Purpose: To report the clinical features and epidemiology of uveal melanoma in Ireland. Methods: This was an observational study of 253 patients with a new diagnosis of uveal melanoma between June 2010 and December 2015. Main outcome measures included demographics, clinical features, age-adjusted incidence, relative survival, overall survival, and distant metastases-free survival. Results: The mean patient age was 61.7 years. Tumour location was choroidal in 82%, ciliochoroidal in 9%, iridociliary in 2%, and iris in 7%. Treatment modalities included brachytherapy (ruthenium-106 and iodine-125 [64%]), enucleation (27%), and proton beam radiation (8%). The mean age-adjusted incidence of uveal melanoma in Ireland from 2010 to 2015 was 9.5 per million of the population (95% confidence interval [CI]: 8.4–10.7). Four-year relative survival was 81.3% (95% CI: 72.8–87.3). Four-year overall survival was 84% (95% CI: 78–90) and 4-year distant metastases-free survival was 79% (95% CI: 73–86). Conclusion: Based on this data, the incidence of uveal melanoma in Ireland is high when compared with other reported incidence rates in Europe and worldwide. Relative and observed survival were in keeping with other reported European survival rates.
Background: Uveal melanoma and its treatment can influence the physical and psychological well-being of patients in a way that differs from other cancers. Factors influencing quality of life (QOL) include visual impairment, changes in appearance, day-to-day functioning, ocular discomfort, and worry regarding disease recurrence. Objective: We aimed to study both general and disease-specific QOL in uveal melanoma patients in Ireland and compare QOL between a plaque radiotherapy group and an enucleation treatment group. This information was sought to enhance our understanding of QOL issues for uveal melanoma patients, in the context of improving care and providing appropriate psychosocial support. Method: The European Organisation for Research and Treatment of Cancer (EORTC) QOL questionnaires QLQ-C30 and QLQ-OPT30 were completed by patients with uveal melanoma treated by enucleation or brachytherapy. Results: 138 of 206 patients completed the questionnaires. There was no significant difference in QOL scores between treatment groups. Thirty-two percent of patients reported concerns about tumour recurrence elsewhere in the body. The brachytherapy group had a significantly higher “role functioning” score (p = 0.030). Enucleation patients were more likely to have problems with appearance (p < 0.0005). Younger patients (12–54 years of age) were more likely to report headaches (p < 0.0005) and problems with reading (p = 0.042), and they had a lower cognitive functioning score (p = 0.003) than those aged ≥55 years. Conclusions: There was no significant difference in reported QOL between treatment groups. Our data identified a number of vulnerable patient subgroups. By anticipating which patients are more likely to suffer in terms of certain aspects of their QOL, we are better able to provide appropriate and timely psychosocial support.
Aim We aim to evaluate the impact of the COVID-19 pandemic on ocular oncology in Ireland, comparing uveal melanoma trends in 2019 to 2020. Methods Patients included for analysis were those that presented to the ocular oncology service from January 2019 to December 2020 in the Royal Victoria Eye and Ear Hospital in Dublin, who underwent primary treatment for uveal melanoma—proton beam therapy, brachytherapy or enucleation. Results Ninety-seven patients presented in 2019 (n = 46) and 2020 (n = 51) who underwent primary treatment for uveal melanoma. Presentation via the eye casualty department was more common in 2020. Dimensions of choroidal melanomas were increased both in basal diameter and thickness compared to those in 2019. More patients had enucleations in 2020 than in 2019 (21.6% vs 9.3%, respectively) and less had proton beam therapy (6.2% vs 12.4%). More patients had evidence of extra-scleral extension at the time of surgery in 2020 compared to 2019 (4.1%, n = 4 versus 0%, respectively). The mean duration of brachytherapy therapy was longer in 2020 (5.3 days ± 35.8) compared to 2019 (4.6 days ± 38.7). Mean time between presentation and primary treatment was 35.6 ± 28.8 days in 2019 and 24.1 ± 20.4 days in 2020. Conclusions More advanced disease is suggested by the increased mean basal diameter and tumour thickness, extra-scleral extension and longer duration of brachytherapy. Time from diagnosis to treatment was not delayed in 2020.
