Improved Staging of Ciliary Body and Choroidal Melanomas Based on Estimation of Tumor Volume and Competing Risk Analyses.

PURPOSE: The current, 8th edition of the American Joint Committee on Cancer (AJCC) anatomic classification and staging model for uveal melanoma does not fully separate survival estimates for patients with advanced stages of the disease (e.g., IIIB and IIIC). Furthermore, some tumors in higher size categories have a smaller volume than tumors in lower categories. Therefore, we developed a novel model for prognostication of metastatic mortality based on estimations of tumor volume. DESIGN: Retrospective, multicenter case series of patients with uveal melanoma involving the choroid, ciliary body, or both. PARTICIPANTS: Six thousand five hundred twenty-eight consecutively registered patients treated at 3 tertiary ocular oncology centers on 2 continents between 1981 and 2022. METHODS: Data on survival, tumor size, and extent were collected for all 6528 patients. Tumor volume was estimated using a simple equation based on largest basal diameter and thickness. Volume-based size categories and stages were developed and validated in independent patient cohorts using competing risk analyses, and correlations with cytogenetic and cytomorphologic features were examined. MAIN OUTCOME MEASURE: Cumulative incidence of metastatic death. RESULTS: The 6528 patients were distributed over 7 stages based on estimated tumor volume and anatomic extent (V stages IA, IB, IIA, IIB, IIIA, IIIB, and IIIC), with a 15-year incidence of metastatic death ranging from 7% to 77%. A new category, V1min, and corresponding stage IA, were introduced, indicating an excellent prognosis. Metastatic mortality in V stage IIIC was significantly higher than that in V stage IIIB (P = 0.03), whereas incidence curves crossed for patients in AJCC stages IIIC vs. IIIB (P = 0.53). Univariable and multivariable competing risk regressions demonstrated higher Wald statistics for V stages compared with AJCC stages (1152 vs. 1038 and 71 vs. 17, respectively). The frequency of monosomy 3, gain of chromosome 8q, and epithelioid cytomorphologic features increased with tumor volume (R2 = 0.70, R2 = 0.50, and R2 = 0.71, respectively; P < 0.001) and showed similar correlations with both AJCC and V stages. CONCLUSIONS: Anatomic classification and staging of ciliary body and choroidal melanomas based on estimation of tumor volume improves prognostication of metastatic mortality. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Outcome Measures of New Technologies in Uveal Melanoma: Review from the European Vision Institute Special Interest Focus Group Meeting.

Uveal Melanoma (UM) is the most common primary intra-ocular tumor in adults. New diagnostic procedures and basic science discoveries continue to change our patient management paradigms. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on "Outcome Measures of New Technologies in Uveal Melanoma", addressing the latest advances in UM, starting with genetic developments, then moving on to imaging and treatment of the primary tumor, as well as to investigating the most recent developments in treating metastases, and eventually taking care of the patient's wellbeing. This review highlights the meeting's presentations in the context of the published literature.

Impact of COVID-19 pandemic on eye cancer care in United Kingdom.

The COVID-19 pandemic has had an unprecedented impact on the National Health Service in United Kingdom. The UK Ocular Oncology Services evaluated the impact on the adult eye cancer care in the UK. All four adult Ocular Oncology centres participated in a multicentre retrospective review comparing uveal melanoma referral patterns and treatments in a 4-month period during the national lockdown and first wave of the COVID-19 pandemic in 2020 with corresponding periods in previous 2 years. During the national lockdown, referral numbers and confirmed uveal melanoma cases reduced considerably, equalling to ~120 fewer diagnosed uveal melanoma cases compared to previous 2 years. Contrary to the recent trend, increased caseloads of enucleation and stereotactic radiosurgery (p > 0.05), in comparison to fewer proton beam therapy (p < 0.05), were performed. In the 4-month period following lockdown, there was a surge in clinical activities with more advanced diseases (p < 0.05) presenting to the services. As the COVID-19 pandemic continues to mount pressure and reveal its hidden impact on the eye cancer care, it is imperative for the Ocular Oncology Services to plan recovery strategies and innovative ways of working.

Adjuvant External Beam Radiotherapy Following Enucleation of Eyes With Extraocular Extension From Uveal Melanoma.

