Patients presenting with metastases : stage IV uveal melanoma, an international study

Objective To analyse ocular and systemic findings of patients presenting with systemic metastasis. Methods and analysis It is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases. Results Of 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1-T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category. Conclusions Though higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.Peer reviewe

Incidence and Mimickers of Acute Idiopathic Optic Neuritis : Analysis of 291 Consecutive Patients from Southern Finland

Purpose: To estimate the population-based incidence of acute idiopathic optic neuritis (ON) and analyse its differential diagnosis in patients referred with symptoms suggestive of ON. Methods: Patients with suspected ON referred to the Helsinki University Hospital, serving a population of 1.5 million in Southern Finland, were reviewed between 1st May 2008 and 14th April 2012. Brain and optic nerve magnetic resonance imaging (MRI) was performed within 24 hours in 83% of patients. Results: Of 291 referred patients, 184 (63%; 95% confidence interval [CI], 57-69%) were diagnosed with ON whereas 107 (37%) had another condition. The estimated crude incidence of ON in Southern Finland was 3.0 (95% CI 2.8-3.3) per 100,000 (females, 4.6 and males, 1.4). Mean age was 34years (range 15-61), 76% were female. Two (1%) were diagnosed with neuromyelitis optica. ON as the first demyelinative episode was diagnosed in 108 (59%) patients, and MRI showed demyelinating lesions (MRI+) in 82% (95% CI, 75-89) of them. MRI+ predicted the development of multiple sclerosis (MS): 54% of MRI+vs. 5% MRI-patients were diagnosed as MS during a mean follow-up of 7.7years. The most common differential diagnosis was non-arteritic anterior ischemic optic neuropathy (12%). Six (2%) intracranial compressive lesions were found upon MRI scan. Conclusions: More than a third of patients with symptoms suggestive of ON had another condition. Demyelinative lesions on MRI indicated higher risk of developing MS. We recommend the use of MRI to improve the differential diagnostic accuracy of ON and to identify patients with high risk of MS.Peer reviewe

Multicenter, International Assessment of the Eighth Edition of the American Joint Committee on Cancer Cancer Staging Manual for Conjunctival Melanoma

This case series assesses whether the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual can be used to accurately estimate mortality rates of conjunctival melanoma. Key PointsQuestionCan the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for conjunctival melanoma be used to accurately estimate metastasis and mortality rates? FindingsIn this case series of 288 patients, there was a significantly higher cumulative mortality rate among patients with cT2 and cT3 conjunctival melanoma compared with those presenting with cT1 conjunctival melanoma. MeaningHigher T-staged tumors were associated with both an earlier and greater incidence of metastasis; therefore, the results from this multicenter, international registry study support the use of the eighth edition AJCC staging system for conjunctival melanoma. ImportanceEye cancer staging systems used for standardizing patient care and research need to be validated. ObjectiveTo evaluate the accuracy of the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual in estimating metastatis and mortality rates of conjunctival melanoma. Design, Setting, and ParticipantsThis international, multicenter, registry-based case series pooled data from 10 ophthalmic oncology centers from 9 countries on 4 continents. A total of 288 patients diagnosed with conjunctival melanoma from January 1, 2001, to December 31, 2013, were studied. Data analysis was performed from July 7, 2018, to September 11, 2018. InterventionsTreatments included excision biopsy, cryotherapy, topical chemotherapy, radiation therapy, enucleation, and exenteration. Main Outcomes and MeasuresMetastasis rates and 5-year and 10-year Kaplan-Meier mortality rates according to the clinical T categories and subcategories of the eighth edition of the AJCC Cancer Staging Manual. ResultsA total of 288 eyes from 288 patients (mean [SD] age, 59.7 [16.8] years; 147 [51.0%] male) with conjunctival melanoma were studied. Clinical primary tumors (cT) were staged at presentation as cT1 in 218 patients (75.7%), cT2 in 34 (11.8%), cT3 in 15 (5.2%), and cTx in 21 (7.3%). There were no T4 tumors. Pathological T categories (pT) were pTis in 43 patients (14.9%), pT1 in 169 (58.7%), pT2 in 33 (11.5%), pT3 in 12 (4.2%), and pTx in 31 (10.8%). Metastasis at presentation was seen in 5 patients (1.7%). Metastasis during follow-up developed in 24 patients (8.5%) after a median time of 4.3 years (interquartile range, 2.9-6.0 years). Of the 288 patients, 29 died (melanoma-related mortality, 10.1%) at a median time of 5.3 years (interquartile range, 1.8-7.0 years). The cumulative rates of mortality among patients with cT1 tumors were 0% at 1 year, 2.5% (95% CI, 0.7%-7.7%) at 5 years, and 15.2% (95% CI, 8.1%-27.4%) at 10 years of follow-up; among patients with cT2 tumors, 0% at 1 year, 28.6% (95% CI, 12.9%-58.4%) at 5 years, and 43.6% (95% CI, 19.6%-77.9%) at 10 years of follow-up; and among patients with cT3 tumors, 21.1% (95% CI, 8.1%-52.7%) at 1 year of follow-up and 31.6% (95% CI, 13.5%-64.9%) at 5 years of follow-up. Patients with cT2 and cT3 tumors had a significantly higher cumulative mortality rate compared with those presenting with cT1 tumors (log-rank PPeer reviewe

