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      Combination of Brachytherapy and Intravitreal Chemotherapy in the Treatment of Retinoblastoma with Vitreous Seeding

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          Abstract

          Purpose: The aim of this study was to report the efficacy of combined intravitreal chemotherapy (IVC) and ruthenium-106 brachytherapy in retinoblastoma, either as first-line or second-line treatment, following systemic chemoreduction or intra-arterial chemotherapy. Methods: Retrospective data of 18 eyes from 18 patients treated with IVC and brachytherapy from August 2014 to December 2019 were collected. Results: The method described was our first-line therapy in 6 patients, whereas it was used as second-line treatment after chemoreduction in the remaining 12 patients. The eyes showed the following classification at initial presentation: 2 group B eyes, 3 group C eyes, and 13 group D eyes. The mean follow-up was 19.5 months (range 2–53 months). The mean patient age at brachytherapy was 34.0 months (range 15–83 months). The median prescribed dose at the tumour base and apex was 574.5 ± 306.7 Gy and 88.5 ± 12.2 Gy, respectively. The ocular retention rate was 66.7%. Six eyes had to be enucleated due to uncontrollable subretinal and recurrent vitreous seeding, tumour relapse, recurrence of a solid tumour elsewhere in the eye, and persistent vitreous bleeding with loss of tumour control. The mean number of intravitreal injections of melphalan was 5.0. Two patients received a simultaneous injection of topotecan for insufficient therapeutic response. With regard to radiogenic complications, we could observe temporary retinal and vitreous bleeding (27.8%), serous retinal detachment (44.4%), and radiogenic maculopathy and retinopathy (11.1%). None of the children showed metastatic disease during follow-up. Conclusion: Ruthenium-106 plaque therapy in combination with IVC is an effective local therapy with good tumour control rates even in advanced eyes. Overall, the analysed therapeutic approach shows an acceptable side-effect profile, especially when considering that external-beam radiation therapy and systemic polychemotherapy or at least the number of cycles needed, with their increased incidence of adverse events, can thus be avoided.

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          Most cited references22

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          The American Brachytherapy Society consensus guidelines for plaque brachytherapy of uveal melanoma and retinoblastoma.

          (2014)
          To present the American Brachytherapy Society (ABS) guidelines for plaque brachytherapy of choroidal melanoma and retinoblastoma.
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            The management of retinoblastoma

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              Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications.

              Tumour control of vitreous seeds remains challenging owing to their resistance to radiation and systemic chemotherapy. To describe the short-term efficacy of intravitreal melphalan for vitreous disease in retinoblastoma using a new injection technique and dose. This study is a retrospective non-comparative review of 23 consecutive heavily pretreated patients (23 eyes) with active vitreous seeding and eligible for intravitreous chemotherapy (IViC). They received a total of 122 intravitreal injections of melphalan (20-30 μg) given every 7-10 days. The ocular status was objectively monitored under anaesthesia with fundus photography. All patients are alive without evidence of extraocular spread (95% CI 82.19% to 100%). Concomitant treatments, including other chemotherapeutic modalities, were used until complete sterilisation of the retinal seeding source and subretinal seeds. Globe retention was achieved in 87% (20/23) of cases. All retained eyes were in complete remission after a median follow-up period of 22 months (range 9-31 months). The Kaplan-Meier estimate of ocular survival rates at 2 years was 84.14% (95% CI 62.48% to 95.28%). A localised peripheral salt-and-pepper retinopathy was noted in 10 eyes (43%) at the site of injection. This study reports the first clinically documented case series of patients with retinoblastoma treated with IViC. Despite a possible confounding effect of concomitant chemotherapy prescription using other routes of administration in four of the successfully treated eyes (20%), IViC achieved an unprecedented success rate of tumour control in the presence of vitreous seeding. Of note, none of the treated eyes required external beam irradiation to control the vitreous seeding. Further studies are required to assess IViC retinal toxicity and to better delineate its role in the management of retinoblastoma.
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                Author and article information

                Journal
                OOP
                OOP
                10.1159/issn.2296-4657
                Ocular Oncology and Pathology
                S. Karger AG
                2296-4681
                2296-4657
                2022
                February 2022
                30 November 2021
                : 8
                : 1
                : 64-70
                Affiliations
                [_a] aDepartment of Ophthalmology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
                [_b] bDepartment of Radiotherapy, University Hospital Essen, University Duisburg-Essen, Essen, Germany
                [_c] cDepartment of Paediatric Haematology/Oncology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
                [_d] dDepartment of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany
                Author information
                https://orcid.org/0000-0002-6905-4272
                https://orcid.org/0000-0002-8138-0441
                Article
                520952 Ocul Oncol Pathol 2022;8:64–70
                10.1159/000520952
                41f46ca4-f55d-462f-b06a-288a39d1e2af
                © 2021 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 15 July 2021
                : 15 November 2021
                Page count
                Figures: 2, Tables: 3, Pages: 7
                Categories
                Research Article

                Vision sciences,Ophthalmology & Optometry,Pathology
                Optic neuropathy,Chemoreduction,External-beam radiation therapy,Intravitreal therapy,Radiation maculopathy

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