PURPOSE: To report local disease control and all-cause mortality in patients with extraocular extension (EOE) of uveal melanoma undergoing enucleation followed by observation or external beam radiotherapy (EBRT). METHODS: Charts of patients enucleated between January 1, 1997 and December 31, 2019, with histopathological evidence of EOE of uveal melanoma were reviewed. RESULTS: The cohort comprised 51 patients with a mean age of 67 ± 15 years, 22 (43%) of whom underwent adjuvant postenucleation EBRT. Risk factors for metastasis included presence of epithelioid cells (29/45; 88%), closed loops (20/43; 47%), monosomy 3 (16/25; 64%), and gain of 8q (20/22; 91%). Patients undergoing EBRT had more extensive EOE (median: 5.1 mm vs. 2.6 mm, p = 0.008) and surgical excision was less likely to be histologically complete (2/20; 10% vs. 14/25; 56%, p = 0.002). Local side effects following EBRT were seen in 64% (14/22). At latest follow up, 59% of patients (30/51) were alive, with a median follow up of 1.8 years (interquartile range: 2.9; range: 0.1-6.5]. By Kaplan-Meier survival analysis, the 5- and 10-year overall survival rates were 56% and 12%, respectively. There was no difference in all-cause mortality between those receiving adjuvant EBRT and those who were observed (log rank, p = 0.273). No cases of orbital recurrence were documented. CONCLUSIONS: Orbital EBRT causes significant morbidity. Cases with relatively small EOE undergoing enucleation can be safely observed, without adjuvant EBRT. Multicenter studies are required to better assess the role of EBRT when EOE is more extensive.

Next-Generation Sequencing of Retinoblastoma Identifies Pathogenic Alterations beyond RB1 Inactivation That Correlate with Aggressive Histopathologic Features.

PURPOSE: To determine the usefulness of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation for retinoblastoma. DESIGN: Cohort study. PARTICIPANTS: Thirty-two children with retinoblastoma. METHODS: We performed targeted NGS using the UCSF500 Cancer Panel (University of California, San Francisco, San Francisco, CA) on formalin-fixed, paraffin-embedded tumor tissue along with constitutional DNA isolated from peripheral blood, buccal swab, or uninvolved optic nerve. Peripheral blood samples were also sent to a commercial laboratory for germline RB1 mutation testing. MAIN OUTCOME MEASURES: Presence or absence of germline RB1 mutation or deletion, tumor genetic profile, and association of genetic alterations with clinicopathologic features. RESULTS: Germline mutation or deletion of the RB1 gene was identified in all children with bilateral retinoblastoma (n = 12), and these NGS results were 100% concordant with commercial germline RB1 mutation analysis. In tumor tissue tested with NGS, biallelic inactivation of RB1 was identified in 28 tumors and focal MYCN amplification was identified in 4 tumors (2 with wild-type RB1 and 2 with biallelic RB1 inactivation). Additional likely pathogenic alterations beyond RB1 were identified in 13 tumors (41%), several of which have not been reported previously in retinoblastoma. These included focal amplifications of MDM4 and RAF1, as well as damaging mutations involving BCOR, ARID1A, MGA, FAT1, and ATRX. The presence of additional likely pathogenetic mutations beyond RB1 inactivation was associated with aggressive histopathologic features, including higher histologic grade and anaplasia, and also with both unilateral and sporadic disease. CONCLUSIONS: Comprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features.

Predictors of long-term anxiety and depression in uveal melanoma survivors: A cross-lagged five-year analysis.

OBJECTIVE: Cancer survivors commonly experience long-term anxiety and depression. Anxiety and depression might result from problems emerging during survivorship rather than illness and treatment. This study tested three potential causal paths: (a) concerns about physical symptoms and functional problems and fear of cancer recurrence (FCR) arising during survivorship directly cause anxiety and depression, (b) an indirect path whereby FCR mediates effects of concerns about physical symptoms and functional problems on anxiety and depression, and (c) a reciprocal path whereby anxiety and depression cause concerns about physical symptoms and functional problems and FCR, which exacerbate later anxiety and depression. METHODS: Sample of 453 uveal melanoma survivors who completed observations 6-, 12-, 24-, 36-, 48- and 60-months post-diagnosis and did not miss two consecutive observations. Cross-lagged analyses were conducted to predict Hospital Anxiety and Depression Scale subscale scores. Symptoms and functional problems were measured using the EORTC OPT 30 scale, and FCR operationalised by the EORTC OPT 30 worry about recurrence scale. Covariates were age, gender, treatment modality, and visual acuity of the fellow eye and chromosome-3 status (which accurately predicts 10-year survival), worry and anxiety or depression. RESULTS: All paths received some support, although the indirect path emerged only for anxiety in females. Concerns about physical symptoms, functional problems, and FCR originated in survivorship and appeared to both influence and be influenced by anxiety and depression. CONCLUSIONS: Findings emphasise the importance of actively monitoring survivors to prevent, detect, and intervene in the development of anxiety and depression during survivorship.