The Global Retinoblastoma Outcome Study : a prospective, cluster-based analysis of 4064 patients from 149 countries

Background Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. Methods We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1,2017, and Dec 31,2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. Findings The cohort included 4064 children from 149 countries. The median age at diagnosis was 23.2 months (IQR 11.0-36.5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0.8%) of 636 children from high-income countries, 55 (5.4%) of 1027 children from upper-middle-income countries, 342 (19. 7%) of 1738 children from lower-middle-income countries, and 196 (42.9%) of 457 children from low-income countries. Enudeation surgery was available for all children and intravenous chemotherapy was available for 4014 (98.8%) of 4064 children. The 3-year survival rate was 99.5% (95% CI 98.8-100.0) for children from high-income countries, 91.2% (89.5-93.0) for children from upper-middle-income countries, 80.3% (78.3-82.3) for children from lower-middle-income countries, and 57.3% (524-63-0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16.67; 95% CI 4.76-50.00), cT4 advanced tumour compared to cT1 (8.98; 4.44-18.18), and older age at diagnosis in children up to 3 years (1.38 per year; 1.23-1.56). For children aged 3-7 years, the mortality risk decreased slightly (p=0.0104 for the change in slope). Interpretation This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma Part I : Metastasis-Associated Mortality

Purpose: To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB). Design: International, multicenter, registry-based retrospective case series. Participants: A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. Methods: Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied. Main Outcome Measures: Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the KaplaneMeier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait. Results: Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year KaplaneMeier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97-99) for cT1b and cT2a, 96% (95% CI, 95-97) for cT2b, 89% (95% CI, 88-90) for cT3 tumors, and 45% (95% CI, 31-59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P <0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastasis in category cT3 (hazard rate [HR], 8.09; 95% CI, 2.55-25.70; P <0.001) and cT4 (HR, 48.55; 95% CI, 12.86-183.27; P <0.001) compared with category cT1. Age, tumor laterality, and presence of heritable traits did not influence the incidence of metastatic disease. Conclusions: Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB. (C) 2020 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND licensePeer reviewe

Use of CNS medications and cognitive decline in the aged: a longitudinal population-based study

<p>Abstract</p> <p>Background</p> <p>Previous studies have found associations between the use of central nervous system medication and the risk of cognitive decline in the aged. Our aim was to assess whether the use of a single central nervous system (CNS) medication and, on the other hand, the combined use of multiple CNS medications over time are related to the risk of cognitive decline in an older (≥ 65 yrs) population that is cognitively intact at baseline.</p> <p>Methods</p> <p>We conducted a longitudinal population-based study of cognitively intact older adults. The participants were 65 years old or older and had Mini-Mental State Examination (MMSE) sum scores of 24 points or higher. The study included a 7.6-year follow-up. The use of benzodiazepines and related drugs (BZDs), antipsychotics (APs), antidepressants (ADs), opioids (Ops), anticholinergics (AChs) and antiepileptics (AEs) was determined at baseline and after a 7.6-years of the follow-up period. Cognitive functioning was used as an outcome variable measured with MMSE at baseline and at the mean follow-up of 7.6 years. Control variables were adjusted with analyses of covariance.</p> <p>Results</p> <p>After adjusting for control variables, the use of Ops and the concomitant use of Ops and BZDs as well as the use of Ops and any CNS medication were associated with cognitive decline. The use of AChs was associated with decline in cognitive functioning only in men.</p> <p>Conclusions</p> <p>Of all the CNS medications analyzed in this study, the use of Ops may have the greatest effect on cognitive functioning in the ageing population. Due to small sample sizes these findings cannot be generalized to the unselected ageing population. More studies are needed concerning the long-term use of CNS medications, especially their concomitant use, and their potential cognitive effects.</p

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. (C) 2016 by the American Academy of Ophthalmology.Peer reviewe

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Incidence and Risk Factors for Secondary Glaucoma in Eyes with Uveal Melanoma

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