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      Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis

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          Abstract

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          Abstract

          The overall survival (OS) of patients with metastatic uveal melanoma is short, the evidence for effectiveness of treatments is limited, and no consensus on the choice of treatment exists. We aimed to advance interpretation of OS as an outcome by pooling peer-reviewed data. The design is a systematic review and meta-analysis. We searched PubMed from 1 January 1980, to 29 March 2017, for articles reporting patient-level survival in Kaplan–Meier or numerical form. We digitized survival graphs, pooled individual survival times, calculated median OS by treatment modality, and compared each modality by the log-rank test and Cox regression using conventional chemotherapy (CHT) as a reference. Individual-level data were obtained from 78 articles with 2494 patients. The median OS across all treatment modalities was 1.07 years (range: 0.59–2.50 years). Pooled OS reported after isolated hepatic perfusion [median OS: 1.34 years; hazard ratio (HR): 0.92, 95% confidence interval (CI): 0.87–0.97, P = 0.0040], immunoembolization (median OS: 1.63; HR: 0.97, 95% CI: 0.95–1.00, P = 0.0080), and surgery (median OS: 1.43; HR: 0.94, 95% CI: 0.92–0.96, P < 0.0001) was longer, and after checkpoint inhibitor shorter (median OS: 0.59; HR: 1.13, 95% CI: 1.06–1.20, P < 0.0001) than after CHT (median OS: 0.91 years), but subject to identifiable confounding factors. OS following other modalities did not differ from CHT. Reported OS was unassociated with the decade of publication, but depended on the percentage of first-line treated patients. Our results suggest no clinically significant difference in OS by treatment modality or decade. Most of the difference in reported OS likely is attributable to surveillance, selection, and publication bias rather than treatment-related prolongation. Our pooled data provide benchmarks for future trials.

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          Most cited references32

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          Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials.

          Objective tumor response rates observed in phase II trials for metastatic melanoma have historically not provided a reliable indicator of meaningful survival benefits. To facilitate using overall survival (OS) or progression-free survival (PFS) as an endpoint for future phase II trials, we evaluated historical data from cooperative group phase II trials to attempt to develop benchmarks for OS and PFS as reference points for future phase II trials. Individual-level and trial-level data were obtained for patients enrolled onto 42 phase II trials (70 trial arms) that completed accrual in the years 1975 through 2005 and conducted by Southwest Oncology Group, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, North Central Cancer Treatment Group, and the Clinical Trials Group of the National Cancer Institute of Canada. Univariate and multivariate analyses were performed to identify prognostic variables, and between-trial(-arm) variability in 1-year OS rates and 6-month PFS rates were examined. Statistically significant individual-level and trial-level prognostic factors found in a multivariate survival analysis for OS were performance status, presence of visceral disease, sex, and whether the trial excluded patients with brain metastases. Performance status, sex, and age were statistically significant prognostic factors for PFS. Controlling for these prognostic variables essentially eliminated between-trial variability in 1-year OS rates but not in 6-month PFS rates. Benchmarks are provided for 1-year OS or OS curves that make use of the distribution of prognostic factors of the patients in the phase II trial. A similar benchmark for 6-month PFS is provided, but its use is more problematic because of residual between-trial variation in this endpoint.
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            Incidence of uveal melanoma in Europe.

            To estimate incidence rates of uveal melanoma in Europe from 1983 to 1994. Incidence analysis of data from cancer registries adhering to the European Cancer Registry-based study on survival and care of cancer patients (EUROCARE) (cases diagnosed from 1983 to 1994). Data of 6673 patients with ocular melanoma (as defined by International Classification of Diseases for Oncology morphology codes 8720 to 8780 [melanoma] and International Classification of Diseases 9 (ICD9) codes 190.0 [iris and ciliary body], 190.5 [retina], 190.6 [choroid], and 190.9 [unspecified ocular location]) from 33 cancer registries of 16 European countries. Incidence rate ratios (IRRs) were obtained from a multilevel Poisson regression model. Incidence rates and IRRs associated with demographic and geographic variables. Standardized incidence rates increased from south to north across registries, from a minimum of 8 per million in Norway and Denmark. The inclusion of tumors with unspecified ocular location (code 190.9) increased incidence rates in most United Kingdom registries, but not in the other geographic areas, where this code was seldom used for uveal melanomas. Incidence increased noticeably up to age 55 (IRR, 1.46 per 5 years; 95% confidence interval [CI], 1.36-1.57) but leveled off after age 75 (IRR, 0.99 per 5 years; 95% CI, 0.93-1.05), with intermediate levels midway (IRR, 1.18 per 5 years; 95% CI, 1.12-1.23). It was also higher in males (IRR, 1.22; 95% CI, 1.16-1.28). Rates were stable during the study period, but a cohort effect was evidenced, accounting for higher incidence rates in people born during the period 1910 to 1935 (P = 0.005). Incidence increased with latitude (P = 0.008), which explained most differences in rates among areas. In this large series of uveal melanomas, we found stable incidence during the years 1983 to 1994. The north-to-south decreasing gradient supports the protective role of ocular pigmentation. European ophthalmologists should develop guidelines to standardize the coding of tumors treated conservatively using the ICD classification to improve the registration and surveillance of uveal melanoma by cancer registries.
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              Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition

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                Author and article information

                Journal
                Melanoma Res
                Melanoma Res
                MR
                Melanoma Research
                Lippincott Williams & Wilkins
                0960-8931
                1473-5636
                December 2019
                16 January 2019
                : 29
                : 6
                : 561-568
                Affiliations
                Departments of [a ]Ophthalmology, Ocular Oncology Service
                [b ]Oncology, Comprehensive Cancer Centre, Helsinki University Hospital and University of Helsinki, Helsinki
                [c ]Department of Ophthalmology, Etelä-Pohjanmaa Central Hospital, Seinäjoki, Finland
                Author notes
                Correspondence to Elina S. Rantala, MD, Department of Ophthalmology, Helsinki University Hospital, Haartmaninkatu 4 C, PL 220, FI-00029 HUS Helsinki, FinlandTel: +358 947 173 155; fax: +358 947 175 100; e-mail: elina.rantala@ 123456helsinki.fi
                Article
                00001
                10.1097/CMR.0000000000000575
                6887637
                30664106
                e7f1343d-5589-4a72-936f-9b08fd3773b5
                Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 September 2018
                : 21 December 2018
                Categories
                Review Article
                Custom metadata
                TRUE
                T

                melanoma,meta-analysis,metastasis,survival analysis,survival,systematic review,treatment,uveal melanoma,uveal neoplasms

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