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      Visual outcome after posterior uveal melanoma episcleral brachytherapy including radiobiological doses

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          Abstract

          Purpose

          To assess the long-term influence of radiobiological doses in the evolution of visual acuity (VA) in patients with uveal melanoma treated by episcleral brachytherapy.

          Material and methods

          Visual acuity was evaluated prospectively from a case series of 243 patients in 2016 treated with 125I. Data analysis was applied to trend VA outcome and find the accurate best-fit line. Biologically effective dose (BED) was included in survival analysis with the use of Kaplan-Meier and Cox regressions. Hazard ratio (HR) and confidence interval at 95% (CI) were determined. Variables statistically significant were analyzed and compared by log-rank tests.

          Results

          The median follow-up was 74.2 months (range, 3-223). Exponential regression shows a 25% reduction and 50% in visual acuity score (VAS) scale for 5 and 27.8 months, respectively. Cumulative probabilities of survival analysis were 57%, 42%, 27%, and 23% at 3, 5, 10, and 15 years, respectively. Multivariable analysis found tumor height (HR = 1.18, 95% CI: 1.07-1.29), applicator size (HR = 1.22, 95% CI: 1.08-1.36), juxtapapillary localization (HR = 1.70, 95% CI: 1.01-2.84), and dose to foveola (HR = 1.01, 95% CI: 1.00-1.01) significantly associated with VA loss. Log-rank tests were significant for all those variables. BED has a strong influence in univariate model, but not statistically significant in the multivariate one.

          Conclusions

          Visual acuity changes can be modeled by an exponential function for the first 5 years after treatment. No relation between VA loss and BED has been found; nevertheless, apical height, plaque size, juxtapapillary localization, and dose to fovea were found as statistical significant variables.

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          Most cited references57

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          Applying Cox regression to competing risks.

          Two methods are given for the joint estimation of parameters in models for competing risks in survival analysis. In both cases Cox's proportional hazards regression model is fitted using a data duplication method. In principle either method can be used for any number of different failure types, assuming independent risks. Advantages of the augmented data approach are that it limits over-parametrisation and it runs immediately on existing software. The methods are used to reanalyse data from two well-known published studies, providing new insights.
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            A practical guide to understanding Kaplan-Meier curves.

            In 1958, Edward L. Kaplan and Paul Meier collaborated to publish a seminal paper on how to deal with incomplete observations. Subsequently, the Kaplan-Meier curves and estimates of survival data have become a familiar way of dealing with differing survival times (times-to-event), especially when not all the subjects continue in the study. "Survival" times need not relate to actual survival with death being the event; the "event" may be any event of interest. Kaplan-Meier analyses are also used in nonmedical disciplines. The purpose of this article is to explain how Kaplan-Meier curves are generated and analyzed. Throughout this article, we will discuss Kaplan-Meier estimates in the context of "survival" before the event of interest. Two small groups of hypothetical data are used as examples in order for the reader to clearly see how the process works. These examples also illustrate the crucially important point that comparative analysis depends upon the whole curve and not upon isolated points. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.
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              21 years of biologically effective dose.

              In 1989 the British Journal of Radiology published a review proposing the term biologically effective dose (BED), based on linear quadratic cell survival in radiobiology. It aimed to indicate quantitatively the biological effect of any radiotherapy treatment, taking account of changes in dose-per-fraction or dose rate, total dose and (the new factor) overall time. How has it done so far? Acceptable clinical results have been generally reported using BED, and it is in increasing use, although sometimes mistaken for "biologically equivalent dose", from which it differs by large factors, as explained here. The continuously bending nature of the linear quadratic curve has been questioned but BED has worked well for comparing treatments in many modalities, including some with large fractions. Two important improvements occurred in the BED formula. First, in 1999, high linear energy transfer (LET) radiation was included; second, in 2003, when time parameters for acute mucosal tolerance were proposed, optimum overall times could then be "triangulated" to optimise tumour BED and cell kill. This occurs only when both early and late BEDs meet their full constraints simultaneously. New methods of dose delivery (intensity modulated radiation therapy, stereotactic body radiation therapy, protons, tomotherapy, rapid arc and cyberknife) use a few large fractions and obviously oppose well-known fractionation schedules. Careful biological modelling is required to balance the differing trends of fraction size and local dose gradient, as explained in the discussion "How Fractionation Really Works". BED is now used for dose escalation studies, radiochemotherapy, brachytherapy, high-LET particle beams, radionuclide-targeted therapy, and for quantifying any treatments using ionising radiation.
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                Author and article information

                Journal
                J Contemp Brachytherapy
                J Contemp Brachytherapy
                JCB
                Journal of Contemporary Brachytherapy
                Termedia Publishing House
                1689-832X
                2081-2841
                30 April 2018
                April 2018
                : 10
                : 2
                : 123-131
                Affiliations
                [1 ]Intraocular Tumors Unit Valladolid University Hospital, Valladolid
                [2 ]University of Valladolid, Valladolid, Spain
                Author notes
                Address for correspondence: David Miguel, MPhys, Hospital Clinico Universitario de Valladolid, C/Avda. Ramón y Cajal s/n, 47003, Valladolid, 47003 Valladolid, Spain. phone: +34 609 96 58 60. e-mail: david.miguel@ 123456outlook.com
                Article
                32735
                10.5114/jcb.2018.75597
                5961527
                29789761
                9ad91737-bb6e-4770-a9ff-aea8335f0a72
                Copyright: © 2018 Termedia Sp. z o. o.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                History
                : 19 January 2018
                : 10 March 2018
                Categories
                Original Paper

                Oncology & Radiotherapy
                brachytherapy,plaque brachytherapy,radiobiology,radiobiological doses,uveal melanoma

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