Uveal melanoma (UM) is an intraocular cancer with propensity for liver metastases. The median overall survival (OS) for metastatic UM (MUM) is 1.07 years, with a reported range of 0.84–1.34. In primary UM, high cysteinyl leukotriene receptor 1 (CysLT1) expression associates with poor outcomes. CysLT1 antagonists, quininib and 1,4-dihydroxy quininib, alter cancer hallmarks of primary and metastatic UM cell lines in vitro. Here, the clinical relevance of CysLT receptors and therapeutic potential of quininib analogs is elaborated in UM using preclinical in vivo orthotopic xenograft models and ex vivo patient samples. Immunohistochemical staining of an independent cohort (n = 64) of primary UM patients confirmed high CysLT1 expression significantly associates with death from metastatic disease (p = 0.02; HR 2.28; 95% CI 1.08–4.78), solidifying the disease relevance of CysLT1 in UM. In primary UM samples (n = 11) cultured as ex vivo explants, 1,4-dihydroxy quininib significantly alters the secretion of IL-13, IL-2, and TNF-α. In an orthotopic, cell line-derived xenograft model of MUM, 1,4-dihydroxy quininib administered intraperitoneally at 25 mg/kg significantly decreases ATP5B expression (p = 0.03), a marker of oxidative phosphorylation. In UM, high ATP5F1B is a poor prognostic indicator, whereas low ATP5F1B, in combination with disomy 3, correlates with an absence of metastatic disease in the TCGA-UM dataset. These preclinical data highlight the diagnostic potential of CysLT1 and ATP5F1B in UM, and the therapeutic potential of 1,4-dihydroxy quininib with ATP5F1B as a companion diagnostic to treat MUM.
e21585 Background: The treatment of MUM remains highly unsatisfactory. Single agent ICI produce low response rates. Two recent phase II trials of combination Ipilimumab and Nivolumab yielded response rates of 12% and 18%. We report the long-term survival results of MUM patients (pts) treated with ICI in our institution. Methods: We conducted a retrospective analysis of all pts with a diagnosis of MUM in St Vincent’s University Hospital. Overall survival (OS) was calculated from time of first systemic relapse to death or latest follow-up. One-way ANOVA is used with p < 0.05 considered statistically significant. Results: Out of 244 pts with UM registered in our clinics between April 2008 to October 2020, 52 developed MUM. Median age at initial diagnosis 63 years. 26(50%) are females. Median duration of follow-up of the MUM pts is 35.1 months [2.71-123.2]. Median duration of follow-up from initiation of ICI therapy is 9.1 months [1.6-84.2]. First sites of metastases: liver only 71%, liver plus extrahepatic 17%, and extrahepatic only 12%. Fifteen pts (29%) underwent radical metastasectomy as initial treatment. Thirty-seven (71%) had non-resectable MUM and received systemic treatment (23 total: ICI = 18, chemotherapy = 4, BRAF inhibitors = 1), non-surgical locoregional therapies (5 total: chemosaturation = 3, radiofrequency ablation = 2) or supportive/palliative care (9) as first-line. An additional 22 pts received ICI as second or subsequent treatment, for a total of 40 treated with ICI. Of these, 17 received single agents ICI (Ipilimumab = 11, Pembrolizumab = 6), 13 received sequential Ipilimumab and anti-PD1, and 10 received combination Ipilimumab /Nivolumab. At the time of analysis on 31st October 2020, 9 out of 52 pts (17%) are alive at 2.6, 5.0,5.4,8.9,17.3, 54.7, 77.5, 83.1 and 121.7 months (the 6 longest all had ICI). The median OS is 14.3 months [0.6-121.7]. Pts treated with ICI demonstrated longer OS than pts who did not receive ICI [15.0 months, 5.0-121.7 vs 7.2 months, 0.6-34.6; p = 0.089]. The median OS is 24.9 months (sequential Ipilimumab and anti-PD1) vs 15.0 months (combination Ipilimumab/Nivolumab) vs 13.4 months (single agents). Of the three pts remain alive > 5 years, one is currently disease-free. Conclusions: Prolonged survival beyond five years is achieved by a minority of pts with MUM who receive ICI during their treatment history, although durable initial ICI-induced remission is very rare. Our data suggest that pts who receive two ICI drugs during their illness may have longer survival compared to those who receive only a single ICI.
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