MORTALITY OF PATIENTS WITH UVEAL MELANOMA DETECTED BY DIABETIC RETINOPATHY SCREENING.

PURPOSE: To investigate whether early detection and treatment of uveal melanoma by screening was associated with a lower mortality rate. METHODS: Retrospective assessment of prospectively collected data comparing 132 patients with uveal melanoma referred by the National Diabetic Screening Service with 608 control patients referred through other means. RESULTS: Mean tumor diameter was smaller in the diabetic screening group (11.1 mm vs. 12.5 mm) as was tumor thickness (3.4 mm vs. 5.4 mm). The prevalence of high-risk monosomy 3 was also lower (17/40, 43% vs. 62/110, 56%). Despite a higher rate of systemic comorbidities in the patients diagnosed through screening and despite older age at diagnosis, the 5-year all-cause mortality was similar in both groups (17% vs. 20%); however, the metastatic mortality was lower in the diabetic screening group (11/132, 8% vs. 95/608, 16%). CONCLUSION: Despite higher rates of comorbidities, the patients detected at diabetic screening had a lower 5-year mortality rate. The diabetic screening programme enabled detection and treatment of posterior uveal melanomas at an earlier stage. However, the confounding factors of lead and length time bias are not to be ignored.

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

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.

A Case of Metastatic Atypical Neuroendocrine Tumor with ALK Translocation and Diffuse Brain Metastases.

A challenge in precision medicine requires identification of actionable driver mutations. Critical to such effort is the deployment of sensitive and well-validated assays for mutation detection. Although identification of such alterations within the tumor tissue remains the gold standard, many advanced non-small cell lung cancer cases have only limited tissue samples, derived from small biopsies or fine-needle aspirates, available for testing. More recently, noninvasive methods using either circulating tumor cells or tumor DNA (ctDNA) have become an alternative method for identifying molecular biomarkers and screening patients eligible for targeted therapies. In this article, we present a case of a 52-year-old never-smoking male who presented with widely metastatic atypical neuroendocrine tumor to the bones and the brain. Molecular genotyping using DNA harvested from a bone metastasis was unsuccessful due to limited material. Subsequent ctDNA analysis revealed an ALK translocation. The clinical significance of the mutation in this particular cancer type and therapeutic strategies are discussed. KEY POINTS: To our knowledge, this index case represents the first reported ALK translocation identified in an atypical carcinoid tumor.Liquid biopsy such as circulating tumor DNA is a feasible alternative platform for identifying sensitizing genomic alterations.Second-generation ALK inhibitors represent a new paradigm for treating ALK-positive patients with brain metastases.

Can DMCO Detect Visual Field Loss in Neurological Patients? A Secondary Validation Study.

Unrecognized visual field loss is caused by a range of blinding eye conditions as well as serious brain diseases. The commonest cause of asymptomatic visual field loss is glaucoma. No screening tools have been proven cost-effective. Damato Multifixation Campimetry Online (DMCO), an inexpensive online test, has been evaluated as a future cost-beneficial tool to detect glaucoma. To further validate DMCO, this study aimed to test DMCO in a preselected population with neurological visual field loss. METHODS: The study design was an evaluation of a diagnostic test. Patients were included if they had undergone surgery for epilepsy during 2011-2014, resulting in visual field loss. They were examined with DMCO and results were compared with those obtained with the Humphrey Field Analyzer (30:2 SITA-Fast). DMCO sensitivity and specificity were estimated with 95% confidence intervals. RESULTS: The cohort comprised 40 patients (25 female and 15 male) with a mean age of 39 years (range 17-60 years). The mean visual acuity was >1.0 and all eyes had an intraocular pressure <21 mm Hg. Sensitivity and specificity of DMCO compared to the reference standard were 72.7 and 96.3%, respectively. CONCLUSIONS: DMCO detects moderate-to-severe homonymous quadrantanopia; it can be useful in settings where the current practice is confrontation visual field examination, and where standard conventional perimetry is not available.

Porous Versus Nonporous Orbital Implants After Enucleation for Uveal Melanoma: A Randomized Study.

