease developed in 11% of patients. Few patients (13.3%) reported an offer of psychological support. Most dissatisfaction was with lack of advice on financial aspects of care and lack of psychological counseling, with women tending to express more dissatisfaction with care. Many patients complained about the way ophthalmologists delivered bad news to them. Conclusions: This patients' perspective highlights directions for research, education, and other measures to improve the care of patients with ocular melanoma in the US and elsewhere.

24 Article Prognostication of metastatic death in uveal melanoma patients: A Markov multi-state model. 2018

Eleuteri, Antonio / Taktak, Azzam F G / Coupland, Sarah E / Heimann, Heinrich / Kalirai, Helen / Damato, Bertil. ·Department of Medical Physics and Clinical Engineering, Royal Liverpool and Broadgreen University Hospitals NHS Trust, 1st Floor Duncan Building, L7 8XP, Liverpool, UK; Department of Physics, The Oliver Lodge, University of Liverpool, Oxford St, L69 7ZE, Liverpool, UK. Electronic address: antonio.eleuteri@liverpool.ac.uk. · Department of Medical Physics and Clinical Engineering, Royal Liverpool and Broadgreen University Hospitals NHS Trust, 1st Floor Duncan Building, L7 8XP, Liverpool, UK; Department of Physics, The Oliver Lodge, University of Liverpool, Oxford St, L69 7ZE, Liverpool, UK. Electronic address: afgt@liverpool.ac.uk. · Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Crown Street, L69 3BX, Liverpool, UK. Electronic address: S.E.Coupland@liverpool.ac.uk. · Liverpool Ocular Oncology Centre, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Prescot St, L7 8XP, Liverpool, UK. Electronic address: Heinrich.Heimann@rlbuht.nhs.uk. · Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Crown Street, L69 3BX, Liverpool, UK. Electronic address: H.Kalirai@liverpool.ac.uk. · Liverpool Ocular Oncology Centre, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Prescot St, L7 8XP, Liverpool, UK; Ocular Oncology Service, University of California, 8 Koret Way, San Francisco, USA. Electronic address: Bertil.Damato@ucsf.edu. ·Comput Biol Med · Pubmed #30278339.

ABSTRACT: BACKGROUND/AIMS: Uveal melanoma is fatal in almost 50% of patients. We previously developed a prognostic model to predict all-cause mortality. The aim of this study was to improve our model by predicting metastatic death as a cause-specific event distinct from other causes of death. METHODS: Patients treated in Liverpool were included if they resided in England, Scotland or Wales and if their uveal melanoma involved the choroid. They were flagged at the National Health Service Cancer Registry, which automatically informed us of the date and cause of death of any deceased patients. A semiparametric Markov multi-state model was fitted. Two different baseline hazard rates were assumed, with state transition-specific covariates. For both failure types, age at treatment and sex were used. For the metastatic death case, these factors were added: anterior margin position, largest basal tumour diameter, tumour thickness, extra-ocular extension, presence of epithelioid melanoma cells, presence of closed connective tissue loops, increased mitotic count, chromosome 3 loss, and chromosome 8q gain. Missing data required a multiple-imputation procedure. RESULTS: The cohort comprised 4161 patients, 893 of whom died of metastastic disease with another 772 dying of other causes. The optimism-corrected, bootstrapped C-index for metastatic death prediction was 0.86, denoting very good discriminative performance. Bootstrapped calibration curves at two and five years also showed very good performance. CONCLUSIONS: Our improved model provides reliable, personalised metastatic death prognostication using clinical, histological and genetic information, and it can be used as a decision support tool to individualize patient care in a clinical environment.

25 Article Predictors of anxiety and depression 2 years following treatment in uveal melanoma survivors. 2018

Brown, Stephen L / Hope-Stone, Laura / Heimann, Heinrich / Damato, Bertil / Salmon, Peter. ·Institute of Psychology, Health and Society, University of Liverpool, Liverpool, UK. · Liverpool Ocular Oncology Centre, Royal Liverpool and Broadgreen University Hospital, NHS Trust, Liverpool, UK. · Ocular Oncology Service, University of California, San Francisco, CA, USA. ·Psychooncology · Pubmed #29601654.

ABSTRACT: OBJECTIVE: We examined the role of posttreatment symptoms and functional problems and of worry about recurrent disease (WREC) in predicting probable anxiety and depression cases 24 months after diagnosis in survivors of posterior uveal melanoma. We examined whether WREC mediates links between symptoms, functional problems, and probable anxiety and depression cases. METHODS: Prospective cohort study of 261 treated uveal melanoma survivors 6, 12, and 24 months after diagnosis. Hierarchical logistic regression analyses predicting anxiety and depression 24 months after diagnosis identified by Hospital Anxiety and Depression Scale cutoff scores. Symptoms, functional problems, and WREC 6-month posttreatment were entered into the analyses as predictors, then the same variables at 12 months. We controlled anxiety or depression at 6 and 12 months and chromosome 3 status, which accurately predicts 10-year survival. Mediation of links between 6-month symptoms and functional problems and 24-month anxiety and depression by 12-month WREC was tested. RESULTS: Anxiety caseness at 24 months was predicted by 6-month ocular irritation, headache, and functional problems and 12-month WREC. Depression caseness at 24 months was predicted by 6-month headache and functional problems. Worry about recurrent disease at 12 months mediated prediction of anxiety caseness by 6-month symptoms and functional problems. Chromosome 3 status predicted neither anxiety nor depression. CONCLUSIONS: Survivors reporting symptoms, functional problems, and WREC should be monitored for anxiety and depression. Appropriate reassurance that symptoms do not signify future disease might help prevent anxiety.

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