PURPOSE: To compare hydroxyapatite with acrylic implants after enucleation for uveal melanoma with respect to eyelid position, ocular motility, implant complications, and patient satisfaction. METHODS: Patients undergoing primary enucleation for uveal melanoma between May 2005 and November 2012 at the Liverpool Ocular Oncology Centre, United Kingdom, were randomized between hydroxyapatite and acrylic implants. Questionnaires were sent to patients and ocularists to comment on the main outcomes. RESULTS: A total of 416 patients were recruited in the study, of whom 281 were included, with 49.5% (139/281) and 50.5% (142/281) receiving a hydroxyapatite (HA) or acrylic (AC) implant. Mailed questionnaires completed at ≥18 months by patients showed no significant differences between the groups in eyelid position, prosthetic motility, socket complications, and patient satisfaction. Complications included implant extrusion (1% vs 4%), enophthalmos (26% vs 26%), and superior sulcus deformity (24% vs 24%) with HA and AC implants, respectively, (Fisher exact test p > 0.0125 in all, Bonferroni correction). Questionnaires completed by ocularists indicated no significant differences in eyelid opening, prosthetic motility, and other complications at 6 months (Fisher exact test, p > 0.05 in all); there was a higher prevalence of ptosis with AC than HA implants (46% vs 25%, p = 0.03) and a greater need for ocularists' treatment with HA than AC (50% vs 28%, p = 0.03). CONCLUSIONS: Patient-reported outcomes after enucleation for uveal melanoma indicate no major differences between hydroxyapatite and acrylic implants in surgical outcomes and patient satisfaction. There was a higher prevalence of ptosis with AC and a greater need of ocularists' visits with HA at around 6 months observed by ocularists.

The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group.

PURPOSE: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. DESIGN: Retrospective, multicenter observational study. PARTICIPANTS: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. METHODS: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. MAIN OUTCOME MEASURES: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. RESULTS: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. CONCLUSIONS: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.

Management of Primary Acquired Melanosis, Nevus, and Conjunctival Melanoma.

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.

Cluster analysis of multiplex ligation-dependent probe amplification data in choroidal melanoma.

PURPOSE: To determine underlying correlations in multiplex ligation-dependent probe amplification (MLPA) data and their significance regarding survival following treatment of choroidal melanoma (CM). METHODS: MLPA data were available for 31 loci across four chromosomes (1p, 3, 6, and 8) in tumor material obtained from 602 patients with CM treated at the Liverpool Ocular Oncology Center (LOOC) between 1993 and 2012. Data representing chromosomes 3 and 8q were analyzed in depth since their association with CM patient survival is well-known. Unsupervised k-means cluster analysis was performed to detect latent structure in the data set. Principal component analysis (PCA) was also performed to determine the intrinsic dimensionality of the data. Survival analyses of the identified clusters were performed using Kaplan-Meier (KM) and log-rank statistical tests. Correlation with largest basal tumor diameter (LTD) was investigated. RESULTS: Chromosome 3: A two-cluster (bimodal) solution was found in chromosome 3, characterized by centroids at unilaterally normal probe values and unilateral deletion. There was a large, significant difference in the survival characteristics of the two clusters (log-rank, p<0.001; 5-year survival: 80% versus 40%). Both clusters had a broad distribution in LTD, although larger tumors were characteristically in the poorer outcome group (Mann-Whitney, p<0.001). Threshold values of 0.85 for deletion and 1.15 for gain optimized the classification of the clusters. PCA showed that the first principal component (PC1) contained more than 80% of the data set variance and all of the bimodality, with uniform coefficients (0.28±0.03). Chromosome 8q: No clusters were found in chromosome 8q. Using a conventional threshold-based definition of 8q gain, and in conjunction with the chromosome 3 clusters, three prognostic groups were identified: chromosomes 3 and 8q both normal, either chromosome 3 or 8q abnormal, and both chromosomes 3 and 8q abnormal. KM analysis showed 5-year survival figures of approximately 97%, 80%, and 30% for these prognostic groups, respectively (log-rank, p<0.001). All MLPA probes within both chromosomes were significantly correlated with each other (Spearman, p<0.001). CONCLUSIONS: Within chromosome 3, the strong correlation between the MLPA variables and the uniform coefficients from the PCA indicates a lack of evidence for a signature gene that might account for the bimodality we observed. We hypothesize that the two clusters we found correspond to binary underlying states of complete monosomy or disomy 3 and that these states are sampled by the complete ensemble of probes. Consequently, we would expect a similar pattern to emerge in higher-resolution MLPA data sets. LTD may be a significant confounding factor. Considering chromosome 8q, we found that chromosome 3 cluster membership and 8q gain as traditionally defined have an indistinguishable impact on patient outcome.

Phantom Eye Syndrome: Patient Experiences after Enucleation for Uveal Melanoma.

PURPOSE: Patients undergoing enucleation for uveal melanoma need to be informed of the possibility of phantom eye syndrome (PES). The number with uveal melanoma in PES studies has been small. Aims were to: (1) determine the prevalence, symptoms, and characteristics of PES and to test associations of PES symptoms with sociodemographic and clinical characteristics; (2) examine the interrelatedness of PES symptoms; and (3) explore the emotional valence of PES and the relationship to anxiety and depression. DESIGN: Cross-sectional questionnaire. PARTICIPANTS: Patients (n = 179) with uveal melanoma enucleated 4 to 52 months previously. METHODS: Questionnaire on PES. Responses to a routine audit of mood obtained from clinical records. MAIN OUTCOME MEASURES: Patients were asked about 3 symptoms: pain, visual sensations, and a feeling of seeing through the removed eye. Mood was assessed by the Hospital Anxiety and Depression Scale. RESULTS: Of 179 respondents, 108 (60.3%) experienced symptoms: 86 reported (48%) visual sensations, 50 reported (28%) seeing, and 42 reported (23%) pain; 14 (7.8%) reported all 3 symptoms. At the time of the questionnaire, 31 (17%) experienced 1 or more symptoms daily. Women were more likely to report pain (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.08-4.40). Younger patients at enucleation were more likely to report pain (t = 4.13; degrees of freedom (df), 177; P < 0.001) and visual sensations (t = 2.11; df, 177; P < 0.05). Patients studied sooner after enucleation were more likely to report seeing (Mann-Whitney U, 2343; P < 0.05). Pain and seeing were intercorrelated (chi-square, 5.47; Φ = 0.18; df, 1; P < 0.05), pain with visual sensations (chi-square, 3.91; Φ = 0.15; df, 1; P < 0.05) and seeing with visual sensations (chi-square, 34.22; Φ = 0.45; df, 1; P < 0.001). Twenty of 108 patients (18.5%) found symptoms disturbing, and 21 of 108 (19.4%) pleasurable. Patients reporting pain were more anxious (OR, 3.53; 95% CI, 1.38-9.03) and depressed (OR, 13.26; 95% CI, 3.87-46.21). CONCLUSIONS: Patients should be informed of PES symptoms. Pain may indicate anxiety or depression; this needs research to determine cause and effect.

How do patients with uveal melanoma experience and manage uncertainty? A qualitative study.

OBJECTIVES: Cancer survivors experience uncertainty about the future, which can be distressing. A prognostication tool is available for uveal melanoma survivors, which can provide accurate estimates of life expectancy - a key source of uncertainty. Accurate prognostic information has not previously been available for healthy cancer survivors. The aims of this study were to identify how patients experience prognostic information and how it affects their experience of uncertainty. METHODS: Semi-structured interviews were conducted with 25 healthy survivors of uveal melanoma 6-60 months after treatment (approximately 8-62 months after receiving prognostic information). Data were analysed qualitatively. RESULTS: Patients did not feel that the prognostic information relieved uncertainty, which still overshadowed their lives. Different prognoses engendered different experiences of uncertainty. Those receiving poor life expectancy estimates reported uncertainties regarding the timing and form of metastases that they were likely to experience, but they also used uncertainty to justify feeling hopeful. Those receiving good prognoses were often unable wholly to accept these. Patients whose test results failed or were intermediate retained their original uncertainties. Patients managed their uncertainties by suppressing thoughts about them and by trusting in the care of clinicians and the health-care system. CONCLUSIONS: Uncertainty in the context of uveal melanoma is a complex and multifaceted experience that is not easily resolved by prognostication. Additional approaches are needed to help patients with the uncertainty that persists despite prognostication.

Single nucleotide polymorphism array analysis of uveal melanomas reveals that amplification of CNKSR3 is correlated with improved patient survival.

Metastatic death from uveal melanoma occurs almost exclusively with tumors showing monosomy of chromosome 3. However, approximately 5% of patients with a disomy 3 uveal melanoma develop metastases, and a further 5% of monosomy 3 uveal melanoma patients exhibit disease-free survival for >5 years. In the present study, whole-genome microarrays were used to interrogate four clinically well-defined subgroups of uveal melanoma: i) disomy 3 uveal melanoma with long-term survival; ii) metastasizing monosomy 3 uveal melanoma; iii) metastasizing disomy 3 uveal melanoma; and iv) monosomy 3 uveal melanoma with long-term survival. Cox regression and Kaplan-Meier survival analysis identified that amplification of the CNKSR3 gene (log-rank, P = 0.022) with an associated increase in its protein expression (log-rank, P = 0.011) correlated with longer patient survival. Although little is known about CNKSR3, the correlation of protein expression with increased survival suggests a biological function in uveal melanoma, possibly working to limit metastatic progression of monosomy 3 uveal melanoma cells.